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oxyr-activated expression of dps is important for vibrio cholerae oxidative stress resistance and pathogenesis.vibrio cholerae is the causative agent of cholera, a dehydrating diarrheal disease. this gram-negative pathogen is able to modulate its gene expression in order to combat stresses encountered in both aquatic and host environments, including stress posed by reactive oxygen species (ros). in order to further the understanding of v. cholerae's transcriptional response to ros, we performed an rna sequencing analysis to determine the transcriptional profile of v. cholerae when exposed to hydrogen hyd ...201728151956
a cocktail of three virulent bacteriophages prevents vibrio cholerae infection in animal models.effective prevention strategies will be essential in reducing disease burden due to bacterial infections. here we harness the specificity and rapid-acting properties of bacteriophages as a potential prophylaxis therapy for cholera, a severely dehydrating disease caused by vibrio cholerae. to this end, we test a cocktail of three virulent phages in two animal models of cholera pathogenesis (infant mouse and rabbit models). oral administration of the phages up to 24 h before v. cholerae challenge ...201728146150
oxyr2 modulates oxyr1 activity and vibrio cholerae oxidative stress response.bacteria have developed capacities to deal with different stresses and adapt to different environmental niches. the human pathogen vibrio cholerae, the causative agent of the severe diarrheal disease cholera, utilizes the transcriptional regulator oxyr to activate genes related to oxidative stress resistance, including peroxiredoxin prxa, in response to hydrogen peroxide. in this study, we identified another oxyr homolog in v. cholerae, which we named oxyr2, and we renamed the previous oxyr oxyr ...201728138024
tracking disease: digital epidemiology offers new promise in predicting outbreaks.on 19 october 2010, ten months after a devastating earthquake hit haiti, the haitian ministry of public health and population (mspp) was notified of a sudden surge in patients suffering from watery diarrhea and dehydration. two days later, the haiti national public health laboratory identified the culprit: vibrio cholerae. on 22 october, officials announced the first cholera outbreak in haiti in more than a century.201728129137
biochemical basis for activation of virulence genes by bile salts in vibrio parahaemolyticus.bile salts act as a stressor to bacteria that transit the intestinal tract. enteric pathogens have hijacked bile as an intestinal signal to regulate virulence factors. we recently demonstrated that vibrio parahemolyticus senses bile salts via a heterodimeric receptor formed by the periplasmic domains of inner-membrane proteins vtra and vtrc. crystal structures of the periplasmic complex reveal that vtra and vtrc form a β-barrel that binds bile salts in its hydrophobic interior to activate the vt ...201728129014
biological properties and chemical composition of jatropha neopauciflora pax.ethnopharmacological relevance. jatropha neopauciflora (pax) is an endemic species of the tehuacan- cuicatlan valley, mexico. this species has long been used as a remedy to alleviate illnesses of bacterial, fungal and viral origin. aim of the study. experimentally test the traditional use of jatropha neopauciflora in mexican traditional medicine.201728331913
season-specific occurrence of potentially pathogenic vibrio spp. on the southern coast of south korea.vibrio species are widely distributed in warm estuarine and coastal environments, and they can infect humans through the consumption of raw and mishandled contaminated seafood. in this study, we aimed to isolate and observe the distribution of enteropathogenic vibrio spp. from environments of the southern coast of south korea over a season cycle. a total of 10,983 isolates of vibrio spp. were obtained from tidal water and mud samples over a 1-year period from five sampling sites along the southw ...201727836844
3-amino 1,8-naphthalimide, a structural analog of the anti-cholera drug virstatin inhibits chemically-biased swimming and swarming motility in vibrios.a screen for inhibitors of vibrio cholerae motility identified the compound 3-amino 1,8-naphthalimide (3-a18ni), a structural analog of the cholera drug virstatin. similar to virstatin, 3-a18ni diminished cholera toxin production. in contrast, 3-a18ni impeded swimming and/or swarming motility of v. cholerae and v. parahemolyticus suggesting that it could target the chemotaxis pathway shared by the polar and lateral flagellar system of vibrios. 3-a18ni did not inhibit the expression of v. cholera ...201728392408
chemotactic behaviors of vibrio cholerae cells.vibrio cholerae, the causative agent of cholera, swims in aqueous environments with a single polar flagellum. in a spatial gradient of a chemical, the bacterium can migrate in "favorable" directions, a property that is termed chemotaxis. the chemotaxis of v. cholerae is not only critical for survival in various environments and but also is implicated in pathogenicity. in this chapter, we describe how to characterize the chemotactic behaviors of v. cholerae: these methods include swarm assay, tem ...201728389961
an electrochemical strategy using multifunctional nanoconjugates for efficient simultaneous detection of escherichia coli o157: h7 and vibrio cholerae o1.the rapid and accurate quantification of the pathogenic bacteria is extremely critical to decrease the bacterial infections in all areas related to health and safety. we have developed an electrochemical strategy for simultaneous ultrasensitive detection of e. coli o157:h7 and vibrio cholerae o1. this approach was based on the specific immune recognition of different pathogenic bacteria by multifunctional nanoconjugates and subsequent signal amplification. by employing the proposed biosensor, th ...201728382165
iron chelators inhibit the heme-degradation reaction by hutz from vibrio cholerae.hutz is a heme-degrading enzyme. we found that the heme-degradation reaction by hutz is inhibited by the iron chelators. kinetic analysis of each heme-degradation step suggests that water molecules hydrogen bonded to thr27 are involved in proton transfer to fe(iii)-oo(-), and that this step is inhibited by iron chelators.201728352909
non-o1/non-o139 vibrio cholerae septicaemia in a saudi man: a case report.background. the non-o1/non-o139 serogroups of vibrio cholerae occur in diverse natural niches, and usually cause mild and self-limiting gastrointestinal illness. however, they have well-documented potential to cause invasive and extra-intestinal infections among immunocompromised patients. furthermore, their ability to grow in low-salinity surface water, and the existence of asymptomatic human carriers, suggest novel acquisition routes for this unusual infection, even in people without obvious r ...201728348803
vibrio cholerae vcib mediates iron reduction.vibrio cholerae is the causative agent of the severe diarrheal disease cholera. v. cholerae thrives within the human host where it replicates to high numbers but also persists within the aquatic environments of ocean and brackish water. to survive within these nutritionally diverse environments, v. cholerae must encode the necessary tools to acquire the essential nutrient iron in all forms it may encounter. a prior study of systems involved in iron transport in v. cholerae revealed the existence ...201728348025
environmental fluctuation governs selection for plasticity in biofilm production.bacteria can grow in a free-swimming state, as planktonic cells, or in surface-attached communities, termed biofilms. the planktonic and biofilm growth modes differ dramatically with respect to spatial constraints, nutrient access, population density and cell-cell interactions. fitness trade-offs underlie how successfully bacteria compete in each of these environments. accordingly, some bacteria have evolved to be specialists in biofilm formation, while others specialize in planktonic growth. th ...201728338673
chloroform-free permeabilization for improved detection of β-galactosidase activity in vibrio cholerae.lacz (β-galactosidase) is used to monitor the transcription of genes in reporter strains carrying the lacz gene under the control of a promotor of interest. this protocol for lacz activity determinations in vibrio cholerae following detergent lysis results in 2.5-fold increase of lacz activities compared to lysis with chloroform.201728336461
a new class of inhibitors of the arac family virulence regulator vibrio cholerae toxt.vibrio cholerae is responsible for the diarrheal disease cholera that infects millions of people worldwide. while vaccines protecting against cholera exist, and oral rehydration therapy is an effective treatment method, the disease will remain a global health threat until long-term solutions such as improved sanitation and access to clean water become widely available. because of this, there is a pressing need for potent therapeutics that can either mitigate cholera symptoms, or act prophylactic ...201728332578
sequential displacement of type vi secretion system effector genes leads to evolution of diverse immunity gene arrays in vibrio cholerae.type vi secretion systems (t6ss) enable bacteria to engage neighboring cells in contact-dependent competition. in vibrio cholerae, three chromosomal clusters each encode a pair of effector and immunity genes downstream of those encoding the t6ss structural machinery for effector delivery. different combinations of effector-immunity proteins lead to competition between strains of v. cholerae, which are thought to be protected only from the toxicity of their own effectors. screening of all publica ...201728327641
occurrence and virulence properties of vibrio and salinivibrio isolates from tropical lagoons of the southern caribbean sea.the vibrionaceae are gram-negative bacteria present in marine and estuarine environments worldwide, including several species known as important pathogens to humans and aquatic organisms. the aim of this research was to investigate the occurrence and virulence properties of vibrio and salinivibrio isolated from lagoons at cuare wildlife refuge and margarita island in the southern caribbean sea. water, plankton and oyster samples were collected during october 2011 and march 2012 and examined by s ...201728324231
a vibrio cholerae autoinducer-receptor pair that controls biofilm formation.quorum sensing (qs) is a cell-cell communication process that enables bacteria to track cell population density and orchestrate collective behaviors. qs relies on the production and detection of, and the response to, extracellular signal molecules called autoinducers. in vibrio cholerae, multiple qs circuits control pathogenesis and biofilm formation. here, we identify and characterize a new qs autoinducer-receptor pair. the autoinducer is 3,5-dimethylpyrazin-2-ol (dpo). dpo is made from threoni ...201728319101
synthesis and human/bacterial carbonic anhydrase inhibition with a series of sulfonamides incorporating phthalimido moieties.a series of sulfonamides was obtained by reacting substituted-2-(1,3-dioxo-1,3-dihydroisobenzofuran-5-carboxamido)benzoic acids with aromatic sulfonamides incorporating primary amino moieties. the new compounds were investigated as inhibitor of four carbonic anhydrase (ca, ec 4.2.1.1) isoforms, the human (h) hca i and ii, and the α- and β-class cas from the pathogenic bacterium vibrio cholerae, vchcaα and vhccaβ. hca i was effectively inhibited by the new sulfonamides, with inhibition constants ...201728318894
cholera.cholera is an acute, watery diarrhoeal disease caused by vibrio cholerae of the o1 or o139 serogroups. in the past two centuries, cholera has emerged and spread from the ganges delta six times and from indonesia once to cause global pandemics. rational approaches to the case management of cholera with oral and intravenous rehydration therapy have reduced the case fatality of cholera from more than 50% to much less than 1%. despite improvements in water quality, sanitation, and hygiene, as well a ...201728302312
late assembly of the vibrio cholerae cell division machinery postpones septation to the last 10% of the cell cycle.bacterial cell division is a highly regulated process, which involves the formation of a complex apparatus, the divisome, by over a dozen proteins. in the few model bacteria in which the division process was detailed, divisome assembly occurs in two distinct steps: a few proteins, including the ftsz tubulin-like protein, form a membrane associated contractile ring, the z-ring, at ~30% of the cell cycle. the z-ring serves as a scaffold for the recruitment of a second series of proteins, including ...201728300142
identification of the binding sites for ubiquinone and inhibitors in the na(+)-pumping nadh-ubiquinone oxidoreductase of vibrio cholerae by photoaffinity labeling.the na(+)-pumping nadh-quinone oxidoreductase (na(+)-nqr) is the first enzyme of the respiratory chain and the main ion transporter in many marine and pathogenic bacteria, including vibrio cholerae the v. cholerae na(+)-nqr has been extensively studied, but its binding sites for ubiquinone and inhibitors remain controversial. here, using a photoreactive ubiquinone puq-3 as well as two aurachin-type inhibitors [(125)i]pad-1 and [(125)i]pad-2 and photoaffinity labeling experiments on the isolated ...201728298441
fish as hosts of vibrio cholerae.vibrio cholerae, the causative agent of pandemic cholera, is abundant in marine and freshwater environments. copepods and chironomids are natural reservoirs of this species. however, the ways v. cholerae is globally disseminated are as yet unknown. here we review the scientific literature that provides evidence for the possibility that some fish species may be reservoirs and vectors of v. cholerae. so far, v. cholerae has been isolated from 30 fish species (22 freshwater; 9 marine). v. cholerae ...201728293221
an amoebal grazer of cyanobacteria requires cobalamin produced by heterotrophic bacteria.amoebae are unicellular eukaryotes that consume microbial prey through phagocytosis, playing a role in shaping microbial foodwebs. many amoebal species can be cultivated axenically in rich media or monoxenically with single bacterial prey species. here we characterize heterolobosean amoeba lpg3, a recent natural isolate, which is unable to grow on unicellular cyanobacteria, its primary food source, in the absence of a heterotrophic bacterium, a pseudomonas species coisolate. to investigate the m ...201728283521
vibrio cholerae lipopolysaccharide loaded chitosan nanoparticle could save life by induction of specific immunoglobulin isotype.the lipopolysaccharide (lps) of vibrio cholerae (v. cholerae) plays an important role in cholera disease and the induction of primary protection. in this study, we evaluate mice humoral immune response in intranasal and intraperitoneal administrated v. cholerae lps. the results showed that the intranasal administration of lps-chitosan nanoparticle induced the high level of antibodies compared to intraperitoneal injection of antigen without chitosan (p < .001). these results indicated that intran ...201728278575
vibrio cholerae o1 with reduced susceptibility to ciprofloxacin and azithromycin isolated from a rural coastal area of bangladesh.cholera outbreaks occur each year in the remote coastal areas of bangladesh and epidemiological surveillance and routine monitoring of cholera in these areas is challenging. in this study, a total of 97 vibrio cholerae o1 isolates from mathbaria, bangladesh, collected during 2010 and 2014 were analyzed for phenotypic and genotypic traits, including antimicrobial susceptibility. of the 97 isolates, 95 possessed ctx-phage mediated genes, ctxa, ace, and zot, and two lacked the cholera toxin gene, c ...201728270803
pandemics, pathogenicity and changing molecular epidemiology of cholera in the era of global warming.vibrio cholerae, a gram-negative, non-spore forming curved rod is found in diverse aquatic ecosystems around the planet. it is classified according to its major surface antigen into around 206 serogroups, of which o1 and o139 cause epidemic cholera. a recent spatial modelling technique estimated that around 2.86 million cholera cases occur globally every year, and of them approximately 95,000 die. about 1.3 billion people are currently at risk of infection from cholera. meta-analysis and mathema ...201728270154
the proximity of ribosomal protein genes to oric enhances vibrio cholerae fitness in the absence of multifork replication.recent works suggest that bacterial gene order links chromosome structure to cell homeostasis. comparative genomics showed that, in fast-growing bacteria, ribosomal protein genes (rp) locate near the replication origin (oric). we recently showed that vibrio cholerae employs this positional bias as a growth optimization strategy: under fast-growth conditions, multifork replication increases rp dosage and expression. however, rp location may provide advantages in a dosage-independent manner: for e ...201728246358
transcriptional and post-transcriptional regulation of pst2 operon expression in vibrio cholerae o1.one of the most abundant proteins in v. cholerae o1 cells grown under inorganic phosphate (pi) limitation is psts, the periplasmic pi-binding component of the high-affinity pi transport system pst2 (pstscab), encoded in pst2 operon (psts-pstc2-psta2-pstb2). besides its role in pi uptake, pst2 has been also associated with v. cholerae virulence. however, the mechanisms regulating pst2 expression and the non-stoichiometric production of the pst2 components under pi-limitation are unknown. a comput ...201728242357
differential regulation of riboflavin supply genes in vibrio cholerae.riboflavin is the precursor of important redox cofactors such as flavin mononucleotide (fmn) and flavin adenine dinucleotide, required for several biological processes. vibrio cholerae, a pathogenic bacterium responsible for the cholera disease, possesses the ability to biosynthesize de novo as well as to uptake riboflavin through the riboflavin biosynthetic pathway (rbp) and the ribn importer, respectively. the intra-organism relationship between riboflavin biosynthesis and uptake functions has ...201728239422
structural and biochemical studies on vibrio cholerae hsp31 reveals a novel dimeric form and glutathione-independent glyoxalase activity.vibrio cholerae experiences a highly hostile environment at human intestine which triggers the induction of various heat shock genes. the hcha gene product of v. cholerae o395, referred to a hypothetical intracellular protease/amidase vchsp31, is one such stress-inducible homodimeric protein. our current study demonstrates that vchsp31 is endowed with molecular chaperone, amidopeptidase and robust methylglyoxalase activities. through site directed mutagenesis coupled with biochemical assays on v ...201728235098
whole-genome sequencing of vibrio cholerae o1 el tor strains isolated in ukraine (2011) and russia (2014).here, we present the draft whole-genome sequence of vibrio cholerae o1 el tor strains 76 and m3265/80, isolated in mariupol, ukraine, and moscow, russia. the presence of various mutations detected in virulence-associated mobile elements indicates high genetic similarity of the strains reported here with new highly virulent variants of the cholera agent v. cholerae.201728232438
genetic characterization of vibrio cholerae o1 isolates from outbreaks between 2011 and 2015 in tanzania.cholera outbreaks have occurred in tanzania since 1974. to date, the genetic epidemiology of these outbreaks has not been assessed.201728219321
structure and function of vibrio cholerae accessory cholera enterotoxin in presence of gold nanoparticles: dependence on morphology.accessory cholera enterotoxin (ace) is a classical enterotoxin produced by vibrio cholerae, the causative agent for cholera. considering the crucial role of ace in pathogenesis of cholera, we explored the modulation of structure/function of ace using gold nanoparticles (aunps) of different size and shape - spherical (auns10 and auns100, the number indicating the diameter in nm) and rod (aunr10).201728215703
circulation of a quorum-sensing-impaired variant of vibrio cholerae strain c6706 masks important phenotypes.vibrio cholerae, the causative agent of cholera, is a model organism for studying virulence regulation, biofilm formation, horizontal gene transfer, and the cell-to-cell communication known as quorum sensing (qs). as in any research field, discrepancies between data from diverse laboratories are sometimes observed for v. cholerae. such discrepancies are often caused by the use of diverse patient or environmental isolates. in this study, we investigated the inability of a few laboratories to repr ...201727303743
molecular dynamics of sialic acid analogues complex with cholera toxin and dft optimization of ethylene glycol-mediated zinc nanocluster conjugation.cholera is an infectious disease caused by cholera toxin (ct) protein of bacterium vibrio cholerae. a sequence of sialic acid (n-acetylneuraminic acid, neunac or neu5ac) analogues modified in its c-5 position is modelled using molecular modelling techniques and docked against the ct followed by molecular dynamics simulations. docking results suggest better binding affinity of neunac analogue towards the binding site of ct. the neunac analogues interact with the active site residues glu:11, tyr:1 ...201726733187
disease dynamics in a coupled cholera model linking within-host and between-host interactions.a new modelling framework is proposed to study the within-host and between-host dynamics of cholera, a severe intestinal infection caused by the bacterium vibrio cholerae. the within-host dynamics are characterized by the growth of highly infectious vibrios inside the human body. these vibrios shed from humans contribute to the environmental bacterial growth and the transmission of the disease among humans, providing a link from the within-host dynamics at the individual level to the between-hos ...201727646159
strong ph dependence of coupling efficiency of the na+ - translocating nadh:quinone oxidoreductase (na+-nqr) of vibrio cholerae.the na+-translocating nadh:quinone oxidoreductase (nqr) is the entry site for electrons into the respiratory chain of vibrio cholerae, the causative agent of cholera disease. nqr couples the electron transfer from nadh to ubiquinone to the translocation of sodium ions across the membrane. we investigated the ph dependence of electron transfer and generation of a transmembrane voltage (δψ) by nqr reconstituted in liposomes with na+ or li+ as coupling cation. δψ formation was followed with the vol ...201727639271
achievements and challenges for the use of killed oral cholera vaccines in the global stockpile era.cholera remains an important but neglected public health threat, affecting the health of the poorest populations and imposing substantial costs on public health systems. cholera can be eliminated where access to clean water, sanitation, and satisfactory hygiene practices are sustained, but major improvements in infrastructure continue to be a distant goal. new developments and trends of cholera disease burden, the creation of affordable oral cholera vaccines (ocvs) for use in developing countrie ...201727813703
h-ns: an overarching regulator of the vibrio cholerae life cycle.vibrio cholerae has become a model organism for studies connecting virulence, pathogen evolution and infectious disease ecology. the coordinate expression of motility, virulence and biofilm enhances its pathogenicity, environmental fitness and fecal-oral transmission. the histone-like nucleoid structuring protein negatively regulates gene expression at multiple phases of the v. cholerae life cycle. here we discuss: (i) the regulatory and structural implications of h-ns chromatin-binding in the t ...201727492955
antibacterial and antispasmodic activities of a dichloromethane fraction of an ethanol extract of stem bark of piliostigma reticulatum.this study presents the antispasmodic and antibacterial properties of an ethanol extract and fractions the of stem bark of piliostigma reticulatum.201725883517
xer site specific recombination: double and single recombinase systems.the separation and segregation of newly replicated bacterial chromosomes can be constrained by the formation of circular chromosome dimers caused by crossing over during homologous recombination events. in escherichia coli and most bacteria, dimers are resolved to monomers by site-specific recombination, a process performed by two chromosomally encoded tyrosine recombinases (xerc and xerd). xercd recombinases act at a 28 bp recombination site dif, which is located at the replication terminus reg ...201728373867
fast growth conditions uncouple the final stages of chromosome segregation and cell division in escherichia coli.homologous recombination between the circular chromosomes of bacteria can generate chromosome dimers. they are resolved by a recombination event at a specific site in the replication terminus of chromosomes, dif, by dedicated tyrosine recombinases. the reaction is under the control of a cell division protein, ftsk, which assembles into active dna pumps at mid-cell during septum formation. previous studies suggested that activation of xer recombination at dif was restricted to chromosome dimers i ...201728358835
ribosome-dependent vibrio cholerae mrnase higb2 is regulated by a β-strand sliding mechanism.toxin-antitoxin (ta) modules are small operons involved in bacterial stress response and persistence. higba operons form a family of ta modules with an inverted gene organization and a toxin belonging to the rele/pare superfamily. here, we present the crystal structures of chromosomally encoded vibrio cholerae antitoxin (vchiga2), toxin (vchigb2) and their complex, which show significant differences in structure and mechanisms of function compared to the higba module from plasmid rts1, the defin ...201728334932
induction of immunomodulatory mir-146a and mir-155 in small intestinal epithelium of vibrio cholerae infected patients at acute stage of cholera.the potential immunomodulatory role of micrornas in small intestine of patients with acute watery diarrhea caused by vibrio cholerae o1 or enterotoxigenic escherichia coli (etec) infection was investigated. duodenal biopsies were obtained from study-participants at the acute (day 2) and convalescent (day 21) stages of disease, and from healthy individuals. levels of mir-146a, mir-155 and mir-375 and target gene (irak1, traf6, card10) and 11 cytokine mrnas were determined by qrt-pcr. the cellular ...201728319200
stringent factor and proteolysis control of sigma factor rpos expression in vibrio cholerae.vibrio cholerae can colonize the gastrointestinal track of humans and cause the disease cholera. during colonization, the alternative sigma factor, rpos, controls a process known as "mucosal escape response," defining a specific spatial and temporal response and effecting chemotaxis and motility. in this report, the expression and proteolytic control of rpos in v. cholerae was characterized. to date, aspects of proteolysis control, the involved components, and proteolysis regulation have not bee ...201728228329
structure and dynamics of type iii periplasmic proteins vcfhud and vchutb reveal molecular basis of their distinctive ligand binding properties.molecular mechanisms of xenosiderophore and heme acquisitions using periplasmic binding protein (pbp) dependent atp-binding cassette transporters to scavenge the essential nutrient iron are elusive yet in vibrio cholerae. our current study delineates the structures, dynamics and ligand binding properties of two type iii pbps of v. cholerae, vcfhud and vchutb. through crystal structures and fluorescence quenching studies we demonstrate unique features of vcfhud to bind both hydroxamate and catech ...201728216648
surface expression of helicobacter pylori hpaa adhesion antigen on vibrio cholerae, enhanced by co-expressed enterotoxigenic escherichia coli fimbrial antigens.helicobacter pylori infection can cause peptic ulceration and is associated with gastric adenocarcinoma. this study aimed to construct and characterize a non-virulent vibrio cholerae o1 strain, which grows more rapidly than h. pylori, as vector for h. pylori antigens for possible use as a vaccine strain against h. pylori. this was done by recombinant expression of the h. pylori adhesion antigen hpaa alone or, as a proof of principle, together with different colonization factor (cf) antigens of e ...201728215587
attachment of 13 types of foodborne bacteria to jalapeño and serrano peppers and antibacterial effect of roselle calyx extracts, sodium hypochlorite, colloidal silver, and acetic acid against these foodborne bacteria on peppers.chili peppers are a very important crop in mexico. however, these peppers have been associated with salmonella infection outbreaks in the united states, and salmonella and diarrheagenic escherichia coli pathotypes have been isolated from jalapeño and serrano peppers in mexico. to decrease microbial contamination of fruits and vegetables, chemical agents are commonly used; however, chemical agents used to eliminate pathogenic bacteria on vegetables have a limited antimicrobial effect. roselle ( h ...201728199144
identification and antimicrobial resistance patterns of bacterial enteropathogens from children aged 0-59 months at the university teaching hospital, lusaka, zambia: a prospective cross sectional study.bacterial diarrhoeal disease is among the most common causes of mortality and morbidity in children 0-59 months at the university teaching hospital in lusaka, zambia. however, most cases are treated empirically without the knowledge of aetiological agents or antimicrobial susceptibility patterns. the aim of this study was, therefore, to identify bacterial causes of diarrhoea and determine their antimicrobial susceptibility patterns in stool specimens obtained from the children at the hospital.201728152988
cross feeding of glucose metabolism byproducts of escherichia coli human gut isolates and probiotic strains affect survival of vibrio cholerae.vibrio cholerae converts glucose into either acid or the neutral end product acetoin and its survival in carbohydrate enriched media is linked to the nature of the byproducts produced. it has been demonstrated in this study that escherichia coli strain isolated from the gut of healthy human volunteers and the commonly used probiotic e. coli nissle strain that metabolize glucose to acidic byproducts drastically reduce the survival of v. cholerae strains irrespective of their glucose sensitivity a ...201728105081
structural insights into the secretin translocation channel in the type ii secretion system.the secretin gspd of the type ii secretion system (t2ss) forms a channel across the outer membrane in gram-negative bacteria to transport substrates from the periplasm to the extracellular milieu. the lack of an atomic-resolution structure of the gspd channel hinders the investigation of substrate translocation mechanism of t2ss. here we report cryo-em structures of two gspd channels (∼1 mda), from escherichia coli k12 and vibrio cholerae, at ∼3 å resolution. the structures reveal a pentadecamer ...201728067918
targeting and alteration of tight junctions by bacteria and their virulence factors such as clostridium perfringens enterotoxin.the integrity of tight junctions, which regulate paracellular permeability, is challenged by many bacterial pathogens. this is caused by inflammatory responses triggered by pathogens and direct interaction of bacteria or their toxins with host epithelial cells. in some cases, tight junction proteins represent receptors for cell surface proteins or toxins of the pathogen, such as clostridium perfringens enterotoxin (cpe). cpe causes diarrhea and cramps-the symptoms of a common foodborne illness, ...201727864644
in vitro antibacterial activity of aqueous and ethanol extracts of aristolochia indica and toddalia asiatica against multidrug-resistant bacteria.bacteria have developed multidrug resistance against available antimicrobial agents. infectious diseases caused by these multidrug-resistant bacteria are major causes of morbidity and mortality in human beings. synthetic drugs are expensive and inadequate for the treatment of diseases, causing side effects and ineffective against multidrug-resistant bacteria. the medicinal plants are promising to have effective antimicrobial property due to presence of phytochemical compounds like alkaloids, fla ...201726997710
ctxϕ: exploring new alternatives in host factor-mediated filamentous phage replications.for a long time ff phages from escherichia coli provided the majority of the knowledge about the rolling circle replication mechanism of filamentous phages. host factors involved in coliphages replication have been fully identified. based on these studies, the function of rep protein as the accessory helicase directly implicated in filamentous phage replication was considered a paradigm. we recently reported that the replication of some filamentous phages from vibrio cholerae, including the chol ...201727607139
immunochromatographic detection of the heat-labile enterotoxin of enterotoxigenic escherichia coli with cross-detection of cholera toxin.here, we report the development of an immunochromatographic test strip that can detect heat-labile enterotoxin (lt) produced by enterotoxigenic escherichia coli. five types of monoclonal antibody (mab)-producing hybridomas were isolated: three mabs were a subunit specific and two were b subunit specific. four mabs also cross-reacted with both lt proteins derived from swine and human e. coli strains, but only one mab 57b9 additionally cross-reacted with cholera toxin. thus, mab 57b9 was used to f ...201727940044
random versus cell cycle-regulated replication initiation in bacteria: insights from studying vibrio cholerae chromosome 2.bacterial chromosomes initiate replication at a fixed time in the cell cycle, whereas there is generally no particular time for plasmid replication initiation or chromosomal replication initiation from integrated plasmids. in bacteria with divided genomes, the replication system of one of the chromosomes typically resembles that of bacteria with undivided genomes, whereas the remaining chromosomes have plasmid-like replication systems. for example, in vibrio cholerae, a bacterium with two chromo ...201727903655
complex secondary metabolites from ludwigia leptocarpa with potent antibacterial and antioxidant activities.diarrhea continues to be one of the most common causes of morbidity and mortality among infants and children in developing countries. the aim of the present study was to evaluate the antibacterial and antioxidant activities of extracts and compounds from ludwigia leptocarpa, a plant traditionally used for its vermifugal, anti-dysenteric, and antimicrobial properties. a methanol extract was prepared by maceration of the dried plant and this was successively extracted with ethyl acetate to obtain ...201727431270
iridoids from canthium subcordatum iso-butanol fraction with potent biological activities.the continuous emergence of multi-drug-resistant bacteria drastically reduces the efficacy of antibiotic armory and, consequently, increases the frequency of therapeutic failure. the discovery of new antibacterial drugs is an urgent need. the present study reports the antibacterial and antioxidant activities of the methanol extract, fractions and iridoids from canthium subcordatum, a plant traditionally used as antidiabetic, anti-inflammatory, and antimicrobial.201728056944
vope, a vibrio cholerae type iii effector, attenuates the activation of cwi-mapk pathway in yeast model system.vope, a mitochondrial targeting t3ss effector protein of vibrio cholerae, perturbs innate immunity by modulating mitochondrial dynamics. in the current study, ectopic expression of vope was found to be toxic in a yeast model system and toxicity was further aggravated in the presence of various stressors. interestingly, a vope variant lacking predicted mitochondrial targeting sequence (mts) also exhibited partial lethality in the yeast system. with the aid of yeast genetic tools and different str ...201728373966
mechanisms for pseudoalteromonas piscicida-induced killing of vibrios and other bacterial pathogens.pseudoalteromonas piscicida are gram-negative gammaproteobacteria found in the marine environment. three strains of pigmented p. piscicida were isolated from seawater and partially characterized by inhibition studies, electron microscopy, and proteolytic enzyme production. growth inhibition and death occurred around colonies of p. piscicida on lawns of the naturally-occurring marine pathogens vibrio vulnificus, v. parahaemolyticus, v. cholerae, photobacterium damselae and shewanella algae inhibi ...201728363962
repair of a bacterial small β-barrel toxin pore depends on channel width.membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. here, we report the first paradigm of ca(2+)-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of photobacterium damselae subsp. damselae in striking contrast, vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair. mutational analysis uncovered a role of channel width in toxicity and repair. thus, the replacement ...201728196960
correlation of edge truncation with antibacterial activity of plate-like anisotropic silver nanoparticles.the effect of silver nanoparticle anisotropy on the antibacterial properties has been studied against escherichia coli, staphylococcus aureus, bacillus, vibrio cholerae, and streptococcus pyogenes. anisotropic silver nanoparticles have been synthesized by solvothermal process. the uv-visible absorption, x-ray diffraction, and tem studies show the anisotropic nature of silver nanoparticles. the results demonstrate that the anisotropic silver nanoparticles undergo a shape-dependent interaction wit ...201728707245
characterization of the escherichia coli concentrative nucleoside transporter nupc using computational, biochemical, and biophysical methods.members of the concentrative nucleoside transporter (cnt) family of proteins mediate uptake of nucleosides into cells driven by a cation gradient, which then enter salvage pathways for nucleic acid synthesis. in humans, they also transport hydrophilic anticancer and antiviral nucleoside analogue drugs into cells and tissues where they exert their pharmacological effects. escherichia coli cnt nupc (400 residues) is pyrimidine-specific and driven by a proton gradient. we have used computational, b ...201728682624
putative protein vc0395_0300 from vibrio cholerae is a diguanylate cyclase with a role in biofilm formation.the hallmark of the lifecycle of vibrio cholerae is its ability to switch between two lifestyles - the sessile, non-pathogenic form and the motile, infectious form in human hosts. one of these changes is in the formation of surface biofilms, when in sessile aquatic habitats. the cell-cell interactions within a v. cholerae biofilm are stabilized by the production of an exopolysachharide (eps) matrix, which in turn is regulated by the ubiquitous secondary messenger, cyclic di-gmp (c-di-gmp), synth ...201728647124
electrostatic interactions between the ctx phage minor coat protein and the bacterial host receptor tola drive the pathogenic conversion of vibrio cholerae.vibrio cholerae is a natural inhabitant of aquatic environments and converts to a pathogen upon infection by a filamentous phage, ctxφ, that transmits the cholera toxin-encoding genes. this toxigenic conversion of v. cholerae has evident implication in both genome plasticity and epidemic risk, but the early stages of the infection have not been thoroughly studied. ctxφ transit across the bacterial periplasm requires binding between the minor coat protein named piii and a bacterial inner-membrane ...201728642371
a versatile toolbox for the control of protein levels using n(ε)-acetyl-l-lysine dependent amber suppression.the analysis of the function of essential genes in vivo depends on the ability to experimentally modulate levels of their protein products. current methods to address this are based on transcriptional or post-transcriptional regulation of mrnas, but approaches based on the exploitation of translation regulation have so far been neglected. here we describe a toolbox, based on amber suppression in the presence of n(ε)-acetyl-l-lysine (ack), for translational tuning of protein output. we chose the ...201728594177
evaluation of synergy and bacterial regrowth in photocatalytic ozonation disinfection of municipal wastewater.the use of solar and ultraviolet titanium dioxide photocatalytic ozonation processes to inactivate waterborne pathogens (escherichia coli, salmonella species, shigella species and vibrio cholerae) in synthetic water and secondary municipal wastewater effluent is presented. the performance indicators were bacterial inactivation efficiency, post-disinfection regrowth and synergy effects (collaboration) between ozonation and photocatalysis (photocatalytic ozonation). photocatalytic ozonation effect ...201728577398
histo-blood group antigens as mediators of infections.the critical first step of a microbial infection is usually the attachment of pathogens to host cell glycans. targets on host tissues are in particular the histo-blood group antigens (hbgas), which are present in rich diversity in the mucus layer and on the underlying mucosa. recent structural and functional studies have revealed significant new insight into the molecular mechanisms, explaining why individuals with certain blood groups are at increased risk of some infections. the most prominent ...201728544984
structural studies of the periplasmic portion of the diguanylate cyclase cdgh from vibrio cholerae.cyclic diguanylate monophosphate (c-di-gmp) is a second messenger involved in bacterial signal transduction and produced by diguanylate cyclases (dgcs) generally containing highly variable periplasmic signal-recognition domains. cdgh is a dgc enzyme that regulates rugosity associated phenotypes in vibrio cholerae. cdgh has two n-terminal tandem periplasmic substrate-binding (pbpb) domains for its signal recognition; however, the role of the tandem pbpb domains remains unclear. here, we reported ...201728500346
rstb regulates expression of the photobacterium damselae subsp. damselae major virulence factors damselysin, phobalysin p and phobalysin c.the marine pathogenic bacterium photobacterium damselae subsp. damselae causes septicemia in marine animals and in humans. the pphdd1 plasmid-encoded hemolysins damselysin (dly) and phobalysin p (phlyp), and the chromosome-encoded hemolysin phobalysin c (phlyc) constitute its main virulence factors. however, the mechanisms by which expression of these three hemolysins is regulated remain unknown. here we report the isolation of a mini-tn10 transposon mutant which showed a strong impairment in it ...201728443076
repurposing a two-component system-based biosensor for the killing of vibrio cholerae.new strategies to control cholera are urgently needed. this study develops an in vitro proof-of-concept sense-and-kill system in a wild-type escherichia coli strain to target the causative pathogen vibrio cholerae using a synthetic biology approach. our engineered e. coli specifically detects v. cholerae via its quorum-sensing molecule cai-1 and responds by expressing the lysis protein yebf-art-085, thereby self-lysing to release the killing protein art-085 to kill v. cholerae. for this report, ...201728441472
great cormorants (phalacrocorax carbo) as potential vectors for the dispersal of vibrio cholerae.vibrio cholerae is the cause of cholera, a devastating epidemic and pandemic disease. despite its importance, the way of its global dissemination is unknown. v. cholerae is abundant in aquatic habitats and is known to be borne by copepods, chironomids and fishes. our aim was to determine if fish-eating birds act as vectors in the spread of v. cholerae by consuming infected fish. we determined the existence of v. cholerae in the microbiome of 5/7 wild cormorants' intestine. in three of these v. c ...201728801549
enhancing multiplex genome editing by natural transformation (mugent) via inactivation of ssdna exonucleases.recently, we described a method for multiplex genome editing by natural transformation (mugent). mutant constructs for mugent require large arms of homology (>2000 bp) surrounding each genome edit, which necessitates laborious in vitro dna splicing. in vibrio cholerae, we uncover that this requirement is due to cytoplasmic ssdna exonucleases, which inhibit natural transformation. in ssdna exonuclease mutants, one arm of homology can be reduced to as little as 40 bp while still promoting integrat ...201728575400
detection of eight foodborne bacterial pathogens by oligonucleotide array hybridization.simultaneous and rapid detection of multiple foodborne bacterial pathogens is important for the prevention of foodborne illnesses.201728713514
development of a novel rationally designed antibiotic to inhibit a nontraditional bacterial target.the search for new nontraditional targets is a high priority in antibiotic design today. bacterial membrane energetics based on sodium ion circulation offers potential alternative targets. the present work identifies the na(+)-translocating nadh:ubiquinone oxidoreductase (na(+)-nqr), a key respiratory enzyme in many microbial pathogens, as indispensible for the chlamydia trachomatis infectious process. infection by chlamydia trachomatis significantly increased first h(+) and then na(+) levels wi ...201728425301
use of serologic responses against enteropathogens to assess the impact of a point-of-use water filter: a randomized controlled trial in western province, rwanda.diarrhea is a leading contributor to childhood morbidity and mortality in sub-saharan africa. given the challenge of blinding most water, sanitation, and hygiene (wash) interventions, diarrheal disease outcome measures in wash intervention trials are subject to potential bias and misclassification. using the platform of a cluster-randomized controlled trial of a household-based drinking water filter in western province, rwanda, we assessed the impact of the drinking water filter on enteric seroc ...201728749764
antibacterial and antioxidant constituents of extracts of endophytic fungi isolated from ocimum basilicum var. thyrsiflora leaves.fourteen fungal endophytes were isolated from the ocimum basilicum var. thyrsiflora leaves collected from northern thailand. eight genera were identified including aspergillus, ascochyta, nigrospora, blastomyces, colletotrichum, exidia, clitopilus, and nomuraea. the antibacterial activity of crude extracts from all endophytic fungi was tested against nine human bacterial pathogens: staphylococcus aureus, staphylococcus epidermidis, bacillus subtilis, bacillus cereus, escherichia coli, klebsiella ...201728698913
identification and growth optimization of a marine bacillus dk1-sa11 having potential of producing broad spectrum antimicrobial compounds.control of harmful bacteria in food, aquaculture, pharmaceuticals, agriculture, hospitals and recreation water pools are of great global concern. marine bacteria are an enormous source of bio-controlling agents. the aim of this study was to identify and optimize the growth conditions including effect of different biotic and abiotic factors on antimicrobial activity of strain dk1-sa11 isolated from qingdao bay of china yellow sea. microscopic characterization, api® 20e and 50 chb kit base carbohy ...201728653930
prevalence of enteric infections among hospitalized patients in two referral hospitals in ghana.diarrhea is an important cause of morbidity and mortality worldwide. in africa and ghana in particular, it is estimated to contribute directly to 19 and 25% of pediatric mortality among children under 5 years, respectively.201728716138
antiprotozoal, antibacterial and antidiarrheal properties from the flowers of chiranthodendron pentadactylon and isolated flavonoids.chiranthodendron pentadactylon larreat. (sterculiaceae) is a mexican plant used in traditional medicine for the treatment of heart disease symptoms and infectious diarrhea.201728539715
plant-made virus-like particles bearing influenza hemagglutinin (ha) recapitulate early interactions of native influenza virions with human monocytes/macrophages.plant-made virus-like particles (vlp) bearing influenza virus hemagglutinins (ha) are novel vaccine candidates that induce cross-reactive humoral and poly-functional t cell responses. to better understand the mechanisms that underlie this broad immunogenicity we studied early interactions of vlps bearing either h1 (a/california/07/2009 (h1n1)) or h5 (a/indonesia/05/2005 (h5n1)) with a human monocytoid cell line (u-937 cells) and human monocyte-derived macrophages (mdms) as model antigen-presenti ...201728712489
heme proximal hydrogen bonding between his170 and asp132 plays an essential role in the heme degradation reaction of hutz from vibrio cholerae.hutz from vibrio cholerae is an enzyme that catalyzes the oxygen-dependent degradation of heme. the crystal structure of the homologous protein from helicobacter pylori, hugz, predicts that asp132 in hutz is located within hydrogen-bonding distance of the heme axial ligand his170. hydrogen bonding between his170 and asp132 appears to be disfavored in heme-degrading enzymes, because it can contribute to the imidazolate character of the axial histidine, as observed in most heme-containing peroxida ...201728481076
discovery of two bacterial nitric oxide-responsive proteins and their roles in bacterial biofilm regulation.bacterial biofilms form when bacteria adhere to a surface and produce an exopolysaccharide matrix ( costerton science 1999 , 284 , 1318 ; davies science 1998 , 280 , 295 ; flemming nat. rev. microbiol. 2010 , 8 , 623 ). because biofilms are resistant to antibiotics, they are problematic in many aspects of human health and welfare, causing, for instance, persistent fouling of medical implants such as catheters and artificial joints ( brunetto chimia 2008 , 62 , 249 ). they are responsible for chr ...201728605194
a novel role of listeria monocytogenes membrane vesicles in inhibition of autophagy and cell death.bacterial membrane vesicle (mv) production has been mainly studied in gram-negative species. in this study, we show that listeria monocytogenes, a gram-positive pathogen that causes the food-borne illness listeriosis, produces mvs both in vitro and in vivo. we found that a major virulence factor, the pore-forming hemolysin listeriolysin o (llo), is tightly associated with the mvs, where it resides in an oxidized, inactive state. previous studies have shown that llo may induce cell death and auto ...201728516064
the dnak chaperone uses different mechanisms to promote and inhibit replication of vibrio cholerae chromosome 2.replication of vibrio cholerae chromosome 2 (chr2) depends on molecular chaperone dnak to facilitate binding of the initiator (rctb) to the replication origin. the binding occurs at two kinds of site, 12-mers and 39-mers, which promote and inhibit replication, respectively. here we show that dnak employs different mechanisms to enhance the two kinds of binding. we found that mutations in rctb that reduce dnak binding also reduce 12-mer binding and initiation. the initiation defect is suppressed ...201728420739
regulation of acetyl-coa synthetase transcription by the crbs/r two-component system is conserved in genetically diverse environmental pathogens.the crbs/r two-component signal transduction system is a conserved regulatory mechanism through which specific gram-negative bacteria control acetate flux into primary metabolic pathways. crbs/r governs expression of acetyl-coa synthase (acsa), an enzyme that converts acetate to acetyl-coa, a metabolite at the nexus of the cell's most important energy-harvesting and biosynthetic reactions. during infection, bacteria can utilize this system to hijack host acetate metabolism and alter the course o ...201728542616
vibrio cholerae type 6 secretion system effector trafficking in target bacterial cells.the type 6 secretion system (t6ss) is used by many gram-negative bacterial species to deliver toxic effector proteins into nearby bacteria prey cells to kill or inhibit their growth. vgrg proteins are core conserved secretion substrates of the t6ss and one subset of t6ss effectors consists of vgrg proteins with c-terminal extension domains carrying various enzymatic activities. in vibrio cholerae, vgrg3 has a hydrolase extension domain and degrades peptidoglycan in the periplasm of target bacter ...201728808000
control of virulence gene transcription by indirect readout in vibrio cholerae and salmonella enterica serovar typhimurium.indirect readout mechanisms of transcription control rely on the recognition of dna shape by transcription factors (tfs). tfs may also employ a direct readout mechanism that involves the reading of the base sequence in the dna major groove at the binding site. tfs with winged helix-turn-helix (whth) motifs use an alpha helix to read the base sequence in the major groove while inserting a beta sheet 'wing' into the adjacent minor groove. such whth proteins are important regulators of virulence ge ...201728631437
evaluation of microplate immunocapture method for detection of vibrio cholerae, salmonella typhi and shigella flexneri from food.improved methods with better separation and concentration ability for detection of foodborne pathogens are in constant need. the aim of this study was to evaluate microplate immunocapture (ic) method for detection of salmonella typhi, shigella flexneri and vibrio cholerae from food samples to provide a better alternative to conventional culture based methods.201728851288
crystal structure of master biofilm regulator csgd regulatory domain reveals an atypical receiver domain.the master regulator csgd switches planktonic growth to biofilm formation by activating synthesis of curli fimbriae and cellulose in enterobacteriaceae. csgd was classified to be the luxr response regulatory family, while its cognate sensor histidine kinase has not been identified yet. csgd consists of a c-terminal dna binding domain and an n-terminal regulatory domain that provokes the upstream signal transduction to further modulate its function. we provide the crystal structure of salmonella ...201728758290
interbacterial predation as a strategy for dna acquisition in naturally competent bacteria.natural competence enables bacteria to take up exogenous dna. the evolutionary function of natural competence remains controversial, as imported dna can act as a source of substrates or can be integrated into the genome. exogenous homologous dna can also be used for genome repair. in this opinion article, we propose that predation of non-related neighbouring bacteria coupled with competence regulation might function as an active strategy for dna acquisition. competence-dependent kin-discriminate ...201728690319
environmental vibrios represent a source of antagonistic compounds that inhibit pathogenic vibrio cholerae and vibrio parahaemolyticus strains.with the overuse of antibiotics, many pathogens including vibrio cholerae and vibrio parahaemolyticus have evolved multidrug resistance making treatment more difficult. while understanding the mechanisms that underlie pathogenesis is crucial, knowledge of bacterial interactions of v. cholerae and v. parahaemolyticus could provide insight to their susceptibility outside of the human host. based on previous work showing competition among environmental strains, we predict that marine-derived bacter ...201728857444
modelling of growth kinetics of vibrio cholerae in presence of gold nanoparticles: effect of size and morphology.emergence of multiple drug resistant strains of pathogenic bacteria calls for new initiatives to combat infectious diseases. gold nanoparticles (aunps), because of their non-toxic nature and size/shape dependent optical properties, offer interesting possibility. here we report the antibacterial efficacy of aunps of different size and shape (auns10, auns100 and aunr10; the number indicating the diameter in nm; s stands for sphere and r for rod) against the classical (o395) and el tor (n16961) bio ...201728851910
transposon insertion site sequencing for synthetic lethal screening.transposon insertion site sequencing (tis) permits genome-wide, quantitative fitness assessment of individual genomic loci. in addition to the identification of essential genes in given growth conditions, tis enables the elucidation of genetic networks such as synthetic lethal or suppressor gene combinations. therefore, tis becomes an exceptionally powerful tool for the high-throughput determination of genotype-phenotype relationships in bacteria. here, we describe a protocol for the generation ...201728842874
highlights from this issue. 201728839876
extracellular-matrix-mediated osmotic pressure drives vibrio cholerae biofilm expansion and cheater exclusion.biofilms, surface-attached communities of bacteria encased in an extracellular matrix, are a major mode of bacterial life. how the material properties of the matrix contribute to biofilm growth and robustness is largely unexplored, in particular in response to environmental perturbations such as changes in osmotic pressure. here, using vibrio cholerae as our model organism, we show that during active cell growth, matrix production enables biofilm-dwelling bacterial cells to establish an osmotic ...201728835649
prediction of bacterial small rnas in the rsma (csra) and toxt pathways: a machine learning approach.small rnas (srnas) constitute an important class of post-transcriptional regulators that control critical cellular processes in bacteria. recent research using high-throughput transcriptomic approaches has led to a dramatic increase in the discovery of bacterial srnas. however, it is generally believed that the currently identified srnas constitute a limited subset of the bacterial srna repertoire. in several cases, srnas belonging to a specific class are already known and the challenge is to id ...201728830349
spermine inhibits vibrio cholerae biofilm formation through the nsps-mbaa polyamine signaling system.the aquatic bacterium and human intestinal pathogen, vibrio cholerae, senses and responds to a variety of environment-specific cues to regulate biofilm formation. specifically, the polyamines norspermidine and spermidine enhance and repress v. cholerae biofilm formation, respectively. these effects are relevant for understanding v. cholerae pathogenicity and are mediated through the periplasmic binding protein, nsps, and the transmembrane c-di-gmp phosphodiesterase mbaa. however, the levels of s ...201728827313
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