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antimicrobial activities of fidaxomicin.fidaxomicin is bactericidal against clostridium difficile. the combined results of 8 in vitro studies of 1323 c. difficile isolates showed the minimum inhibitory concentration (mic) range of fidaxomicin to be ≤ 0.001-1 μg/ml, with a maximum mic for inhibition of 90% of organisms (mic(90)) of 0.5 μg/ml. isolates from 2 phase iii clinical trials demonstrated that fidaxomicin mics of baseline isolates did not predict clinical cure, failure, or recurrence of c. difficile infections. no resistance to ...201222752863
first comprehensive evaluation of the m.i.c. evaluator device compared to etest and clsi reference dilution methods for antimicrobial susceptibility testing of clinical strains of anaerobes and other fastidious bacterial species.the new m.i.c. evaluator strip uses test methodology and the recording of results that are similar to those of etest. for this first assessment, 102 clinical strains of anaerobic bacteria from 12 genera and 155 strains from 7 genera and 8 species of fastidious bacteria were tested by m.i.c. evaluator, etest, and agar dilution or broth microdilution as a reference standard. ampicillin, amoxicillin, amoxicillin-clavulanate, cefotaxime, ciprofloxacin, erythromycin, imipenem, levofloxacin, metronida ...201222238439
a preliminary study of pneumonia etiology among hospitalized children in kenya.pneumonia is the leading cause of childhood death in the developing world. higher-quality etiological data are required to reduce this mortality burden.201222403235
antibacterial and antifungal activities of new acylated derivatives of epigallocatechin gallate.(-)-epigallocatechin-3-o-gallate (egcg) has useful antiviral, antimicrobial, antitoxin, and antitumor properties. previously, mori et al. (2008) found that addition of long acyl chains (c16-18) to egcg enhanced its anti-influenza virus activity up to 44-fold. the chemical stability of egcg against oxidative degradation was also enhanced by acylation. we further evaluated the in vitro activity spectrum of the egcg derivatives against a wide range of bacteria and fungi. a series of egcg o-acyl der ...201222355295
competition for zinc binding in the host-pathogen interaction.due to its favorable chemical properties, zinc is used as a structural or catalytic cofactor in a very large number of proteins. despite the apparent abundance of this metal in all cell types, the intracellular pool of loosely bound zinc ions available for biological exchanges is in the picomolar range and nearly all zinc is tightly bound to proteins. in addition, to limit bacterial growth, some zinc-sequestering proteins are produced by eukaryotic hosts in response to infections. therefore, to ...201324400228
recognition of extracellular bacteria by nlrs and its role in the development of adaptive immunity.innate immune recognition of bacteria is the first requirement for mounting an effective immune response able to control infection. over the previous decade, the general paradigm was that extracellular bacteria were only sensed by cell surface-expressed toll-like receptors (tlrs), whereas cytoplasmic sensors, including members of the nod-like receptor (nlr) family, were specific to pathogens capable of breaching the host cell membrane. it has become apparent, however, that intracellular innate i ...201324155747
strategy for sensitive and specific detection of yersinia pestis in skeletons of the black death pandemic.yersinia pestis has been identified as the causative agent of the black death pandemic in the 14(th) century. however, retrospective diagnostics in human skeletons after more than 600 years are critical. we describe a strategy following a modern diagnostic algorithm and working under strict ancient dna regime for the identification of medieval human plague victims. an initial screening and dna quantification assay detected the y. pestis specific pla gene of the high copy number plasmid ppcp1. re ...201324069445
broad-spectrum biosensor capable of detecting and identifying diverse bacterial and candida species in blood.we describe an assay which uses broad-spectrum, conserved-site pcr paired with mass spectrometry analysis of amplicons (pcr/electrospray ionization-mass spectrometry [esi-ms]) to detect and identify diverse bacterial and candida species in uncultured specimens. the performance of the assay was characterized using whole-blood samples spiked with low titers of 64 bacterial species and 6 candida species representing the breadth of coverage of the assay. the assay had an average limit of detection o ...201323761152
causal inference regarding infectious aetiology of chronic conditions: a systematic review.the global burden of disease has shifted from communicable diseases in children to chronic diseases in adults. this epidemiologic shift varies greatly by region, but in europe, chronic conditions account for 86% of all deaths, 77% of the disease burden, and up to 80% of health care expenditures. a number of risk factors have been implicated in chronic diseases, such as exposure to infectious agents. a number of associations have been well established while others remain uncertain.201323935899
bacteria in the nose of young adults during wellness and rhinovirus colds: detection by culture and microarray methods in 100 nasal lavage specimens.patients  with  viral respiratory infections/viral rhinitis/common colds are often treated with antibiotic; however, there is little information on whether or how bacterial microbiota in the nose and nasopharynx might influence the course of viral illnesses.201323801660
comprehensive antigen screening identifies moraxella catarrhalis proteins that induce protection in a mouse pulmonary clearance model.moraxella catarrhalis is one of the three most common causative bacterial pathogens of otitis media, however no effective vaccine against m. catarrhalis has been developed so far. to identify m. catarrhalis vaccine candidate antigens, we used carefully selected sera from children with otitis media and healthy individuals to screen small-fragment genomic libraries that are expressed to display frame-selected peptides on a bacterial cell surface. this antigenome technology led to the identificatio ...201323671716
rapid pcr detection of mycoplasma hominis, ureaplasma urealyticum, and ureaplasma parvum.objective. we compared laboratory developed real-time pcr assays for detection of mycoplasma hominis and for detection and differentiation of ureaplasma urealyticum and parvum to culture using genitourinary specimens submitted for m. hominis and ureaplasma culture. methods. 283 genitourinary specimens received in the clinical bacteriology laboratory for m. hominis and ureaplasma species culture were evaluated. nucleic acids were extracted using the total nucleic acid kit on the magna pure 2.0. 5 ...201326904723
the k1 capsular polysaccharide from acinetobacter baumannii is a potential therapeutic target via passive immunization.the emergence of extremely resistant and panresistant gram-negative bacilli, such as acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. the goal of this report was to evaluate the k1 capsular polysaccharide from a. baumannii as a passive immunization target. its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (nmr) techniques. molecular mimics that might raise the concern for autoimmune disease were not ident ...201323297385
real-time comparative evaluation of biomerieux vitek ms versus bruker microflex ms, two matrix-assisted laser desorption-ionization time-of-flight mass spectrometry systems, for identification of clinically significant bacteria.matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (maldi-tof ms) recently became available for the identification of bacteria in routine diagnostic laboratories. it is rapid and cost-effective and likely to replace phenotypic identification. this study was undertaken to compare two maldi-tof ms-based, bruker microflex ms (bms) and vitek ms (vms) systems, for identification (id) of clinically significant bacterial isolates. clinically relevant broad diversity of bacteri ...201425433488
antibacterial activity and mode of action of selected glucosinolate hydrolysis products against bacterial pathogens.plants contain numerous components that are important sources of new bioactive molecules with antimicrobial properties. isothiocyanates (itcs) are plant secondary metabolites found in cruciferous vegetables that are arising as promising antimicrobial agents in food industry. the aim of this study was to assess the antibacterial activity of two isothiocyanates (itcs), allylisothiocyanate (aitc) and 2-phenylethylisothiocyanate (peitc) against escherichia coli, pseudomonas aeruginosa, staphylococcu ...201426243895
antibacterial activity and mode of action of selected glucosinolate hydrolysis products against bacterial pathogens.plants contain numerous components that are important sources of new bioactive molecules with antimicrobial properties. isothiocyanates (itcs) are plant secondary metabolites found in cruciferous vegetables that are arising as promising antimicrobial agents in food industry. the aim of this study was to assess the antibacterial activity of two isothiocyanates (itcs), allylisothiocyanate (aitc) and 2-phenylethylisothiocyanate (peitc) against escherichia coli, pseudomonas aeruginosa, staphylococcu ...201426243895
the yersinia pestis siderophore, yersiniabactin, and the znuabc system both contribute to zinc acquisition and the development of lethal septicaemic plague in mice.bacterial pathogens must overcome host sequestration of zinc (zn(2+) ), an essential micronutrient, during the infectious disease process. while the mechanisms to acquire chelated zn(2+) by bacteria are largely undefined, many pathogens rely upon the znuabc family of abc transporters. here we show that in yersinia pestis, irp2, a gene encoding the synthetase (hmwp2) for the siderophore yersiniabactin (ybt) is required for growth under zn(2+) -deficient conditions in a strain lacking znuabc. more ...201424979062
3,4-dhpea-ea from olea europaea l. is effective against standard and clinical isolates of staphylococcus sp.the aim of the present work was to evaluate the antibacterial effect of 3,4-dhpea-ea (methyl-4-(2-(3,4-dihydroxyphenethoxy)-2-oxoethyl)-3-formyl-2-methyl-3,4-dihydro-2h-pyran-5-carboxylate), a derivate of oleuropein, against a range of gram-positive bacteria, including atcc strains, food and clinical isolates.201424986240
carbohydrate-mimetic peptides for pan anti-tumor responses.molecular mimicry is fundamental to biology and transcends to many disciplines ranging from immune pathology to drug design. structural characterization of molecular partners has provided insight into the origins and relative importance of complementarity in mimicry. chemical complementarity is easy to understand; amino acid sequence similarity between peptides, for example, can lead to cross-reactivity triggering similar reactivity from their cognate receptors. however, conformational complemen ...201425071769
high-throughput sequencing for the study of bacterial pathogen biology.a revolution in sequencing technologies in recent years has led to dramatically increased throughput and reduced cost of bacterial genome sequencing. an increasing number of applications of the new technologies are providing broad insights into bacterial evolution, epidemiology, and pathogenesis. for example, the capacity to sequence large numbers of bacterial isolates is enabling high resolution phylogenetic analyses of bacterial populations leading to greatly enhanced understanding of the emer ...201425033019
nitropropenyl benzodioxole, an anti-infective agent with action as a protein tyrosine phosphatase inhibitor.we report on the activities of a broad spectrum antimicrobial compound,nitropropenyl benzodioxole (npbd) which are of relevance to its potential as an anti-infective drug. these investigations support the proposal that a major mechanism of npbd is action as a tyrosine mimetic, competitively inhibiting bacterial and fungal protein tyrosine phosphatases (ptp). npbd did not affect major anti-bacterial drug targets, namely, atp production, cell wall or cell membrane integrity, or transcription and t ...201424976873
proteomics of aggregatibacter actinomycetemcomitans outer membrane vesicles.aggregatibacter actinomycetemcomitans is an oral and systemic pathogen associated with aggressive forms of periodontitis and with endocarditis. outer membrane vesicles (omvs) released by this species have been demonstrated to deliver effector proteins such as cytolethal distending toxin (cdt) and leukotoxin (ltxa) into human host cells and to act as triggers of innate immunity upon carriage of nod1- and nod2-active pathogen-associated molecular patterns (pamps). to improve our understanding of t ...201526381655
haemophilus influenzae: using comparative genomics to accurately identify a highly recombinogenic human pathogen.haemophilus influenzae is an opportunistic bacterial pathogen that exclusively colonises humans and is associated with both acute and chronic disease. despite its clinical significance, accurate identification of h. influenzae is a non-trivial endeavour. h. haemolyticus can be misidentified as h. influenzae from clinical specimens using selective culturing methods, reflecting both the shared environmental niche and phenotypic similarities of these species. on the molecular level, frequent geneti ...201526311542
aptamers against pathogenic microorganisms.an important current issue of modern molecular medicine and biotechnology is the search for new approaches to early diagnostic assays and adequate therapy of infectious diseases. one of the promising solutions to this problem might be a development of nucleic acid aptamers capable of interacting specifically with bacteria, protozoa, and viruses. such aptamers can be used for the specific recognition of infectious agents as well as for blocking of their functions. the present review summarizes va ...201526258445
aptamers against pathogenic microorganisms.an important current issue of modern molecular medicine and biotechnology is the search for new approaches to early diagnostic assays and adequate therapy of infectious diseases. one of the promising solutions to this problem might be a development of nucleic acid aptamers capable of interacting specifically with bacteria, protozoa, and viruses. such aptamers can be used for the specific recognition of infectious agents as well as for blocking of their functions. the present review summarizes va ...201526258445
development of a multilocus sequence typing scheme for molecular typing of mycoplasma pneumoniae.mycoplasma pneumoniae is a major human respiratory pathogen causing both upper and lower respiratory disease in humans of all ages, and it can also result in other serious extrapulmonary sequelae. a multilocus sequence typing (mlst) scheme for m. pneumoniae was developed based on the sequences of eight housekeeping genes (ppa, pgm, gyrb, gmk, glya, atpa, arcc, and adk) and applied to 55 m. pneumoniae clinical isolates and the two type strains m129 and fh. a total of 12 sequence types (sts) resul ...201526202118
structural basis of transcription inhibition by cbr hydroxamidines and cbr pyrazoles.cbr hydroxamidines are small-molecule inhibitors of bacterial rna polymerase (rnap) discovered through high-throughput screening of synthetic-compound libraries. cbr pyrazoles are structurally related rnap inhibitors discovered through scaffold hopping from cbr hydroxamidines. cbr hydroxamidines and pyrazoles selectively inhibit gram-negative bacterial rnap and exhibit selective antibacterial activity against gram-negative bacteria. here, we report crystal structures of the prototype cbr hydroxa ...201526190576
biological properties of extracellular vesicles and their physiological functions.in the past decade, extracellular vesicles (evs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. this is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. while intensive investigation has targeted the role of evs in different pathological processes, for example, in cancer and autoimmune diseases, the ev-mediated ...201525979354
moraxella catarrhalis acrab-oprm efflux pump contributes to antimicrobial resistance and is enhanced during cold shock response.moraxella catarrhalis is a common pathogen of the human respiratory tract. multidrug efflux pumps play a major role in antibiotic resistance and virulence in many gram-negative organisms. in the present study, the role of the acrab-oprm efflux pump in antibiotic resistance was investigated by constructing mutants that lack the acra, acrb, and oprm genes in m. catarrhalis strain o35e. we observed a moderate (1.5-fold) decrease in the mics of amoxicillin and cefotaxime and a marked (4.7-fold) decr ...201525583725
the capricious nature of bacterial pathogens: phasevarions and vaccine development.infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. one of the key considerations for rational vaccine development is the selection of appropriate antigens. antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. antigens with variable expression, due ...201628018352
mechanisms of outer membrane vesicle entry into host cells.bacterial outer membrane vesicles (omvs) are nano-sized compartments consisting of a lipid bilayer that encapsulates periplasm-derived, luminal content. omvs, which pinch off of gram-negative bacteria, are now recognized as a generalized secretion pathway which provides a means to transfer cargo to other bacterial cells as well as eukaryotic cells. compared with other secretion systems, omvs can transfer a chemically extremely diverse range of cargo, including small molecules, nucleic acids, pro ...201627529760
development of a fast and low-cost qpcr assay for diagnosis of acute gas pharyngitis.group a streptococci (gas) are the most common bacterial cause of acute pharyngitis and account for 15-30 % of cases of acute pharyngitis in children and 5-10 % of cases in adults. in this study, a real-time quantitative pcr (qpcr) based gas detection assay in pharyngeal swab specimens was developed.201627501688
evaluation of an automated system for reading and interpreting disk diffusion antimicrobial susceptibility testing of fastidious bacteria.results of disk diffusion antimicrobial susceptibility testing depend on individual visual reading of inhibition zone diameters. therefore, automated reading using camera systems might represent a useful tool for standardization. in this study, the adagio automated system (bio-rad) was evaluated for reading disk diffusion tests of fastidious bacteria. 144 clinical isolates (68 β-haemolytic streptococci, 28 streptococcus pneumoniae, 18 viridans group streptococci, 13 haemophilus influenzae, 7 mor ...201627391898
comparative analysis of prophage-like elements in helicobacter sp. genomes.prophages are regarded as one of the factors underlying bacterial virulence, genomic diversification, and fitness, and are ubiquitous in bacterial genomes. information on helicobacter sp. prophages remains scarce. in this study, sixteen prophages were identified and analyzed in detail. eight of them are described for the first time. based on a comparative genomic analysis, these sixteen prophages can be classified into four different clusters. phylogenetic relationships of cluster a helicobacter ...201627169002
rapid 16s rrna next-generation sequencing of polymicrobial clinical samples for diagnosis of complex bacterial infections.classifying individual bacterial species comprising complex, polymicrobial patient specimens remains a challenge for culture-based and molecular microbiology techniques in common clinical use. we therefore adapted practices from metagenomics research to rapidly catalog the bacterial composition of clinical specimens directly from patients, without need for prior culture. we have combined a semiconductor deep sequencing protocol that produces reads spanning 16s ribosomal rna gene variable regions ...201323734239
oligotyping analysis of the human oral microbiome.the human microbiome project provided a census of bacterial populations in healthy individuals, but an understanding of the biomedical significance of this census has been hindered by limited taxonomic resolution. a high-resolution method termed oligotyping overcomes this limitation by evaluating individual nucleotide positions using shannon entropy to identify the most information-rich nucleotide positions, which then define oligotypes. we have applied this method to comprehensively analyze the ...201424965363
epigenetics and bacterial infections.epigenetic mechanisms regulate expression of the genome to generate various cell types during development or orchestrate cellular responses to external stimuli. recent studies highlight that bacteria can affect the chromatin structure and transcriptional program of host cells by influencing diverse epigenetic factors (i.e., histone modifications, dna methylation, chromatin-associated complexes, noncoding rnas, and rna splicing factors). in this article, we first review the molecular bases of the ...201223209181
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new antimicrobial agents approved by the u.s. food and drug administration in 1997 and new indications for previously approved agents. 19989559830
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adhesins involved in attachment to abiotic surfaces by gram-negative bacteria.during the first step of biofilm formation, initial attachment is dictated by physicochemical and electrostatic interactions between the surface and the bacterial envelope. depending on the nature of these interactions, attachment can be transient or permanent. to achieve irreversible attachment, bacterial cells have developed a series of surface adhesins promoting specific or nonspecific adhesion under various environmental conditions. this article reviews the recent advances in our understandi ...201526350310
the relationship between extensively drug-resistant tuberculosis and multidrug-resistant gram-negative bacilli.the relationship between extensively drug-resistant tuberculosis (xdr-tb) and multidrug-resistant gram-negative bacilli (mdr-gnb) is unclear. identification of the relationship between xdr-tb and mdr-gnb would have important implications for patient care.201526230499
new target for inhibition of bacterial rna polymerase: 'switch region'.a new drug target - the 'switch region' - has been identified within bacterial rna polymerase (rnap), the enzyme that mediates bacterial rna synthesis. the new target serves as the binding site for compounds that inhibit bacterial rna synthesis and kill bacteria. since the new target is present in most bacterial species, compounds that bind to the new target are active against a broad spectrum of bacterial species. since the new target is different from targets of other antibacterial agents, com ...201121862392
challenges and future prospects of antibiotic therapy: from peptides to phages utilization.bacterial infections are raising serious concern across the globe. the effectiveness of conventional antibiotics is decreasing due to global emergence of multi-drug-resistant (mdr) bacterial pathogens. this process seems to be primarily caused by an indiscriminate and inappropriate use of antibiotics in non-infected patients and in the food industry. new classes of antibiotics with different actions against mdr pathogens need to be developed urgently. in this context, this review focuses on seve ...201424860506
type iv pilin proteins: versatile molecular modules.type iv pili (t4p) are multifunctional protein fibers produced on the surfaces of a wide variety of bacteria and archaea. the major subunit of t4p is the type iv pilin, and structurally related proteins are found as components of the type ii secretion (t2s) system, where they are called pseudopilins; of dna uptake/competence systems in both gram-negative and gram-positive species; and of flagella, pili, and sugar-binding systems in the archaea. this broad distribution of a single protein family ...201223204365
common cell shape evolution of two nasopharyngeal pathogens.respiratory infectious diseases are the third cause of worldwide death. the nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as neisseria meningitidis and moraxella catarrhalis. these microbes possess several surface structures that interact with the actors of the innate immune system. in our attempt to understand the past evolution of these bacteria and their adaption to the nasopharynx, we first studied differences ...201526162030
origin of the diversity in dna recognition domains in phasevarion associated moda genes of pathogenic neisseria and haemophilus influenzae.phase variable restriction-modification (r-m) systems have been identified in a range of pathogenic bacteria. in some it has been demonstrated that the random switching of the mod (dna methyltransferase) gene mediates the coordinated expression of multiple genes and constitutes a phasevarion (phase variable regulon). moda of neisseria and haemophilus influenzae contain a highly variable, dna recognition domain (drd) that defines the target sequence that is modified by methylation and is used to ...201222457715
how old are bacterial pathogens?only few molecular studies have addressed the age of bacterial pathogens that infected humans before the beginnings of medical bacteriology, but these have provided dramatic insights. the global genetic diversity of helicobacter pylori, which infects human stomachs, parallels that of its human host. the time to the most recent common ancestor (tmrca) of these bacteria approximates that of anatomically modern humans, i.e. at least 100 000 years, after calibrating the evolutionary divergence withi ...201627534956
where does neisseria acquire foreign dna from: an examination of the source of genomic and pathogenic islands and the evolution of the neisseria genus.pathogenicity islands (pais) or genomic islands (geis) are considered to be the result of a recent horizontal transfer. detecting pais/geis as well as their putative source can provide insight into the organism's pathogenicity within its host. previously we introduced a tool called s-plot which provides a visual representation of the variation in compositional properties across and between genomic sequences. utilizing s-plot and new functionality developed here, we examined 18 publicly available ...201324007216
a critical role for the ccca gene product, cytochrome c2, in diverting electrons from aerobic respiration to denitrification in neisseria gonorrhoeae.neisseria gonorrhoeae is a microaerophile that, when oxygen availability is limited, supplements aerobic respiration with a truncated denitrification pathway, nitrite reduction to nitrous oxide. we demonstrate that the ccca gene of neisseria gonorrhoeae strain f62 (accession number ng0292) is expressed, but the product, cytochrome c2, accumulates to only low levels. nevertheless, a ccca mutant reduced nitrite at about half the rate of the parent strain. we previously reported that cytochromes c4 ...201323543713
potential use of atlantic cod trypsin in biomedicine.surface proteins of viruses and bacteria used for cell attachment and invasion are candidates for degradation by proteases. trypsin from atlantic cod (gadus morhua) was previously demonstrated to have efficacy against influenza viruses in vitro and on skin. in this paper, cod trypsin is shown to be 3-12 times more effective in degrading large native proteins than its mesophilic analogue, bovine trypsin. this is in agreement with previous findings where cod trypsin was found to be the most active ...201323555095
rna-seq-based analysis of cold shock response in thermoanaerobacter tengcongensis, a bacterium harboring a single cold shock protein encoding gene.although cold shock responses and the roles of cold shock proteins in microorganisms containing multiple cold shock protein genes have been well characterized, related studies on bacteria possessing a single cold shock protein gene have not been reported. thermoanaerobacter tengcongensis mb4, a thermophile harboring only one known cold shock protein gene (ttescpc), can survive from 50° to 80 °c, but has poor natural competence under cold shock at 50 °c. we therefore examined cold shock responses ...201424667527
outer membrane vesicles from brucella abortus promote bacterial internalization by human monocytes and modulate their innate immune response.outer membrane vesicles (omvs) released by some gram-negative bacteria have been shown to exert immunomodulatory effects that favor the establishment of the infection. the aim of the present study was to assess the interaction of omvs from brucella abortus with human epithelial cells (hela) and monocytes (thp-1), and the potential immunomodulatory effects they may exert. using confocal microscopy and flow cytometry, fitc-labeled omvs were shown to be internalized by both cell types. internalizat ...201223189190
the btaf trimeric autotransporter of brucella suis is involved in attachment to various surfaces, resistance to serum and virulence.the adhesion of bacterial pathogens to host cells is an event that determines infection, and ultimately invasion and intracellular multiplication. several evidences have recently shown that this rule is also truth for the intracellular pathogen brucella. brucella suis displays the unipolar bmac and btae adhesins, which belong to the monomeric and trimeric autotransporter (ta) families, respectively. it was previously shown that these adhesins are involved in bacterial adhesion to host cells and ...201324236157
bacterial interference with canonical nfκb signalling.the human body is constantly challenged by a variety of commensal and pathogenic micro-organisms that trigger the immune system. central in the first line of defence is the pattern-recognition receptor (prr)-induced stimulation of the nfκb pathway, leading to nfκb activation. the subsequent production of pro-inflammatory cytokines and/or antimicrobial peptides results in recruitment of professional phagocytes and bacterial clearance. to overcome this, bacteria have developed mechanisms for targe ...201323873783
the rna chaperone hfq promotes fitness of actinobacillus pleuropneumoniae during porcine pleuropneumonia.actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, an economically important disease of pigs. the hfq gene in a. pleuropneumoniae, encoding the rna chaperone and posttranscriptional regulator hfq, is upregulated during infection of porcine lungs. to investigate the role of this in vivo-induced gene in a. pleuropneumoniae, an hfq mutant strain was constructed. the hfq mutant was defective in biofilm formation on abiotic surfaces. the level of pgac transcript, enc ...201323732171
matrix-assisted laser desorption ionization-time of flight mass spectrometry: a fundamental shift in the routine practice of clinical microbiology.within the past decade, clinical microbiology laboratories experienced revolutionary changes in the way in which microorganisms are identified, moving away from slow, traditional microbial identification algorithms toward rapid molecular methods and mass spectrometry (ms). historically, ms was clinically utilized as a high-complexity method adapted for protein-centered analysis of samples in chemistry and hematology laboratories. today, matrix-assisted laser desorption ionization-time of flight ...201323824373
global small rna chaperone hfq and regulatory small rnas are important virulence regulators in erwinia amylovora.hfq is a global small rna (srna) chaperone that interacts with hfq-regulated srnas and functions in the posttranscriptional regulation of gene expression. in this work, we identified hfq to be a virulence regulator in the gram-negative fire blight pathogen erwinia amylovora. deletion of hfq in e. amylovora ea1189 significantly reduced bacterial virulence in both immature pear fruits and apple shoots. analysis of virulence determinants in strain ea1189δhfq showed that hfq exerts pleiotropic regul ...201323378513
btae, an adhesin that belongs to the trimeric autotransporter family, is required for full virulence and defines a specific adhesive pole of brucella suis.brucella is responsible for brucellosis, one of the most common zoonoses worldwide that causes important economic losses in several countries. increasing evidence indicates that adhesion of brucella spp. to host cells is an important step to establish infection. we have previously shown that the bmac unipolar monomeric autotransporter mediates the binding of brucella suis to host cells through cell-associated fibronectin. our genome analysis shows that the b. suis genome encodes several addition ...201323319562
a moraxella catarrhalis two-component signal transduction system necessary for growth in liquid media affects production of two lysozyme inhibitors.there are a paucity of data concerning gene products that could contribute to the ability of moraxella catarrhalis to colonize the human nasopharynx. inactivation of a gene (mesr) encoding a predicted response regulator of a two-component signal transduction system in m. catarrhalis yielded a mutant unable to grow in liquid media. this mesr mutant also exhibited increased sensitivity to certain stressors, including polymyxin b, sds, and hydrogen peroxide. inactivation of the gene (mess) encoding ...201425312959
a moraxella catarrhalis two-component signal transduction system necessary for growth in liquid media affects production of two lysozyme inhibitors.there are a paucity of data concerning gene products that could contribute to the ability of moraxella catarrhalis to colonize the human nasopharynx. inactivation of a gene (mesr) encoding a predicted response regulator of a two-component signal transduction system in m. catarrhalis yielded a mutant unable to grow in liquid media. this mesr mutant also exhibited increased sensitivity to certain stressors, including polymyxin b, sds, and hydrogen peroxide. inactivation of the gene (mess) encoding ...201425312959
uptake of helicobacter pylori vesicles is facilitated by clathrin-dependent and clathrin-independent endocytic pathways.bacteria shed a diverse set of outer membrane vesicles that function as transport vehicles to deliver effector molecules and virulence factors to host cells. helicobacter pylori is a gastric pathogen that infects half of the world's population, and in some individuals the infection progresses into peptic ulcer disease or gastric cancer. here we report that intact vesicles from h. pylori are internalized by clathrin-dependent endocytosis and further dynamin-dependent processes, as well as in a ch ...201424846379
hepatocytes: a key cell type for innate immunity.hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. these proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide sig ...201526685902
hepatocytes: a key cell type for innate immunity.hepatocytes, the major parenchymal cells in the liver, play pivotal roles in metabolism, detoxification, and protein synthesis. hepatocytes also activate innate immunity against invading microorganisms by secreting innate immunity proteins. these proteins include bactericidal proteins that directly kill bacteria, opsonins that assist in the phagocytosis of foreign bacteria, iron-sequestering proteins that block iron uptake by bacteria, several soluble factors that regulate lipopolysaccharide sig ...201526685902
ccl20 and beta-defensin 2 production by human lung epithelial cells and macrophages in response to brucella abortus infection.both ccl20 and human β-defensin 2 (hbd2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. they are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. whereas brucella spp. can infect humans through inhalation, their ability to induce ccl20 and hbd2 in lung cells is unknown. here we show that b. abortus induces ccl20 expression in human alveolar (a549) or bronchial (calu-6) epithelial cell lines, primary alveo ...201526448160
the impact of immunosenescence on pulmonary disease.the global population is aging with significant gains in life expectancy particularly in the developed world. consequently, greater focus on understanding the processes that underlie physiological aging has occurred. key facets of advancing age include genomic instability, telomere shortening, epigenetic changes, and declines in immune function termed immunosenescence. immunosenescence and its associated chronic low grade systemic "inflamm-aging" contribute to the development and progression of ...201526199462
moonlighting o-acetylserine sulfhydrylase: new functions for an old protein.o-acetylserine sulfhydrylase a (cysk) is the pyridoxal 5'-phosphate-dependent enzyme that catalyzes the final reaction of cysteine biosynthesis in bacteria. cysk was initially identified in a complex with serine acetyltransferase (cyse), which catalyzes the penultimate reaction in the synthetic pathway. this "cysteine synthase" complex is stabilized by insertion of the cyse c-terminus into the active-site of cysk. remarkably, the cysk/cyse binding interaction is conserved in most bacterial and p ...201525731080
comparative analysis of membrane vesicles from three piscirickettsia salmonis isolates reveals differences in vesicle characteristics.membrane vesicles (mvs) are spherical particles naturally released from the membrane of gram-negative bacteria. bacterial mv production is associated with a range of phenotypes including biofilm formation, horizontal gene transfer, toxin delivery, modulation of host immune responses and virulence. this study reports comparative profiling of mvs from bacterial strains isolated from three widely disperse geographical areas. mass spectrometry identified 119, 159 and 142 proteins in mvs from three d ...201627764198
cigarette smoke alters the ability of human dendritic cells to promote anti-streptococcus pneumoniae th17 response.chronic obstructive pulmonary disease (copd) is associated with chronic inflammation and impaired immune response to pathogens leading to bacteria-induced exacerbation of the disease. a defect in th17 cytokines in response to streptococcus pneumoniae, a bacteria associated with copd exacerbations, has been recently reported. dendritic cells (dc) are professional antigen presenting cells that drive t-cells differentiation and activation. in this study, we hypothesized that exposure to cigarette s ...201627460220
the rna-binding chaperone hfq is an important global regulator of gene expression in pasteurella multocida and plays a crucial role in production of a number of virulence factors, including hyaluronic acid capsule.the gram-negative bacterium pasteurella multocida is the causative agent of a number of economically important animal diseases, including avian fowl cholera. numerous p. multocida virulence factors have been identified, including capsule, lipopolysaccharide (lps), and filamentous hemagglutinin, but little is known about how the expression of these virulence factors is regulated. hfq is an rna-binding protein that facilitates riboregulation via interaction with small noncoding rna (srna) molecule ...201626883595
kinship and diversification of bacterial penicillin-binding proteins and beta-lactamases. 19989449253
frequency of low-level bacteremia in children from birth to fifteen years of age.a single blood culture inoculated with a small volume of blood is still frequently being used for the diagnosis of bacteremia in children because of the continued belief by many that bacteria are usually found in high concentrations in the blood of pediatric patients with sepsis. to determine the importance of both blood volume cultured and the number of culture devices required for the reliable detection of pathogens in our pediatric population, blood from children from birth to 15 years of age ...200010834973
risk factors for contact lens bacterial contamination during continuous wear.microbial contamination of contact lenses is associated with corneal infection and inflammation. this study determined the microbiological, clinical, and demographic factors that are associated with bacterial contamination of a silicone hydrogel contact lens when worn for continuous wear (cw).200919786927
performances and reliability of bruker microflex lt and vitek ms maldi-tof mass spectrometry systems for the identification of clinical microorganisms.in clinical microbiology laboratories, routine microbial identification is mostly performed using culture based methodologies requiring 24 to 72 hours from culturing to identification. matrix assisted laser desorption ionization-time of flight mass spectrometry (maldi-tof ms) technology has been established as a cost effective, reliable, and faster alternative identification platform. in this study, we evaluated the reliability of the two available maldi-tof ms systems for their routine clinical ...201526793718
empirical antibiotic therapy for pneumonia in intensive care units: a multicentre, retrospective analysis of potentially pathogenic microorganisms identified by endotracheal aspirates cultures.the purpose of this investigation was to explore the presumed relationship between the days of hospitalisation and microorganisms identified by endotracheal aspirate cultures in relation to adequate empirical treatment strategies of pneumonia in the intensive care unit (icu). all potentially pathogenic microorganisms identified by (surveillance) cultures of endotracheal aspirates obtained in the icus of two dutch teaching hospitals in 2007 and 2012 were retrospectively collected and analysed. an ...201526385348
pneumonia in the neutropenic cancer patient.pneumonia is the leading cause of death among neutropenic cancer patients, particularly those with acute leukaemia. even with empiric therapy, case fatality rates of neutropenic pneumonias remain unacceptably high. however, recent advances in the management of neutropenic pneumonia offer hope for improved outcomes in the cancer setting. this review summarizes recent literature regarding the clinical presentation, microbiologic trends, diagnostic advances and therapeutic recommendations for cance ...201525784246
evaluation of the filmarray blood culture identification panel: results of a multicenter controlled trial.sepsis is a major cause of morbidity, mortality, and increased medical expense. rapid diagnosis improves outcomes and reduces costs. the filmarray blood culture identification panel (biofire diagnostics llc, salt lake city, ut), a highly multiplexed pcr assay, can identify 24 etiologic agents of sepsis (8 gram-positive, 11 gram-negative, and 5 yeast species) and three antimicrobial resistance genes (meca, vana/b, and blakpc) from positive blood culture bottles. it provides results in about 1 h w ...201626739158
in vitro activities of ertapenem (mk-0826) against clinical bacterial isolates from 11 north american medical centers.this study compared the in vitro activities of the new long-half-life carbapenem ertapenem (also known as mk-0826 and l-749,345) with those of imipenem, amoxicillin-clavulanate, and ciprofloxacin against 5,558 recent clinical isolates from 11 north american medical centers. we confirmed the greater activity of ertapenem than of imipenem against the enterobacteriaceae and the greater activity of imipenem against pseudomonads and gram-positive bacteria.200111353653
discrepancy in maldi-tof ms identification of uncommon gram-negative bacteria from lower respiratory secretions in patients with cystic fibrosis.early identification of microbial organisms from respiratory secretions of patients with cystic fibrosis (cf) is important to guide therapeutic decisions. the objective was to compare the accuracy of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (maldi-tof ms) relative to the conventional phenotypic method in identifying common bacterial isolates, including nonfermenting gram-negative bacteria, in a cohort of patients with cf.201525995646
bacteremic complications of intravascular catheter tip colonization with gram-negative micro-organisms in patients without preceding bacteremia.although gram-negative micro-organisms are frequently associated with catheter-related bloodstream infections, the prognostic value and clinical implication of a positive catheter tip culture with gram-negative micro-organisms without preceding bacteremia remains unclear. we determined the outcomes of patients with intravascular catheters colonized with these micro-organisms, without preceding positive blood cultures, and identified risk factors for the development of subsequent gram-negative ba ...201121909649
bacteremic complications of intravascular catheter tip colonization with gram-negative micro-organisms in patients without preceding bacteremia.although gram-negative micro-organisms are frequently associated with catheter-related bloodstream infections, the prognostic value and clinical implication of a positive catheter tip culture with gram-negative micro-organisms without preceding bacteremia remains unclear. we determined the outcomes of patients with intravascular catheters colonized with these micro-organisms, without preceding positive blood cultures, and identified risk factors for the development of subsequent gram-negative ba ...201121909649
infectious etiologies of acute febrile illness among patients seeking health care in south-central cambodia.the agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. from december 2006 to december 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central cambodia were enrolled in a study to elucidate the etiologies. upon enrollment, respiratory specimens, whole blood, and serum were collected. testing was performed ...201222302857
real-time pcr taqman assay for rapid screening of bloodstream infection.sepsis is one of the main causes of mortality and morbidity. the rapid detection of pathogens in blood of septic patients is essential for adequate antimicrobial therapy and better prognosis. this study aimed to accelerate the detection and discrimination of gram-positive (gp) and gram-negative (gn) bacteria and candida species in blood culture samples by molecular methods.201424393579
pathogens protection against the action of disinfectants in multispecies biofilms.biofilms constitute the prevalent way of life for microorganisms in both natural and man-made environments. biofilm-dwelling cells display greater tolerance to antimicrobial agents than those that are free-living, and the mechanisms by which this occurs have been investigated extensively using single-strain axenic models. however, there is growing evidence that interspecies interactions may profoundly alter the response of the community to such toxic exposure. in this paper, we propose an overvi ...201526236291
evaluation of various culture media for detection of rapidly growing mycobacteria from patients with cystic fibrosis.isolation of nontuberculous mycobacteria (ntm) from the sputum of patients with cystic fibrosis (cf) is challenging due to overgrowth by rapidly growing species that colonize the lungs of patients with cf. extended incubation on burkholderia cepacia selective agar (bcsa) has been recommended as an expedient culture method for the isolation of rapidly growing ntm in this setting. the aim of this study was to assess five selective media designed for the isolation of burkholderia cepacia complex, a ...201627098962
rapid identification of bacteria from positive blood cultures by fluorescence-based pcr-single-strand conformation polymorphism analysis of the 16s rrna gene.bacteremia continues to result in significant morbidity and mortality, particularly in patients who are immunocompromised. currently, patients with suspected bacteremia are empirically administered broad-spectrum antibiotics, as definitive diagnosis relies upon the use of blood cultures, which impose significant delays in and limitations to pathogen identification. to address the limitations of growth-based identification, the sequence variability of the 16s rrna gene of bacteria was targeted fo ...200010655337
in vitro activity of tp-271 against mycobacterium abscessus, mycobacterium fortuitum, and nocardia species.the in vitro activities of tp-271, a novel fluorocycline antimicrobial, against 22 isolates of mycobacterium abscessus, 22 isolates of mycobacterium fortuitum, and 19 isolates of nocardia spp. were studied by a microtiter broth dilution method. the mic(90)s for m. abscessus, m. fortuitum, and nocardia spp. were 0.5 μg/ml, 0.03 μg/ml, and 8 μg/ml, respectively. tp-271 was significantly more active than the respective control drug in virtually all tests.201222585214
tricyclic gyrb/pare (tribe) inhibitors: a new class of broad-spectrum dual-targeting antibacterial agents.increasing resistance to every major class of antibiotics and a dearth of novel classes of antibacterial agents in development pipelines has created a dwindling reservoir of treatment options for serious bacterial infections. the bacterial type iia topoisomerases, dna gyrase and topoisomerase iv, are validated antibacterial drug targets with multiple prospective drug binding sites, including the catalytic site targeted by the fluoroquinolone antibiotics. however, growing resistance to fluoroquin ...201324386374
rational design of broad spectrum antibacterial activity based on a clinically relevant enoyl-acyl carrier protein (acp) reductase inhibitor.determining the molecular basis for target selectivity is of particular importance in drug discovery. the ideal antibiotic should be active against a broad spectrum of pathogenic organisms with a minimal effect on human targets. cg400549, a staphylococcus-specific 2-pyridone compound that inhibits the enoyl-acyl carrier protein reductase (fabi), has recently been shown to possess human efficacy for the treatment of methicillin-resistant staphylococcus aureus infections, which constitute a seriou ...201424739388
gsk3β and the control of infectious bacterial diseases.glycogen synthase kinase 3β (gsk3β) has been shown to be a crucial mediator of the intensity and direction of the innate immune system response to bacterial stimuli. this review focuses on: (i) the central role of gsk3β in the regulation of pathogen-induced inflammatory responses through the regulation of pro- and anti-inflammatory cytokine production, (ii) the extensive ongoing efforts to exploit gsk3β for its therapeutic potential in the control of infectious diseases, and (iii) the increasing ...201424618402
time for a change: addressing r&d and commercialization challenges for antibacterials.the antibacterial therapeutic area has been described as the perfect storm. resistance is increasing to the point that our hospitals encounter patients infected with untreatable pathogens, the overall industry pipeline is described as dry and most multinational pharmaceutical companies have withdrawn from the area. major contributing factors to the declining antibacterial industry pipeline include scientific challenges, clinical/regulatory hurdles and low return on investment. this paper examine ...201525918443
association of targeted multiplex pcr with resequencing microarray for the detection of multiple respiratory pathogens.a large number of viral and bacterial organisms are responsible for community-acquired pneumonia (cap) which contributes to substantial burden on health management. a new resequencing microarray (rpm-ivdc1) associated with targeted multiplex pcr was recently developed and validated for multiple respiratory viruses detection and discrimination. in this study, we evaluated the capability of rpm-ivdc1 for simultaneous identification of multiple viral and bacterial organisms. the nasopharyngeal aspi ...201526074910
identification of aeromonas hydrophila genes preferentially expressed after phagocytosis by tetrahymena and involvement of methionine sulfoxide reductases.free-living protozoa affect the survival and virulence evolution of pathogens in the environment. in this study, we explored the fate of aeromonas hydrophila when co-cultured with the bacteriovorous ciliate tetrahymena thermophila and investigated bacterial gene expression associated with the co-culture. virulent a. hydrophila strains were found to have ability to evade digestion in the vacuoles of this protozoan. in a. hydrophila, a total of 116 genes were identified as up-regulated following c ...201628083518
fmvb: a francisella tularensis magnesium-responsive outer membrane protein that plays a role in virulence.francisella tularensis is the causative agent of the lethal disease tularemia. despite decades of research, little is understood about why f. tularensis is so virulent. bacterial outer membrane proteins (omps) are involved in various virulence processes, including protein secretion, host cell attachment, and intracellular survival. many pathogenic bacteria require metals for intracellular survival and omps often play important roles in metal uptake. previous studies identified three f. tularensi ...201627513341
identification and characterization of msf, a novel virulence factor in haemophilus influenzae.haemophilus influenzae is an opportunistic pathogen. the emergence of virulent, non-typeable strains (nthi) emphasizes the importance of developing new interventional targets. we screened the nthi supragenome for genes encoding surface-exposed proteins suggestive of immune evasion, identifying a large family containing sel1-like repeats (slrs). clustering identified ten slr-containing gene subfamilies, each with various numbers of slrs per gene. individual strains also had varying numbers of slr ...201626977929
pleiotropic role of the rna chaperone protein hfq in the human pathogen clostridium difficile.clostridium difficile is an emergent human pathogen and the most common cause of nosocomial diarrhea. our recent data strongly suggest the importance of rna-based mechanisms for the control of gene expression in c. difficile. in an effort to understand the function of the rna chaperone protein hfq, we constructed and characterized an hfq-depleted strain in c. difficile. hfq depletion led to a growth defect, morphological changes, an increased sensitivity to stresses, and a better ability to spor ...201424982306
nitrous oxide production and consumption: regulation of gene expression by gas-sensitive transcription factors.several biochemical mechanisms contribute to the biological generation of nitrous oxide (n(2)o). n(2)o generating enzymes include the respiratory nitric oxide (no) reductase, an enzyme from the flavo-diiron family, and flavohaemoglobin. on the other hand, there is only one enzyme that is known to use n(2)o as a substrate, which is the respiratory n(2)o reductase typically found in bacteria capable of denitrification (the respiratory reduction of nitrate and nitrite to dinitrogen). this article w ...201222451107
ralstonia solanacearum uses inorganic nitrogen metabolism for virulence, atp production, and detoxification in the oxygen-limited host xylem environment.genomic data predict that, in addition to oxygen, the bacterial plant pathogen ralstonia solanacearum can use nitrate (no3(-)), nitrite (no2(-)), nitric oxide (no), and nitrous oxide (n2o) as terminal electron acceptors (teas). genes encoding inorganic nitrogen reduction were highly expressed during tomato bacterial wilt disease, when the pathogen grows in xylem vessels. direct measurements found that tomato xylem fluid was low in oxygen, especially in plants infected by r. solanacearum. xylem f ...201525784703
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