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complete genome sequence of salmonella enterica serovar typhimurium myophage mushroom.salmonella enterica serovar typhimurium (s. typhimurium) is a leading cause of foodborne illness worldwide. over the past two decades, strains resistant to antibiotics have begun to emerge, highlighting the need for alternative treatment strategies such as bacteriophage therapy. here, we present the complete genome of mushroom, an s. typhimurium myophage.201525858827
salmonella promotes virulence by repressing cellulose production.cellulose is the most abundant organic polymer on earth. in bacteria, cellulose confers protection against environmental insults and is a constituent of biofilms typically formed on abiotic surfaces. we report that, surprisingly, salmonella enterica serovar typhimurium makes cellulose when inside macrophages. we determine that preventing cellulose synthesis increases virulence, whereas stimulation of cellulose synthesis inside macrophages decreases virulence. an attenuated mutant lacking the mgt ...201525848006
bistable expression of csgd in salmonella enterica serovar typhimurium connects virulence to persistence.pathogenic bacteria often need to survive in the host and the environment, and it is not well understood how cells transition between these equally challenging situations. for the human and animal pathogen salmonella enterica serovar typhimurium, biofilm formation is correlated with persistence outside a host, but the connection to virulence is unknown. in this study, we analyzed multicellular-aggregate and planktonic-cell subpopulations that coexist when s. typhimurium is grown under biofilm-in ...201525824832
increased ferroportin-1 expression and rapid splenic iron loss occur with anemia caused by salmonella enterica serovar typhimurium infection in mice.the gram-negative intracellular bacterium salmonella enterica serovar typhimurium causes persistent systemic inflammatory disease in immunocompetent mice. following oral inoculation with s. typhimurium, mice develop a hematopathological syndrome akin to typhoid fever with splenomegaly, microcytic anemia, extramedullary erythropoiesis, and increased hemophagocytic macrophages in the bone marrow, liver, and spleen. additionally, there is marked loss of iron from the spleen, an unanticipated result ...201525824831
characterization of a large novel phage-like plasmid in salmonella enterica serovar typhimurium.salmonella enterica serovar typhimurium is a food-borne pathogen and a leading cause of gastroenteritis in humans. recently, we sequenced a phage-type dt108 strain (l945) and found reads with high similarity to both salmonella typhi strain ct18 plasmid phcm2 and bacteriophage ssu5. in this study, we completely sequenced the novel phage-like plasmid which was designated as pstm_φ. the presence of this phage-like plasmid was examined in a collection of 284 salmonella typhimurium isolates using pcr ...201525795590
ceftriaxone-resistant salmonella enterica serotype typhimurium sequence type 313 from kenyan patients is associated with the blactx-m-15 gene on a novel inchi2 plasmid.multidrug-resistant bacteria pose a major challenge to the clinical management of infections in resource-poor settings. although nontyphoidal salmonella (nts) bacteria cause predominantly enteric self-limiting illness in developed countries, nts is responsible for a huge burden of life-threatening bloodstream infections in sub-saharan africa. here, we characterized nine s. typhimurium isolates from an outbreak involving patients who initially failed to respond to ceftriaxone treatment at a refer ...201525779570
extensive genetic variability linked to is26 insertions in the fljb promoter region of atypical monophasic variants of salmonella enterica serovar typhimurium.fifty-nine monophasic salmonella enterica serovar typhimurium isolates, collected in belgium during the period from 2008 to 2011, have been serotyped as 4,[5]:i:- and shown to harbor an fljb coding sequence. the genetic differences between these strains and phenotypically biphasic salmonella typhimurium were analyzed through pcr and dna sequencing. genetic alterations in the fljb promoter region affecting expression of the phase 2 flagellin were observed in 53 isolates. other genetic events in t ...201525724958
complete genome sequence of salmonella enterica serovar typhimurium siphophage shivani.here, we describe the complete genome sequence of siphophage shivani, a t5-like constituent phage in the therapeutic phage cocktail intestiphage developed for bacterial gastroenteritis. shivani was isolated against a foodborne pathogen, salmonella enterica, which is one of the leading causes of gastroenteritis.201525720685
whole genome sequencing for the retrospective investigation of an outbreak of salmonella typhimurium dt 8.salmonella enterica serovar typhimurium dt8 is uncommon within the european union. an increase in this phage type was reported in the summer of 2013 in the states of jersey.201525713745
extensive amplification of gi-vii-6, a multidrug resistance genomic island of salmonella enterica serovar typhimurium, increases resistance to extended-spectrum cephalosporins.gi-vii-6 is a chromosomally integrated multidrug resistance genomic island harbored by a specific clone of salmonella enterica serovar typhimurium (s.typhimurium). it contains a gene encoding cmy-2 β-lactamase (bla cmy-2), and therefore contributes to extended-spectrum cephalosporin resistance. to elucidate the significance of gi-vii-6 on adaptive evolution, spontaneous mutants of s. typhimurium strain l-3553 were selected on plates containing cefotaxime (ctx). the concentrations of ctx were hig ...201525713569
analysis of the salmonella regulatory network suggests involvement of ssrb and h-ns in σ(e)-regulated spi-2 gene expression.the extracytoplasmic functioning sigma factor σ(e) is known to play an essential role for salmonella enterica serovar typhimurium to survive and proliferate in macrophages and mice. however, its regulatory network is not well-characterized, especially during infection. here we used microarray to identify genes regulated by σ(e) in salmonella grown in three conditions: a nutrient-rich condition and two others that mimic early and late intracellular infection. we found that in each condition σ(e) ...201525713562
stress enhances the sensitivity of salmonella enterica serovar typhimurium to bacteriocins.the aim of this study was to evaluate the potential application of bacteriocins against gram-negative bacteria when associated with others food preservation methods.201525693498
diguanylate cyclase null mutant reveals that c-di-gmp pathway regulates the motility and adherence of the extremophile bacterium acidithiobacillus caldus.an understanding of biofilm formation is relevant to the design of biological strategies to improve the efficiency of the bioleaching process and to prevent environmental damages caused by acid mine/rock drainage. for this reason, our laboratory is focused on the characterization of the molecular mechanisms involved in biofilm formation in different biomining bacteria. in many bacteria, the intracellular levels of c-di-gmp molecules regulate the transition from the motile planktonic state to ses ...201525689133
the bacterial transcription termination factor rho coordinates mg(2+) homeostasis with translational signals.the bacterial protein rho triggers transcription termination at the ends of many operons and when transcription and translation become uncoupled. in addition to these genome wide activities, rho implements regulation of specific genes by dictating whether rna polymerase terminates transcription within the 5' leader region or continues into the downstream coding region. here, we report that the mg(2+) channel gene cora in salmonella enterica serovar typhimurium, which was previously thought to be ...201526523680
allelic variation contributes to bacterial host specificity.understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nssnps) has not been systematically evaluated. here, our genome-wide analysis of core genes within salmonella enterica serovar typhimurium genomes reveals a high ...201526515720
host hydrogen rather than that produced by the pathogen is important for salmonella enterica serovar typhimurium virulence.salmonella enterica serovar typhimurium utilizes molecular hydrogen as a substrate in various respiratory pathways, via h2-uptake enzymes termed hya, hyb, and hyd. a different hydrogenase, the hydrogen-evolving hyc enzyme, removes excess reductant during fermentative growth. virulence phenotypes conferred by mutations in hyc genes, either alone or in combination with mutations in the h2-uptake enzyme genes, are addressed. anaerobically grown δhycb or δhycc single-deletion strains were more sensi ...201525368112
pathogenicity of salmonella strains isolated from egg shells and the layer farm environment in australia.in australia, the egg industry is periodically implicated during outbreaks of salmonella food poisoning. salmonella enterica serovar typhimurium and other nontyphoidal salmonella spp., in particular, are a major concern for australian public health. several definitive types of salmonella typhimurium strains, but primarily salmonella typhimurium definitive type 9 (dt9), have been frequently reported during egg-related food poisoning outbreaks in australia. the aim of the present study was to gene ...201525362057
proteomes of host cell membranes modified by intracellular activities of salmonella enterica.intracellular pathogens need to establish a growth-stimulating host niche for survival and replication. a unique feature of the gastrointestinal pathogen salmonella enterica serovar typhimurium is the creation of extensive membrane networks within its host. an understanding of the origin and function of these membranes is crucial for the development of new treatment strategies. however, the characterization of this compartment is very challenging, and only fragmentary knowledge of its compositio ...201525348832
development of a computational framework for the analysis of protein correlation profiling and spatial proteomics experiments.standard approaches to studying an interactome do not easily allow conditional experiments but in recent years numerous groups have demonstrated the potential for co-fractionation/co-migration based approaches to assess an interactome at a similar sensitivity and specificity yet significantly lower cost and higher speed than traditional approaches. unfortunately, there is as yet no implementation of the bioinformatics tools required to robustly analyze co-fractionation data in a way that can als ...201525464368
two-ball structure of the flagellar hook-length control protein flik as revealed by high-speed atomic force microscopy.the bacterial flagellar hook is a short and uniquely curved tube that connects the basal body to the filament. hook length is controlled at 55 nm on average by a soluble protein flik in salmonella enterica serovar typhimurium. the n-terminal segment of flik responsible for measuring the hook length is considered to be intrinsically disordered. here, we show by high-speed atomic force microscopy that a flik molecule in solution takes on a shape of two balls linked by a flexible string; the larger ...201525463436
natural surface coating to inactivate salmonella enterica serovar typhimurium and maintain quality of cherry tomatoes.the objective of the present study was to investigate the effectiveness of zein-based coatings in reducing populations of salmonella enterica serovar typhimurium and preserving quality of cherry tomatoes. tomatoes were inoculated with a cocktail of s. typhimurium lt2 plus three attenuated strains on the smooth skin surface and stem scar area. the zein-based coatings with and without cinnamon (up to 20%) and mustard essential oil or a commercial wax formulation were applied onto tomatoes and the ...201525462924
transposition and homologous recombination drive evolution of puo-stvr2, a multidrug resistance derivative of pslt, the virulence plasmid specific of salmonella enterica serovar typhimurium.five variants of a resistant derivative of pslt (termed puo-stvr2) were detected in clinical isolates of salmonella enterica serovar typhimurium recovered in spain. the structure of these variants revealed the involvement of is1, is26 and tn21-like transposition, as well as homologous recombination in the generation of deletions, inversions and insertions which, depending on the variant, affected an orf of unknown function, genes encoding a possible iron acquisition system, and/or resistance pro ...201525461846
salmonella enterica: living a double life in epithelial cells.intracellular bacterial pathogens can occupy a membrane-bound vacuole or live freely within the cytosol of mammalian cells. many studies have shown that the enteric bacterium, salmonella enterica serovar typhimurium (s. typhimurium), is a vacuolar pathogen. recent data, however, have revealed that within epithelial cells there are subpopulations of vacuolar and cytosolic salmonella. release from the salmonella-containing vacuole leads to transcriptional reprogramming of bacteria and their robust ...201525461569
genotyping of salmonella enterica serovar typhimurium isolates by multilocus variable number of tandem repeat high-resolution melting analysis (mlv-hrma).salmonella enterica serovar typhimurium (salmonella typhimurium) is one of the most important virulent foodborne pathogens in industrialized countries. the ability to type bacterial strains is essential for surveillance, investigation of outbreaks, and epidemiological studies. multilocus variable number tandem repeat combined with high-resolution melting analysis (mlv-hrma) is a fast, cost-efficient, and easy sample genotyping method. in this study, mlv-hrma and multilocus variable number tandem ...201525457374
cxcl8-l1 and cxcl8-l2 are required in the zebrafish defense against salmonella typhimurium.in recent years zebrafish has emerged as an excellent model for studying the cxcl8 signaling pathway in inflammation elicited upon tissue damage or infection. zebrafish has two true homologs of mammalian cxcl8, named cxcl8-l1 and cxcl8-l2. previously, we have shown that in wound-associated inflammation, these chemokines are up-regulated and are relevant for neutrophil recruitment. in infections, no such knowledge is available as most studies performed on this subject in zebrafish have mainly foc ...201525445910
role of autocleavage in the function of a type iii secretion specificity switch protein in salmonella enterica serovar typhimurium.type iii secretion systems (t3sss) are multiprotein machines employed by many gram-negative bacteria to inject bacterial effector proteins into eukaryotic host cells to promote bacterial survival and colonization. the core unit of t3sss is the needle complex, a supramolecular structure that mediates the passage of the secreted proteins through the bacterial envelope. a distinct feature of the t3ss is that protein export occurs in a strictly hierarchical manner in which proteins destined to form ...201526463164
effect of combined long-term starvation and γ-irradiation on membrane fatty acids and cell surface hydrophobicity of salmonella enterica serovar typhimurium.this study was carried out to explore the adaptive mechanisms of salmonella enterica serovar typhimurium, in particular the implication of fatty acids (fa) in the remodeling of membrane lipid composition to overcome the combined effects of long-term starvation and γ-irradiation stresses. in addition, cell surface hydrophobicity was also evaluated. the bacterial strains (control and starved) were treated with a nonlethal γ-irradiation dose of 0.5 kgy and sublethal doses of 1 kgy. gas chromatograp ...201526433417
enhancement of immunohistochemical detection of salmonella in tissues of experimentally infected pigs.salmonella typhimurium is one of the main pathogens compromising porcine and human health as well as food safety, because it is a prevailing source of foodborne infections due to contaminated pork. a prominent problem in the management of this bacteriosis is the number of subclinically infected carrier pigs. as very little is known concerning the mechanisms allowing salmonella to persist in pigs, the objective of this study was to develop an immunohistochemical approach for the detection of salm ...201526428884
rapid detection of salmonella enterica serovar typhimurium dt104 strains by the polymerase chain reaction.infection with salmonella enterica is a major public health concern in developed countries, and multidrug-resistant strains have become increasingly prevalent. s. enterica serovar typhimurium dt104 (dt104) strains are prevalent in livestock in japan and include numerous strains of multidrug-resistant s. enterica. epidemiological analysis of these strains is critical for both agriculture and public health; however, diagnostic tests for these strains have yielded inconsistent results.201526408088
emergence of vim-1-producing salmonella enterica serovar typhimurium in a paediatric patient. 201526384861
ethanolamine signaling promotes salmonella niche recognition and adaptation during infection.chemical and nutrient signaling are fundamental for all cellular processes, including interactions between the mammalian host and the microbiota, which have a significant impact on health and disease. ethanolamine is an essential component of cell membranes and has profound signaling activity within mammalian cells by modulating inflammatory responses and intestinal physiology. here, we describe a virulence-regulating pathway in which the foodborne pathogen salmonella enterica serovar typhimuriu ...201526565973
rna-seq brings new insights to the intra-macrophage transcriptome of salmonella typhimurium.salmonella enterica serovar typhimurium is arguably the world's best-understood bacterial pathogen. however, crucial details about the genetic programs used by the bacterium to survive and replicate in macrophages have remained obscure because of the challenge of studying gene expression of intracellular pathogens during infection. here, we report the use of deep sequencing (rna-seq) to reveal the transcriptional architecture and gene activity of salmonella during infection of murine macrophages ...201526561851
the arf gtpase-activating protein family is exploited by salmonella enterica serovar typhimurium to invade nonphagocytic host cells.to establish intracellular infections, salmonella bacteria trigger host cell membrane ruffling and invasion by subverting cellular arf guanine nucleotide exchange factors (gefs) that activate arf1 and arf6 gtpases by promoting gtp binding. a family of cellular arf gtpase-activating proteins (gaps) can downregulate arf signaling by stimulating gtp hydrolysis, but whether they do this during infection is unknown. here, we uncovered a remarkable role for distinct arf gap family members in salmonell ...201525670778
toll-like receptor 2 (tlr2) and tlr9 play opposing roles in host innate immunity against salmonella enterica serovar typhimurium infection.toll-like receptors (tlrs) are evolutionarily conserved host proteins that are essential for effective host defense against pathogens. however, recent studies suggest that some tlrs can negatively regulate immune responses. we observed here that tlr2 and tlr9 played opposite roles in regulating innate immunity against oral infection of salmonella enterica serovar typhimurium in mice. while tlr9-/- mice exhibited shortened survival, an increased cytokine storm, and more severe salmonella hepatiti ...201525667264
complete genome of salmonella enterica serovar typhimurium t5-like siphophage stitch.salmonellosis, caused by salmonella, is a leading cause of food poisoning worldwide. with the continuing rise of bacterial antibiotic resistance, efforts are focused on seeking new approaches for treatment of bacterial infections, namely, bacteriophage therapy. here, we report the complete genome of s. typhimurium siphophage stitch.201525657270
gas chromatography-mass spectrometry-based metabolite profiling of salmonella enterica serovar typhimurium differentiates between biofilm and planktonic phenotypes.the aim of this study was to utilize gas chromatography coupled with mass spectrometry (gc-ms) to compare and identify patterns of biochemical change between salmonella cells grown in planktonic and biofilm phases and salmonella biofilms of different ages. our results showed a clear separation between planktonic and biofilm modes of growth. the majority of metabolites contributing to variance between planktonic and biofilm supernatants were identified as amino acids, including alanine, glutamic ...201525636852
flagella-independent surface motility in salmonella enterica serovar typhimurium.flagella are multiprotein complexes necessary for swimming and swarming motility. in salmonella enterica serovar typhimurium, flagella-mediated motility is repressed by the phop/phoq regulatory system. we now report that salmonella can move on 0.3% agarose media in a flagella-independent manner when experiencing the phop/phoq-inducing signal low mg(2+). this motility requires the phop-activated mgta, mgtc, and pagm genes, which specify a mg(2+) transporter, an inhibitor of salmonella's own f1fo ...201525624475
delineating community outbreaks of salmonella enterica serovar typhimurium by use of whole-genome sequencing: insights into genomic variability within an outbreak.whole-genome next-generation sequencing (ngs) was used to retrospectively examine 57 isolates from five epidemiologically confirmed community outbreaks (numbered 1 to 5) caused by salmonella enterica serovar typhimurium phage type dt170. most of the human and environmental isolates confirmed epidemiologically to be involved in the outbreaks were either genomically identical or differed by one or two single nucleotide polymorphisms (snps), with the exception of those in outbreak 1. the isolates f ...201525609719
hydrogen peroxide and hypochlorous acid influx through the major s. typhimurium porin ompd is affected by substitution of key residues of the channel.ompd is the major salmonella enterica serovar typhimurium (s. typhimurium) porin and mediates hydrogen peroxide (h2o2) influx. the results described herein extend this finding to hypochlorous acid (hocl), another reactive oxygen species that is also part of the oxidative burst generated by the phagosome. s. typhimurium cells lacking ompd show decreased hocl influx, and ompd-reconstituted proteoliposomes show an increase in the uptake of the toxic compound. to understand this physiologically rele ...201525600570
plane of nutrition influences the performance, innate leukocyte responses, and resistance to an oral salmonella enterica serotype typhimurium challenge in jersey calves.two experiments investigated how plane of nutrition influences performance, leukocyte responses, and resistance to an oral salmonella enterica serotype typhimurium challenge. in experiment 1, 46 (2±1 d of age) calves were randomly assigned to 2 diets: a low (lpn; n=23) and high plane of nutrition (hpn; n=23). the lpn calves were fed 409 g/d of dry matter (dm) of a 20% crude protein and 20% fat milk replacer, whereas hpn calves were fed 610 and 735 g/d of dm of a 28% crude protein and 25% fat mil ...201525597967
mouse models for assessing the cross-protective efficacy of oral non-typhoidal salmonella vaccine candidates harbouring in-frame deletions of the atp-dependent protease lon and other genes.in balb/c mouse models of salmonella enterica serovar typhimurium infection, a single oral immunization with a mutant strain with an insertion of the chloramphenicol resistance gene into the atp-dependent protease clpp or lon gene decreased the number of salmonellae in each tissue sample 5 days after oral challenge with virulent s. typhimurium at weeks 26 and 54 post-immunization. these data suggested that an oral immunization with the clpp- or lon-disrupted s. typhimurium strain could provide l ...201525589672
repressor activity of the rpos/σs-dependent rna polymerase requires dna binding.the rpos/σ(s) sigma subunit of rna polymerase (rnap) activates transcription of stationary phase genes in many gram-negative bacteria and controls adaptive functions, including stress resistance, biofilm formation and virulence. in this study, we address an important but poorly understood aspect of σ(s)-dependent control, that of a repressor. negative regulation by σ(s) has been proposed to result largely from competition between σ(s) and other σ factors for binding to a limited amount of core r ...201525578965
two-component regulators control hila expression by controlling fimz and hile expression within salmonella enterica serovar typhimurium.salmonellae initiate disease through the invasion of host cells within the intestine. this ability to invade requires the coordinated action of numerous genes, many of which are found within salmonella pathogenicity island 1 (spi-1). the key to this process is the ability of the bacteria to respond to the environment, thereby upregulating the necessary genes under optimal conditions. central to the control of spi-1 is the transcriptional activator hila. work has identified at least 10 different ...201525547794
the frequency and duration of salmonella-macrophage adhesion events determines infection efficiency.salmonella enterica causes a range of important diseases in humans and a in a variety of animal species. the ability of bacteria to adhere to, invade and survive within host cells plays an important role in the pathogenesis of salmonella infections. in systemic salmonellosis, macrophages constitute a niche for the proliferation of bacteria within the host organism. salmonella enterica serovar typhimurium is flagellated and the frequency with which this bacterium collides with a cell is important ...201525533091
plekhm1 regulates salmonella-containing vacuole biogenesis and infection.the host endolysosomal compartment is often manipulated by intracellular bacterial pathogens. salmonella (salmonella enterica serovar typhimurium) secrete numerous effector proteins, including sifa, through a specialized type iii secretion system to hijack the host endosomal system and generate the salmonella-containing vacuole (scv). to form this replicative niche, salmonella targets the rab7 gtpase to recruit host membranes through largely unknown mechanisms. we show that pleckstrin homology d ...201525500191
pathogen detection in complex samples by quartz crystal microbalance sensor coupled to aptamer functionalized core-shell type magnetic separation.a quartz crystal microbalance sensor (qcm) was developed for sensitive and specific detection of salmonella enterica serovar typhimurium cells in food samples by integrating a magnetic bead purification system. although many sensor formats based on bioaffinity agents have been developed for sensitive and specific detection of bacterial cells, the development of robust sensor applications for food samples remained a challenging issue. a viable strategy would be to integrate qcm to a pre-purificat ...201525467500
dissecting the cyclic di-guanylate monophosphate signalling network regulating motility in salmonella enterica serovar typhimurium.flagella-mediated swimming and swarming motility in salmonella enterica serovar typhimurium is intercalated with the cyclic di-guanylate monophosphate (c-di-gmp) signalling network. in this study, we identified the ggdef domain proteins stm2672, stm4551 and stm1987 as key di-guanylate cyclases involved in regulation of motility in a δyhjh phosphodiesterase gene deletion mutant with elevated c-di-gmp levels inhibiting motility. surprisingly, these di-guanylate cyclases distinctively inhibited mot ...201525059628
pathogenicity and phenotypic analysis of sopb, sopd and pipd virulence factors in salmonella enterica serovar typhimurium and salmonella enterica serovar agona.salmonella is an important food-borne pathogen causing disease in humans and animals worldwide. salmonellosis may be caused by any one of over 2,500 serovars of salmonella. nonetheless, salmonella enterica serovar typhimurium and salmonella enterica serovar agona are the second most prevalent serovars isolated from humans and livestock products respectively. limited knowledge is available about the virulence mechanisms responsible for diarrheal disease caused by them. to investigate the contribu ...201525312847
salmonella enterica serovar typhimurium-infected pigs with different shedding levels exhibit distinct clinical, peripheral cytokine and transcriptomic immune response phenotypes.foodborne salmonellosis costs the us $2.7 billion/year, including $100.0 million in annual losses to pork producers. pigs colonized with salmonella are usually asymptomatic with varied severity and duration of fecal shedding. thus, understanding the responses that result in less shedding may provide a mechanism for control. fifty-four pigs were inoculated with salmonella enterica serovar typhimurium (st) and clinical signs, fecal st shedding, growth performance, peripheral cytokines and whole bl ...201524632525
comparative analysis of gene expression: uncovering expression conservation and divergence between salmonella enterica serovar typhimurium strains lt2 and 14028s.different strains of the same organism can share a large amount of their genetic material, the so called core pangenome. nevertheless, these species can display different lifestyles and it is still not well known to what extent the core pangenome plays a role in the divergence of lifestyles between the two organisms. here, we present a procedure for uncovering the conservation and divergence of gene expression by using large expression compendia. we will use data from two salmonella enterica ser ...201525343862
evaluation of the live vaccine efficacy of virulence plasmid-cured, and phop- or aroa-deficient salmonella enterica serovar typhimurium in mice.we evaluated the protective efficacy of 94-kb virulence plasmid-cured, and phop- or aroa-deficient strains of salmonella enterica serovar typhimurium (δphop or δaroa s. typhimurium) as oral vaccine candidates in balb/c mice. two weeks after the completion of 3 oral immunizations with 1 × 10(8) colony-forming units (cfu) of virulence plasmid-cured, and δphop or δaroa s. typhimurium at 10-day intervals, s. typhimurium lipopolysaccharide (lps)-specific mucosal secretory immunoglobulin a (s-iga) ant ...201525341392
a small intestinal organoid model of non-invasive enteric pathogen-epithelial cell interactions.organoids mirror in vivo tissue organization and are powerful tools to investigate the development and cell biology of the small intestine. however, their application for the study of host-pathogen interactions has been largely unexplored. we have established a model using microinjection of organoids to mimic enteric infection, allowing for direct examination of pathogen interactions with primary epithelial cells in the absence of confounding variables introduced by immune cells or the commensal ...201525118165
stress response of salmonella enterica serovar typhimurium to acidified nitrite.the antimicrobial action of the curing agent sodium nitrite (nano2), which is added as a preservative to raw meat products, depends on its conversion to nitric oxide and other reactive nitrogen species under acidic conditions. in this study, we used rna sequencing to analyze the acidified-nano2 shock and adaptive responses of salmonella enterica serovar typhimurium, a frequent contaminant in raw meat, considering parameters relevant for the production of raw-cured sausages. upon a 10-min exposur ...201425107963
interaction of the carbon monoxide-releasing molecule ru(co)3cl(glycinate) (corm-3) with salmonella enterica serovar typhimurium: in situ measurements of carbon monoxide binding by integrating cavity dual-beam spectrophotometry.carbon monoxide (co) is a toxic gas that binds to haems, but also plays critical signalling and cytoprotective roles in mammalian systems; despite problems associated with systemic delivery by inhalation of the gas, it may be employed therapeutically. co delivered to cells and tissues by co-releasing molecules (co-rms) has beneficial and toxic effects not mimicked by co gas; co-rms are also attractive candidates as novel antimicrobial agents. salmonella enterica serovar typhimurium is an enterop ...201425085864
iron at the interface of immunity and infection.both, mammalian cells and microbes have an essential need for iron, which is required for many metabolic processes and for microbial pathogenicity. in addition, cross-regulatory interactions between iron homeostasis and immune function are evident. cytokines and the acute phase protein hepcidin affect iron homeostasis leading to the retention of the metal within macrophages and hypoferremia. this is considered to result from a defense mechanism of the body to limit the availability of iron for e ...201425076907
mucosal inflammatory response to salmonella typhimurium infection.the human intestinal epithelium consists of a single layer of epithelial cells that forms a barrier against food antigens and the resident microbiota within the lumen. this delicately balanced organ functions in a highly sophisticated manner to uphold the fidelity of the intestinal epithelium and to eliminate pathogenic microorganisms. on the luminal side, this barrier is fortified by a thick mucus layer, and on the serosal side exists the lamina propria containing a resident population of immun ...201425071772
the mutagenicity analysis of imidapril hydrochloride and its degradant, diketopiperazine derivative, nitrosation mixtures by in vitro ames test with two strains of salmonella typhimurium.the evaluation of mutagenic properties of imidapril hydrochloride (imd) and its degradation impurity, diketopiperazine derivative (dkp), nitrosation mixtures was conducted in order to analyze the carcinogenic risk of imd long-term treatment in patients. in this study an in vitro ames test with salmonella enterica serovar typhimurium ta 98 and ta 100 strains was used.201425337415
antimicrobial profile of essential oils extracted from wild versus cultivated origanum ehrenberjii against enteric bacteria.the role of origanum ehrenberjii against bacteria that cause enteric diseases is well known. salmonella and enterococcus cause high rates of enteric infections around the world. the aim of this study was to extract essential oils from cultivated and naturally growing o. ehrenberjii, compare the chemical profiles of the extracts and estimate their antimicrobial efficacy against enteric pathogens.201425313614
regulation of salmonella enterica pathogenicity island 1 (spi-1) by the lysr-type regulator leuo.leuo is a quiescent lysr-type regulator belonging to the h-ns regulon. activation of leuo transcription represses expression of pathogenicity island 1 (spi-1) in salmonella enterica serovar typhimurium and inhibits invasion of epithelial cells. loss of hile suppresses leuo-mediated downregulation of spi-1. activation of leuo transcription reduces the level of hild protein, and loss of hile restores the wild type hild level. hence, leuo-mediated downregulation of spi-1 may involve inhibition of h ...201424354910
salmonella exploits nlrp12-dependent innate immune signaling to suppress host defenses during infection.the nucleotide-binding oligomerization domain (nod)-like receptor family pyrin domain containing 12 (nlrp12) plays a protective role in intestinal inflammation and carcinogenesis, but the physiological function of this nlr during microbial infection is largely unexplored. salmonella enterica serovar typhimurium (s. typhimurium) is a leading cause of food poisoning worldwide. here, we show that nlrp12-deficient mice were highly resistant to s. typhimurium infection. salmonella-infected macrophage ...201424347638
salmonella enterica serovar typhimurium infection-induced cd11b+ gr1+ cells ameliorate allergic airway inflammation.allergies are mainly characterized as an unrestrained th2-biased immune response. epidemiological data associate protection from allergic diseases with the exposure to certain infectious agents during early stages of life. modulation of the immune response by pathogens has been considered to be a major factor influencing this protection. recent evidence indicates that immunoregulatory mechanisms induced upon infection ameliorate allergic disorders. a longitudinal study has demonstrated reduced f ...201424343652
.analysis of the contribution of bacteriophage st64b to in vitro virulence traits of salmonella enterica serovar typhimurium.comparison of the publicly available genomes of the virulent salmonella enterica serovar typhimurium (s. typhimurium) strains sl1344, 14028s and d23580 to that of the virulence-attenuated isolate lt2 revealed the absence of a full sequence of bacteriophage st64b in the latter. four selected st64b regions of unknown function (sb7-sb11, sb46, sb49-sb50 and sb54) were mapped by pcr in two strain collections: (i) 310 isolates of s. typhimurium from human blood or stool samples, and from food, animal ...201424324031
structure of a pathogenic type 3 secretion system in action.type 3 secretion systems use 3.5-megadalton syringe-like, membrane-embedded 'injectisomes', each containing an ~800-å-long needle complex to connect intracellular compartments of infectious bacteria and hosts. here we identify requirements for substrate association with, transport through and exit from the injectisome of salmonella enterica serovar typhimurium. this guided the design of substrates that become trapped within the secretion path and enabled visualization of injectisomes in action i ...201424317488
core lipopolysaccharide-specific phage ssu5 as an auxiliary component of a phage cocktail for salmonella biocontrol.salmonella spp. are among the major food-borne pathogens that cause mild diarrhea to severe bacteremia. the use of bacteriophages to control various food-borne pathogens, including salmonella, has emerged as a promising alternative to traditional chemotherapy. we isolated the siphoviridae family phage ssu5, which can infect only rough strains of salmonella. the blocking of ssu5 adsorption by periodate treatment of host salmonella cells and spotting and adsorption assays with mutants that contain ...201424271179
proteomic analysis of intestinal mucosa responses to salmonella enterica serovar typhimurium in naturally infected pig.salmonella enterica serovar typhimurium (s. typhimurium) is one of the most frequent salmonella serotypes isolated from european pigs. despite the advances in understanding the mechanisms involved in host-pathogen interactions and host cell responses to s. typhimurium, the global change that occurs in naturally exposed populations has been poorly characterized. here, we present a proteomics study on intestinal mucosa of pigs naturally infected with s. typhimurium, in order to better understand t ...201424268431
signal-specific temporal response by the salmonella phop/phoq regulatory system.the two-component system phop/phoq controls a large number of genes responsible for a variety of physiological and virulence functions in salmonella enterica serovar typhimurium. here we describe a mechanism whereby the transcriptional activator phop elicits expression of dissimilar gene sets when its cognate sensor phoq is activated by different signals in the periplasm. we determine that full transcription of over half of the genes directly activated by phop requires the mg(2+) transporter mgt ...201424256574
effect of chitosan on salmonella typhimurium in broiler chickens.public concern with the incidence of antibiotic-resistant bacteria, particularly among foodborne pathogens such as salmonella, has been challenging the poultry industry to find alternative means of control. the purposes of the present study were to evaluate in vitro and in vivo effects of chitosan on salmonella enterica serovar typhimurium (st) infection in broiler chicks. for in vitro crop assay experiments, tubes containing feed, water, and st were treated with either saline as a control or 0. ...201424237042
redundancy in the periplasmic adaptor proteins acra and acre provides resilience and an ability to export substrates of multidrug efflux.the components of the acrab-tolc efflux pump function as a tripartite efflux system conferring resistance to multiple antibiotics and the individual components can also function in conjunction with other efflux pumps. this study aimed to establish whether redundancy exists between the homologous periplasmic adaptor proteins (paps) acra and acre and to measure the impact of this redundancy on antimicrobial resistance and the potential efficacy of inhibitor molecules.201424302652
first report of a salmonella enterica serovar typhimurium isolate with carbapenemase (kpc-2) in colombia. 201424295970
a thin-layer chromatography autographic method for the detection of inhibitors of the salmonella phop-phoq regulatory system.the phop-phoq system from salmonella enterica serovar typhimurium controls the expression of factors that are critical for the bacterial entry into host cells and the bacterial intramacrophage survival. therefore it constitutes an interesting target to search for compounds that would control salmonella virulence. localisation of such compounds in complex matrixes could be facilitated by thin-layer chromatography (tlc) bioautography.201424185747
ferric uptake regulator-dependent antinitrosative defenses in salmonella enterica serovar typhimurium pathogenesis.herein we report an important role for the ferric uptake regulator (fur) in the resistance of salmonella enterica serovar typhimurium to the reactive nitrogen species produced by inducible nitric oxide (no) synthase in an nramp1(r) murine model of acute systemic infection. the expression of fur protected salmonella grown under normoxic and hypoxic conditions against the bacteriostatic activity of no. the hypersusceptibility of fur-deficient salmonella to the cytotoxic actions of no coincides wit ...201424166960
dormant intracellular salmonella enterica serovar typhimurium discriminates among salmonella pathogenicity island 2 effectors to persist inside fibroblasts.salmonella enterica uses effector proteins delivered by type iii secretion systems (ttss) to colonize eukaryotic cells. recent in vivo studies have shown that intracellular bacteria activate the ttss encoded by salmonella pathogenicity island-2 (spi-2) to restrain growth inside phagocytes. growth attenuation is also observed in vivo in bacteria colonizing nonphagocytic stromal cells of the intestinal lamina propria and in cultured fibroblasts. spi-2 is required for survival of nongrowing bacteri ...201424144726
extracellular dna inhibits salmonella enterica serovar typhimurium and s. enterica serovar typhi biofilm development on abiotic surfaces.extracellular dna (edna) was identified and characterized in a 2-day-old biofilms developed by salmonella enterica ser. typhimurium sr-11 and s. enterica ser. typhi st6 using confocal laser scanning microscopy (clsm) and enzymatic extraction methods. results of microtitre plate assay and clsm analysis showed both salmonella strains formed significantly more biofilms in the presence of dnase i; furthermore, a remarkable decrease of biofilm formation was observed when edna was added in the inocula ...201424126602
c-jun nh2 -terminal kinase is a critical node in the death of cd4+ cd8+ thymocytes during salmonella enterica serovar typhimurium infection.thymic atrophy, due to the depletion of cd4(+) cd8(+) thymocytes, is observed during infections with numerous pathogens. several mechanisms, such as glucocorticoids and inflammatory cytokines, are known to be involved in this process; however, the roles of intracellular signaling molecules have not been investigated. in this study, the functional role of c-jun nh2 -terminal kinase (jnk) during infection-induced thymic atrophy was addressed. the levels of phosphorylated jnk in immature cd4(+) cd8 ...201424105651
the oxido-reductase enzyme glutathione peroxidase 4 (gpx4) governs salmonella typhimurium-induced neutrophil transepithelial migration.neutrophil (polymorphonuclear leucocytes; pmn) transmigration across mucosal surfaces contributes to dysfunction of epithelial barrier properties, a characteristic underlying many mucosal inflammatory diseases. using salmonella enterica serovar typhimurium (s. typhimurium) as a prototypic proinflammatory insult, we have previously reported that the eicosanoid hepoxilin a3 (hxa3 ), an endogenous product of 12-lipoxygenase (12-lox) activity, is secreted from the apical surface of the intestinal ep ...201424617613
immune response of pigs to salmonella enterica serovar derby and typhimurium infections.interaction between pigs and salmonella enterica serovar derby (salmonella derby) is much less understood in comparison with salmonella enterica serovar typhimurium (salmonella typhimurium). to study interactions of weaned piglets with salmonella derby, we compared the course of infections with salmonella derby de1 and salmonella typhimurium dt104 strains, both isolated from pig herds with a long history of asymptomatic infection. salmonella derby strain used was shed during the 28-day experimen ...201424613290
whole-genome sequences of six salmonella enterica serovar bovismorbificans isolates associated with a 2011 multistate hummus-borne outbreak.we present six draft genome sequences of salmonella enterica serovar bovismorbificans from isolates associated with the 2011 hummus-borne multistate outbreak. all six genome sequences indicate the presence of two plasmids, one of which demonstrates similarity to the 93-kb pslt2 incf-type plasmid of salmonella enterica serovar typhimurium.201424604659
highly specific salt bridges govern bacteriophage p22 icosahedral capsid assembly: identification of the site in coat protein responsible for interaction with scaffolding protein.icosahedral virus assembly requires a series of concerted and highly specific protein-protein interactions to produce a proper capsid. in bacteriophage p22, only coat protein (gp5) and scaffolding protein (gp8) are needed to assemble a procapsid-like particle, both in vivo and in vitro. in scaffolding protein's coat binding domain, residue r293 is required for procapsid assembly, while residue k296 is important but not essential. here, we investigate the interaction of scaffolding protein with a ...201424600011
direct ros scavenging activity of cuep from salmonella enterica serovar typhimurium.salmonella enterica serovar typhimurium (s. typhimurium) is an intracellular pathogen that has evolved to survive in the phagosome of macrophages. the periplasmic copper-binding protein cuep was initially known to confer copper resistance to s. typhimurium. crystal structure and biochemical studies on cuep revealed a putative copper binding site surrounded by the conserved cysteine and histidine residues. a recent study reported that cuep supplies copper ions to periplasmic cu, zn-superoxide dis ...201424598994
sublethal amounts of origanum vulgare l. essential oil and carvacrol cause injury and changes in membrane fatty acid of salmonella typhimurium cultivated in a meat broth.this study aimed to evaluate whether sublethal concentrations of the essential oil of origanum vulgare l. (oveo) and its major compound carvacrol (car) cause injury to the cell membrane and outer membrane of salmonella enterica serovar typhimurium atcc 14028 grown in a meat broth and to assess the effect of these substances on membrane fatty acid (fa) composition. exposure of salmonella typhimurium atcc 14028 to sublethal concentrations of oveo or car caused damage to the cytoplasmic membrane an ...201424588810
conformational changes of the histidine atp-binding cassette transporter studied by double electron-electron resonance spectroscopy.the conformational dynamics of the histidine abc transporter hisqmp2 from salmonella enterica serovar typhimurium, reconstituted into liposomes, is studied by site-directed spin labeling and double electron-electron resonance spectroscopy in the absence of nucleotides, in the atp-bound, and in the post-hydrolysis state. the results show that the inter-dimer distances as measured between the q-loops of hisp2 in the intact transporter resemble those determined for the maltose transporter in all th ...201424583084
il-35-producing b cells are critical regulators of immunity during autoimmune and infectious diseases.b lymphocytes have critical roles as positive and negative regulators of immunity. their inhibitory function has been associated primarily with interleukin 10 (il-10) because b-cell-derived il-10 can protect against autoimmune disease and increase susceptibility to pathogens. here we identify il-35-producing b cells as key players in the negative regulation of immunity. mice in which only b cells did not express il-35 lost their ability to recover from the t-cell-mediated demyelinating autoimmun ...201424572363
the flagellar soluble protein flik determines the minimal length of the hook in salmonella enterica serovar typhimurium.the length of the flagellar hook is controlled by the soluble protein flik. flik is structurally divided into two halves with distinct functions; the n-terminal half determines hook length, while the c-terminal half switches the secretion substrate specificity, consequently terminating hook elongation. flik properly achieves both functions only when it is secreted. in a previous paper, we showed that a temperature-sensitive flge mutant of salmonella enterica serovar typhimurium, sjw2219, produce ...201424563036
novel synergistic approach to exploit the bactericidal efficacy of commercial disinfectants on the biofilms of salmonella enterica serovar typhimurium.combined effect of malic acid and ozone as sanitizer to inhibit the biofilm formation by salmonella typhimurium on different food contact surfaces was investigated in this study. different surfaces used in food industry including pvc pipes, polyethylene bags, plastic surfaces and fresh produce were analyzed for the biofilm formation by s. typhimurium st1 and st2. malic acid alone was not able to inhibit biofilm formation in all the samples. however, combination of malic acid with ozone reduced t ...201424560666
salmonella enterica serovar typhimurium slows down to dodge antibiotics. 201424558352
structure and expression of propanediol utilization microcompartments in acetonema longum.numerous bacteria assemble proteinaceous microcompartments to isolate certain biochemical reactions within the cytoplasm. the assembly, structure, contents, and functions of these microcompartments are active areas of research. here we show that the gram-negative sporulating bacterium acetonema longum synthesizes propanediol utilization (pdu) microcompartments when starved or grown on 1,2-propanediol (1,2-pd) or rhamnose. electron cryotomography of intact cells revealed that pdu microcompartment ...201424532773
experimental salmonellosis challenge model in older calves.non-typhoidal salmonella serovars (nts) are the leading cause of foodborne illnesses worldwide and the leading cause of hospitalization and death due to foodborne illnesses in the united states. while there has been some progress in vaccine development against salmonella spp., there are no broadly protective vaccines. a compounding factor in the development of these vaccines is the lack of a natural model. most vaccine research is performed utilizing a mouse typhoid model. unlike mice, calves in ...201424529790
toll-like receptor-deficient mice reveal how innate immune signaling influences salmonella virulence strategies.pathogens utilize features of the host response as cues to regulate virulence gene expression. salmonella enterica serovar typhimurium (st) sense toll-like receptor (tlr)-dependent signals to induce salmonella pathogenicity island 2 (spi2), a locus required for intracellular replication. to examine pathogenicity in the absence of such cues, we evaluated st virulence in mice lacking all tlr function (tlr2(-/-)xtlr4(-/-)xunc93b1(3d/3d)). when delivered systemically to tlr-deficient mice, st do not ...201424528866
nosocomial outbreak of salmonella enterica serovar typhimurium primarily affecting a pediatric ward in south africa in 2012.we describe a nosocomial outbreak of diarrheal disease caused by extended-spectrum β-lactamase-producing multidrug-resistant salmonella enterica serovar typhimurium, focused on a pediatric ward in south africa. the outbreak peaked between may 2012 and july 2012. person-to-person transmission was the most likely mechanism of spread of the infection, expedited due to a breakdown in hand-washing and hygiene, suboptimal infection control practices, overcrowding of hospital wards, and an undesirable ...201424478499
absence of intestinal pparγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway.to be able to colonize its host, invading salmonella enterica serovar typhimurium must disrupt and severely affect host-microbiome homeostasis. here we report that s. typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (pparγ) expression in intestinal epithelial cells. interestingly, this pparγ down-regulation by s. typhimurium is independent of tlr-4 signaling but triggers a marked elevation of host innate immune response genes, including ...201424465207
fimy of salmonella enterica serovar typhimurium functions as a dna-binding protein and binds the fimz promoter.salmonella enterica serovar typhimurium produces type 1 fimbriae with binding specificity to mannose residues. elements involved in fimbrial structural biosynthesis, transport, and regulation are encoded by the fim gene cluster. fimz, fimy, fimw, stm0551, and an arginine transfer rna (fimu) were previously demonstrated to regulate fimbrial expression. the amino acid sequences of the c-terminal portion of fimy revealed similarity with those of luxr-like proteins. electrophoretic mobility shift as ...201424462182
female partner preferences enhance offspring ability to survive an infection.it is often suggested that mate choice enhances offspring immune resistance to infectious diseases. to test this hypothesis, we conducted a study with wild-derived house mice (mus musculus musculus) in which females were experimentally mated either with their preferred or non-preferred male, and their offspring were infected with a mouse pathogen, salmonella enterica (serovar typhimurium).201424450606
neutrophils are a source of gamma interferon during acute salmonella enterica serovar typhimurium colitis.gamma interferon (ifn-γ) is an important driver of intestinal inflammation during colitis caused by salmonella enterica serovar typhimurium. here we used the mouse colitis model to investigate the cellular sources of ifn-γ in the cecal mucosa during the acute phase of an s. typhimurium infection. while ifn-γ staining was detected in t cells, nk cells, and inflammatory monocytes at 2 days after infection, the majority of ifn-γ-positive cells in the cecal mucosa were neutrophils. furthermore, neut ...201424421037
bacterial flagellin-specific chaperone flis interacts with anti-sigma factor flgm.flagella are extracellular organelles that propel bacteria. each flagellum consists of a basal body, a hook, and a filament. the major protein of the filament is flagellin. induction of flagellin gene expression coincides with secretion of flgm. the role of flgm is to inhibit flia (σ(28)), a flagellum-specific rna polymerase responsible for flagellin transcription. to prevent premature polymerization of newly synthesized flagellin molecules, flis, the flagellin-specific chaperone, binds flagelli ...201424415724
the role of the st313-td gene in virulence of salmonella typhimurium st313.multidrug-resistant salmonella enterica serovar typhimurium st313 has emerged in sub-saharan africa causing severe infections in humans. therefore, it has been speculated that this specific sequence type, st313, carries factors associated with increased pathogenicity. we assessed the role in virulence of a gene with a yet unknown function, st313-td, detected in st313 through comparative genomics. additionally, the structure of the genomic island st313-gi, harbouring the gene was determined. the ...201424404174
ttss2-deficient hha mutant of salmonella typhimurium exhibits significant systemic attenuation in immunocompromised hosts.non-typhoidal salmonella (nts) infections are emerging as leading problem worldwide and the variations in host immune status append to the concern of nts. salmonella enterica serovar typhimurium is one of the causative agents of nts infections and has been extensively studied. the inactivation of salmonella pathogenicity island 2 (spi2) encoded type-iii secretion system 2 (ttss2) has been reported rendering the strain incapable for systemic dissemination to host sites and has also been proposed ...201424401482
outbreak of salmonellosis associated with consumption of pulled pork at a church festival - hamilton county, ohio, 2010.on june 18, 2010, hamilton county public health (hcph), a local health department in ohio, began receiving reports of gastrointestinal illness from persons who attended a church festival held during june 11-13 in a suburban community of hamilton county. hcph investigated and confirmed the existence of a foodborne outbreak associated with consumption of pulled pork prepared in a private home and sold at the church festival. sixty-four attendees with gastroenteritis were identified. salmonella ent ...201424381078
iron-induced virulence of salmonella enterica serovar typhimurium at the intestinal epithelial interface can be suppressed by carvacrol.oral iron therapy can increase the abundance of bacterial pathogens, e.g., salmonella spp., in the large intestine of african children. carvacrol is a natural compound with antimicrobial activity against various intestinal bacterial pathogens, among which is the highly prevalent salmonella enterica serovar typhimurium. this study aimed to explore a presumed interaction between carvacrol and bacterial iron handling and to assess the potential of carvacrol in preventing the increase of bacterial p ...201424379194
differential timing of antibody-mediated phagocytosis and cell-free killing of invasive african salmonella allows immune evasion.nontyphoidal salmonellae commonly cause fatal bacteraemia in african children lacking anti-salmonella antibodies. these are facultative intracellular bacteria capable of cell-free and intracellular survival within macrophages. to better understand the relationship between extracellular and intracellular infection in blood and general mechanisms of ab-related protection against salmonella, we used human blood and sera to measure kinetics of ab and complement deposition, serum-mediated bactericida ...201424375424
identification of hild-regulated genes in salmonella enterica serovar typhimurium.salmonella enterica serovar typhimurium (s. typhimurium) pathogenicity island 1 (spi-1) encodes a type iii secretion system required for invasion of host gut epithelial cells. expression of spi-1 virulence genes is controlled by a complex hierarchy of transcription factors encoded within and outside spi-1. the master regulator of spi-1, hila, is itself regulated by three homologous transcription factors, hild, hilc, and rtsa. hild activates transcription of hila and other target genes in respons ...201424375101
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