Molecular mechanisms of virstatin resistance by non-O1/non-O139 strains of Vibrio cholerae.

Abstract:

:Virstatin is a previously described small molecule inhibitor of Vibrio cholerae virulence. We have demonstrated that the molecule inhibits the activity of the transcriptional activator ToxT, thereby preventing elaboration of the toxin co-regulated pilus (TCP) and cholera toxin in vitro and in vivo in O1 strains of V. cholerae. While strains of the O1 and O139 serogroups are the cause of most epidemic and endemic cholera currently seen globally, sporadic disease caused by strains of non-O1/non-O139 serogroups suggests that understanding the pathogenic mechanisms of these unusual strains is relevant for disease. Although some non-O1/non-O139 strains have acquired the pathogenicity island that encodes the TCP, the role that this essential colonization factor of O1/O139 strains plays in the virulence of non-O1/non-O139 strains has not been determined. In this study, we utilize virstatin in a 'chemical genetic approach' to examine the role of ToxT, and thus by inference TCP, in the colonization of a panel of predominantly non-O1/non-O139 tcp+ strains. We identified nine strains whose colonization was resistant to virstatin inhibition in the infant mouse model. These strains presumably colonize by a TCP-independent mechanism or contain a naturally occurring virstatin-resistant ToxT. Four strains contained the typical toxT gene found in O1/O139 strains (toxT(EPI)) isolated from cholera epidemics. Interruption of toxT in one of these strains did not affect colonization of the infant mouse small intestine. The remaining five strains were found to contain a sequence divergent toxT gene that has been previously designated toxT(ENV) because of its occurrence in isolates of V. cholerae from the environment. We show that ToxT(ENV) is resistant to virstatin in two separate heterologous systems and is necessary for efficient colonization of the infant mouse small intestine. These results support the new concept that chemical genetic probes for the in vivo function or expression of virulence genes can be used to identify strains that express alternative virulence factors or novel regulatory systems that are functional in vivo.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Shakhnovich EA,Sturtevant D,Mekalanos JJ

doi

10.1111/j.1365-2958.2007.05984.x

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1331-41

issue

6

eissn

0950-382X

issn

1365-2958

pii

MMI5984

journal_volume

66

pub_type

杂志文章
  • Retrotransposition strategies of the Lactococcus lactis Ll.LtrB group II intron are dictated by host identity and cellular environment.

    abstract::Group II introns are mobile retroelements that invade their cognate intron-minus gene in a process known as retrohoming. They can also retrotranspose to ectopic sites at low frequency. Previous studies of the Lactococcus lactis intron Ll.LtrB indicated that in its native host, as in Escherichia coli, retrohoming occur...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04554.x

    authors: Coros CJ,Landthaler M,Piazza CL,Beauregard A,Esposito D,Perutka J,Lambowitz AM,Belfort M

    更新日期:2005-04-01 00:00:00

  • Competitive activation of the Escherichia coli argO gene coding for an arginine exporter by the transcriptional regulators Lrp and ArgP.

    abstract::In vivo and in vitro analyses indicate that transcription of the argO gene coding for an arginine exporter is regulated by the global transcriptional regulator Lrp, an effect that went by unnoticed in previous genome-scale screenings of the Lrp regulatory network in Escherichia coli. Lrp activates the argO promoter fo...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06950.x

    authors: Peeters E,Nguyen Le Minh P,Foulquié-Moreno M,Charlier D

    更新日期:2009-12-01 00:00:00

  • The involvement of NAD(P)H dehydrogenase subunits, NdhD3 and NdhF3, in high-affinity CO2 uptake in Synechococcus sp. PCC7002 gives evidence for multiple NDH-1 complexes with specific roles in cyanobacteria.

    abstract::Random gene tagging was used to obtain new mutants of the marine cyanobacterium, Synechococcus sp. PCC7002, with defects in the CO2-concentrating mechanism (CCM). Two of these mutants, K22 and A41, showed poor growth at limiting CO2. Isolation and sequencing of a 6. 6 kb genomic region revealed the existence of five p...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1999.01457.x

    authors: Klughammer B,Sültemeyer D,Badger MR,Price GD

    更新日期:1999-06-01 00:00:00

  • Identification and functional analysis of the Rz/Rz1-like accessory lysis genes in the membrane-containing bacteriophage PRD1.

    abstract::Bacteriophage PRD1 is a tailless membrane-containing double-stranded (ds) DNA virus infecting a variety of Gram-negative bacteria. In order to affect cell lysis, like most dsDNA phages, PRD1 uses the holin-endolysin system. In this study, we identified two accessory lysis genes, XXXVI and XXXVII, coding for proteins P...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2008.06165.x

    authors: Krupovic M,Cvirkaite-Krupovic V,Bamford DH

    更新日期:2008-04-01 00:00:00

  • Transcriptome analysis of all two-component regulatory system mutants of Escherichia coli K-12.

    abstract::We have systematically examined the mRNA profiles of 36 two-component deletion mutants, which include all two-component regulatory systems of Escherichia coli, under a single growth condition. DNA microarray results revealed that the mutants belong to one of three groups based on their gene expression profiles in Luri...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2002.03170.x

    authors: Oshima T,Aiba H,Masuda Y,Kanaya S,Sugiura M,Wanner BL,Mori H,Mizuno T

    更新日期:2002-10-01 00:00:00

  • The MreB and Min cytoskeletal-like systems play independent roles in prokaryotic polar differentiation.

    abstract::Establishment of an axis of cell polarity and differentiation of the cell poles are fundamental aspects of cellular development in many organisms. We compared the effects of two bacterial cytoskeletal-like systems, the MreB and MinCDE systems, on these processes in Escherichia coli. We report that the Min proteins are...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04841.x

    authors: Shih YL,Kawagishi I,Rothfield L

    更新日期:2005-11-01 00:00:00

  • Crl stimulates RpoS activity during stationary phase.

    abstract::RpoS, an alternative primary sigma factor, has been shown to be regulated at multiple levels, including transcription, translation and protein stability. Here, we present evidence that suggests that RpoS is regulated at yet another level by the product of the crl gene. The crl gene was first thought to encode the majo...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1998.01007.x

    authors: Pratt LA,Silhavy TJ

    更新日期:1998-09-01 00:00:00

  • The link between 20S proteasome activity and post-replication DNA repair in Saccharomyces cerevisiae.

    abstract::We have shown previously that deletion of the Saccharomyces cerevisiae UMP1 gene encoding the 20S proteasome maturase causes sensitivity to UV radiation. In the current report, we have extended this finding to show that mutations specifically compromising chymotrypsin-like or trypsin-like activity of 20S proteasome pe...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.03635.x

    authors: Podlaska A,McIntyre J,Skoneczna A,Sledziewska-Gojska E

    更新日期:2003-09-01 00:00:00

  • Self-compartmentalized bacterial proteases and pathogenesis.

    abstract::Protein degradation is required for homeostasis of all living organisms. Self-compartmentalized ATP-dependent proteases are required for virulence of several pathogenic bacteria. Among the proteases implicated are ClpP and Lon, as well as the more recently identified bacterial proteasome. It is generally assumed that ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2958.2006.05128.x

    authors: Butler SM,Festa RA,Pearce MJ,Darwin KH

    更新日期:2006-05-01 00:00:00

  • An acetylatable lysine controls CRP function in E. coli.

    abstract::Transcriptional regulation is the key to ensuring that proteins are expressed at the proper time and the proper amount. In Escherichia coli, the transcription factor cAMP receptor protein (CRP) is responsible for much of this regulation. Questions remain, however, regarding the regulation of CRP activity itself. Here,...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.13874

    authors: Davis R,Écija-Conesa A,Gallego-Jara J,de Diego T,Filippova EV,Kuffel G,Anderson WF,Gibson BW,Schilling B,Canovas M,Wolfe AJ

    更新日期:2018-01-01 00:00:00

  • The essential cell division protein FtsN contains a critical disulfide bond in a non-essential domain.

    abstract::Disulfide bonds are found in many proteins associated with the cell wall of Escherichia coli, and for some of these proteins the disulfide bond is critical to their stability and function. One protein found to contain a disulfide bond is the essential cell division protein FtsN, but the importance of this bond to the ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.13565

    authors: Meehan BM,Landeta C,Boyd D,Beckwith J

    更新日期:2017-02-01 00:00:00

  • Controlling pore assembly of staphylococcal gamma-haemolysin by low temperature and by disulphide bond formation in double-cysteine LukF mutants.

    abstract::Staphylococcal LukF and Hlg2 are water-soluble monomers of gamma-haemolysin that assemble into oligomeric pores on the erythrocyte membranes. Here, we have created double-cysteine LukF mutants, in which single disulphide bonds connect either the prestem domain and the cap domain (V12C-T136C, Cap-Stem), or two beta-str...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2002.03125.x

    authors: Nguyen VT,Higuchi H,Kamio Y

    更新日期:2002-09-01 00:00:00

  • The virulence protein Yop5 of Yersinia pseudotuberculosis is regulated at transcriptional level by plasmid-plB1 -encoded trans-acting elements controlled by temperature and calcium.

    abstract::The DNA sequence of the structural gene (yopE) of one of the Yersinia pseudotuberculosis virulence plas-mid-plB1-encoded proteins, Yop5, is presented. The deduced protein showed a molecular weight of 22971 Daltons. A specific mutant, having a kanamycin-resistance fragment inserted within the yopE gene was no longer vi...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1988.tb00013.x

    authors: Forsberg A,Wolf-Watz H

    更新日期:1988-01-01 00:00:00

  • Regulation of plasmid R1 replication: PcnB and RNase E expedite the decay of the antisense RNA, CopA.

    abstract::The replication frequency of plasmid R1 is controlled by an unstable antisense RNA, CopA, which, by binding to its complementary target, blocks translation of the replication rate-limiting protein RepA. Since the degree of inhibition is directly correlated with the intracellular concentration of CopA, factors affectin...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1997.5871953.x

    authors: Söderbom F,Binnie U,Masters M,Wagner EG

    更新日期:1997-11-01 00:00:00

  • The terminal oxidases of Paracoccus denitrificans.

    abstract::Three distinct types of terminal oxidases participate in the aerobic respiratory pathways of Paracoccus denitrificans. Two alternative genes encoding subunit I of the aa3-type cytochrome c oxidase have been isolated before, namely ctaDI and ctaDII. Each of these genes can be expressed separately to complement a double...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb00414.x

    authors: de Gier JW,Lübben M,Reijnders WN,Tipker CA,Slotboom DJ,van Spanning RJ,Stouthamer AH,van der Oost J

    更新日期:1994-07-01 00:00:00

  • Structural and genetic analysis of the bvg locus in Bordetella species.

    abstract::The bvg locus contains two genes, bvgA and bvgS, which control the expression of the virulence-associated genes in Bordetella species by a system similar to the two-component systems used by a variety of bacterial species to respond to environmental stimuli. We determined the nucleotide sequence of the bvg loci of Bor...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1991.tb02093.x

    authors: Aricò B,Scarlato V,Monack DM,Falkow S,Rappuoli R

    更新日期:1991-10-01 00:00:00

  • IHF redistributes bound initiator protein, DnaA, on supercoiled oriC of Escherichia coli.

    abstract::In Escherichia coli, initiation of chromosome replication requires that DnaA binds to R boxes (9-mer repeats) in oriC, the unique chromosomal replication origin. At the time of initiation, integration host factor (IHF) also binds to a specific site in oriC. IHF stimulates open complex formation by DnaA on supercoiled ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2000.01755.x

    authors: Grimwade JE,Ryan VT,Leonard AC

    更新日期:2000-02-01 00:00:00

  • A tertiary structural element in S box leader RNAs is required for S-adenosylmethionine-directed transcription termination.

    abstract::The S box transcription termination control system regulates expression of genes involved in methionine metabolism. Expression of the S box regulon, comprised of 11 transcriptional units in Bacillus subtilis, is induced in response to starvation for methionine. We previously demonstrated that S-adenosylmethionine (SAM...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04740.x

    authors: McDaniel BA,Grundy FJ,Henkin TM

    更新日期:2005-08-01 00:00:00

  • Structural and functional diversity among bacterial interspersed mosaic elements (BIMEs).

    abstract::Palindromic units (PU or REP) were defined as 40-nucleotide DNA sequences which are highly repeated in the genome of several members of the Enterobacteriaceae. They were shown to be a constituent of the bacterial interspersed mosaic element (BIME), in which they are associated with other repetitive sequences. We repor...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb00995.x

    authors: Bachellier S,Saurin W,Perrin D,Hofnung M,Gilson E

    更新日期:1994-04-01 00:00:00

  • Evidence that F-plasmid proteins TraV, TraK and TraB assemble into an envelope-spanning structure in Escherichia coli.

    abstract::We have examined the role of the F-plasmid TraV outer membrane lipoprotein in the assembly of F-pili. Yeast two-hybrid analysis with a traV bait repeatedly identified traK, which is predicted to encode a periplasmic protein, among positive prey plasmids. A traK bait in turn identified traV and traB, which is predicted...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2001.02667.x

    authors: Harris RL,Hombs V,Silverman PM

    更新日期:2001-11-01 00:00:00

  • Multiple stress signal integration in the regulation of the complex sigma S-dependent csiD-ygaF-gabDTP operon in Escherichia coli.

    abstract::The csiD-ygaF-gabDTP region in the Escherichia coli genome represents a cluster of sigma S-controlled genes. Here, we investigated promoter structures, sigma factor dependencies, potential co-regulation and environmental regulatory patterns for all of these genes. We find that this region constitutes a complex operon ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.03867.x

    authors: Metzner M,Germer J,Hengge R

    更新日期:2004-02-01 00:00:00

  • Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses.

    abstract::Prokaryotic toxin - antitoxin (TA) loci encode mRNA interferases that inhibit translation, either by cleaving mRNA codons at the ribosomal A site or by cleaving any RNA site-specifically. So far, seven mRNA interferases of Escherichia coli have been identified, four of which cleave mRNA by a translation-dependent mech...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06969.x

    authors: Christensen-Dalsgaard M,Jørgensen MG,Gerdes K

    更新日期:2010-01-01 00:00:00

  • Transcriptional regulation of bioluminesence genes from Vibrio fischeri.

    abstract::The phenomenon of cell-density-dependent control of gene expression, called autoinduction, has long been a subject of interest and investigation in bioluminescent marine bacteria. It is now becoming clear that many other bacteria, including animal and plant pathogens, use an autoinduction mechanism to regulate a varie...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2958.1995.mmi_17050801.x

    authors: Sitnikov DM,Schineller JB,Baldwin TO

    更新日期:1995-09-01 00:00:00

  • DnaA coordinates replication initiation and cell cycle transcription in Caulobacter crescentus.

    abstract::The level of DnaA, a key bacterial DNA replication initiation factor, increases during the Caulobacter swarmer-to-stalked transition just before the G1/S transition. We show that DnaA coordinates DNA replication initiation with cell cycle progression by acting as a global transcription factor. Using DnaA depletion and...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04912.x

    authors: Hottes AK,Shapiro L,McAdams HH

    更新日期:2005-12-01 00:00:00

  • Synthetic growth phenotypes of Escherichia coli lacking ppGpp and transketolase A (tktA) are due to ppGpp-mediated transcriptional regulation of tktB.

    abstract::Many physiological adjustments to nutrient changes involve ppGpp. Recent attempts to deduce ppGpp regulatory effects using proteomics or gene profiling can rigorously identify proteins or transcripts, but the functional significance is often unclear. Using a random screen for synthetic lethals we found a ppGpp-depende...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2008.06317.x

    authors: Harinarayanan R,Murphy H,Cashel M

    更新日期:2008-08-01 00:00:00

  • Role of the spacer between the -35 and -10 regions in sigmas promoter selectivity in Escherichia coli.

    abstract::In vitro, the sigma(s) subunit of RNA polymerase (RNAP), RpoS, recognizes nearly identical -35 and -10 promoter consensus sequences as the vegetative sigma70. In vivo, promoter selectivity of RNAP holoenzyme containing either sigma(s) (Esigma(s)) or sigma70 (Esigma70) seems to be achieved by the differential ability o...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04998.x

    authors: Typas A,Hengge R

    更新日期:2006-02-01 00:00:00

  • Two sources of endogenous hydrogen peroxide in Escherichia coli.

    abstract::Mechanisms of hydrogen peroxide generation in Escherichia coli were investigated using a strain lacking scavenging enzymes. Surprisingly, the deletion of many abundant flavoenzymes that are known to autoxidize in vitro did not substantially lessen overall H(2)O(2) formation. However, H(2)O(2) production diminished by ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2010.07059.x

    authors: Korshunov S,Imlay JA

    更新日期:2010-03-01 00:00:00

  • Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase.

    abstract::Toxin-antitoxin loci have been identified in almost all free-living prokaryotes, often in high copy numbers. The biological function and molecular targets of the abundant vapBC loci are not yet known. Here we analyse the vapBC loci of Salmonella LT2 and Shigella plasmid pMYSH6000. Both loci encode putative PIN (PilT N...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2009.06694.x

    authors: Winther KS,Gerdes K

    更新日期:2009-05-01 00:00:00

  • A rainbow coalition of lipid transcriptional regulators.

    abstract::Lipids are essential structural constituents of bacterial cell membranes and walls, and their biosynthetic pathways are stringently regulated at both biochemical and genetic levels. The recent surge of new information about transcriptional regulation of bacterial lipid metabolism is highlighted by two studies in this ...

    journal_title:Molecular microbiology

    pub_type: 评论,杂志文章

    doi:

    authors: Zhang YM,Rock CO

    更新日期:2010-10-01 00:00:00

  • The chemosensory systems of Vibrio cholerae.

    abstract::Vibrio cholerae, the causative agent of the acute diarrheal disease cholera, is able to thrive in diverse habitats such as natural water bodies and inside human hosts. To ensure their survival, these bacteria rely on chemosensory pathways to sense and respond to changing environmental conditions. These pathways consti...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/mmi.14520

    authors: Ortega DR,Kjaer A,Briegel A

    更新日期:2020-09-01 00:00:00