scholarly journals Vibrio cholerae LexA Coordinates CTX Prophage Gene Expression

2009 ◽  
Vol 191 (22) ◽  
pp. 6788-6795 ◽  
Author(s):  
Harvey H. Kimsey ◽  
Matthew K. Waldor
Keyword(s):  
Gene Expression ◽  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Single Site ◽  
Virion Production ◽  
Regulatory Circuit ◽  
Ctxφ Prophage ◽  
Gene Regulatory ◽  
Ctx Prophage ◽  
Operator Site

ABSTRACT The filamentous bacteriophage CTXΦ transmits the cholera toxin genes by infecting and lysogenizing its host, Vibrio cholerae. CTXΦ genes required for virion production initiate transcription from the strong P A promoter, which is dually repressed in lysogens by the phage-encoded repressor RstR and the host-encoded SOS repressor LexA. Here we identify the neighboring divergent rstR promoter, P R, and show that RstR both positively and negatively autoregulates its own expression from this promoter. LexA is absolutely required for RstR-mediated activation of P R transcription. RstR autoactivation occurs when RstR is bound to an operator site centered 60 bp upstream of the start of transcription, and the coactivator LexA is bound to a 16-bp SOS box centered at position −23.5, within the P R spacer region. Our results indicate that LexA, when bound to its single site in the CTXΦ prophage, both represses transcription from P A and coactivates transcription from the divergent P R. We propose that LexA coordinates P A and P R prophage transcription in a gene regulatory circuit. This circuit is predicted to display transient switch behavior upon induction of CTXΦ lysogens.

scholarly journals Comparative Genomic Analyses of the Vibrio Pathogenicity Island and Cholera Toxin Prophage Regions in Nonepidemic Serogroup Strains of Vibrio cholerae

2003 ◽  
Vol 69 (3) ◽  
pp. 1728-1738 ◽  
Author(s):  
Manrong Li ◽  
Mamuka Kotetishvili ◽  
Yuansha Chen ◽  
Shanmuga Sozhamannan
Keyword(s):  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Fragment Length Polymorphism ◽  
Pathogenicity Island ◽  
Filamentous Phage ◽  
Comparative Genomic ◽  
Genomic Analyses ◽  
Ctxφ Prophage ◽  
Horizontal Acquisition ◽  
Restriction Fragment Length

ABSTRACT Two major virulence factors are associated with epidemic strains (O1 and O139 serogroups) of Vibrio cholerae: cholera toxin encoded by the ctxAB genes and toxin-coregulated pilus encoded by the tcpA gene. The ctx genes reside in the genome of a filamentous phage (CTXφ), and the tcpA gene resides in a vibrio pathogenicity island (VPI) which has also been proposed to be a filamentous phage designated VPIφ. In order to determine the prevalence of horizontal transfer of VPI and CTXφ among nonepidemic (non-O1 and non-O139 serogroups) V. cholerae, 300 strains of both clinical and environmental origin were screened for the presence of tcpA and ctxAB. In this paper, we present the comparative genetic analyses of 11 nonepidemic serogroup strains which carry the VPI cluster. Seven of the 11 VPI+ strains have also acquired the CTXφ. Multilocus sequence typing and restriction fragment length polymorphism analyses of the VPI and CTXφ prophage regions revealed that the non-O1 and non-O139 strains were genetically diverse and clustered in lineages distinct from that of the epidemic strains. The left end of the VPI in the non-O1 and non-O139 strains exhibited extensive DNA rearrangements. In addition, several CTXφ prophage types characterized by novel repressor (rstR) and ctxAB genes and VPIs with novel tcpA genes were found in these strains. These data suggest that the potentially pathogenic, nonepidemic, non-O1 and non-O139 strains identified in our study most likely evolved by sequential horizontal acquisition of the VPI and CTXφ independently rather than by exchange of O-antigen biosynthesis regions in an existing epidemic strain.

scholarly journals A Genome-Wide Screen Reveals that the Vibrio cholerae Phosphoenolpyruvate Phosphotransferase System Modulates Virulence Gene Expression

2015 ◽  
Vol 83 (9) ◽  
pp. 3381-3395 ◽  
Author(s):  
Qiyao Wang ◽  
Yves A. Millet ◽  
Michael C. Chao ◽  
Jumpei Sasabe ◽  
Brigid M. Davis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Insertion Site ◽  
Virulence Gene ◽  
Loss Of Function ◽  
Phosphotransferase System ◽  
Content Type ◽  
Virulence Gene Expression ◽  
A Genome

Diverse environmental stimuli and a complex network of regulatory factors are known to modulate expression ofVibrio cholerae's principal virulence factors. However, there is relatively little known about how metabolic factors impinge upon the pathogen's well-characterized cascade of transcription factors that induce expression of cholera toxin and the toxin-coregulated pilus (TCP). Here, we used a transposon insertion site (TIS) sequencing-based strategy to identify new factors required for expression oftcpA, which encodes the major subunit of TCP, the organism's chief intestinal colonization factor. Besides identifying most of the genes known to modulatetcpAexpression, the screen yieldedptsIandptsH, which encode the enzyme I (EI) and Hpr components of theV. choleraephosphoenolpyruvate phosphotransferase system (PTS). In addition to reduced expression of TcpA, strains lacking EI, Hpr, or the associated EIIAGlcprotein produced less cholera toxin (CT) and had a diminished capacity to colonize the infant mouse intestine. The PTS modulates virulence gene expression by regulating expression oftcpPHandaphAB, which themselves control expression oftoxT, the central activator of virulence gene expression. One mechanism by which PTS promotes virulence gene expression appears to be by modulating the amounts of intracellular cyclic AMP (cAMP). Our findings reveal that theV. choleraePTS is an additional modulator of the ToxT regulon and demonstrate the potency of loss-of-function TIS sequencing screens for defining regulatory networks.

scholarly journals Evolution of Superinfection Immunity in Cluster A Mycobacteriophages

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Travis N. Mavrich ◽  
Graham F. Hatfull
Keyword(s):  
Gene Expression ◽  
Genetic Diversity ◽  
Defense Mechanism ◽  
Genetic Interactions ◽  
Form Complex ◽  
Lytic Gene ◽  
Regulatory Circuit ◽  
Gene Regulatory ◽  
Cluster A ◽  
Phage Growth

ABSTRACTTemperate phages encode an immunity system to control lytic gene expression during lysogeny. This gene regulatory circuit consists of multiple interacting genetic elements, and although it is essential for controlling phage growth, it is subject to conflicting evolutionary pressures. During superinfection of a lysogen, the prophage’s circuit interacts with the superinfecting phage’s circuit and prevents lytic growth if the two circuits are closely related. The circuitry is advantageous since it provides the prophage with a defense mechanism, but the circuitry is also disadvantageous since it limits the phage’s host range during superinfection. Evolutionarily related phages have divergent, orthogonal immunity systems that no longer interact and are heteroimmune, but we do not understand how immunity systems evolve new specificities. Here, we use a group of Cluster A mycobacteriophages that exhibit a spectrum of genetic diversity to examine how immunity system evolution impacts superinfection immunity. We show that phages with mesotypic (i.e., genetically related but distinct) immunity systems exhibit asymmetric and incomplete superinfection phenotypes. They form complex immunity networks instead of well-defined immunity groups, and mutations conferring escape (i.e., virulence) from homotypic or mesotypic immunity have various escape specificities. Thus, virulence and the evolution of new immune specificities are shaped by interactions with homotypic and mesotypic immunity systems.IMPORTANCEMany aspects regarding superinfection, immunity, virulence, and the evolution of immune specificities are poorly understood due to the lack of large collections of isolated and sequenced phages with a spectrum of genetic diversity. Using a genetically diverse collection of Cluster A phages, we show that the classical and relatively straightforward patterns of homoimmunity, heteroimmunity, and virulence result from interactions between homotypic and heterotypic phages at the extreme edges of an evolutionary continuum of immune specificities. Genetic interactions between mesotypic phages result in more complex mesoimmunity phenotypes and virulence profiles. These results highlight that the evolution of immune specificities can be shaped by homotypic and mesotypic interactions and may be more dynamic than previously considered.

scholarly journals Multilocus variable-number tandem repeat analysis of Vibrio cholerae O1 El Tor strains harbouring classical toxin B

2010 ◽  
Vol 59 (7) ◽  
pp. 763-769 ◽  
Author(s):  
Seon Young Choi ◽  
Je Hee Lee ◽  
Yoon-Seong Jeon ◽  
Hye Ri Lee ◽  
Eun Jin Kim ◽  
...  
Keyword(s):  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Tandem Repeat ◽  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Group Iii ◽  
Repeat Analysis ◽  
Group I ◽  
Ctx Prophage ◽  
El Tor

Atypical Vibrio cholerae O1 strains – hybrid strains (strains that cannot be classified either as El Tor or classical biotype) and altered strains (El Tor biotype strains that produce classical cholera toxin) – are currently prevalent in Asia and Africa. A total of 74 hybrid and altered strains that harboured classical cholera toxin were investigated by multilocus variable-number tandem repeat analysis (MLVA). The results showed that the hybrid/altered strains could be categorized into three groups and that they were distant from the El Tor strain responsible for the seventh cholera pandemic. Hybrid/altered strains with a tandem repeat of the classical CTX prophage on the small chromosome were divided into two MLVA groups (group I: Mozambique/Bangladesh group; group III: Vietnam group), and altered strains with the RS1–CTX prophage containing the El Tor type rstR and classical ctxB on the large chromosome were placed in two MLVA groups (group II: India/Bangladesh group; group III: India/Vietnam group).

scholarly journals A Membrane-Embedded Amino Acid Couples the SpoIIQ Channel Protein to Anti-Sigma Factor Transcriptional Repression during Bacillus subtilis Sporulation

2016 ◽  
Vol 198 (9) ◽  
pp. 1451-1463 ◽  
Author(s):  
Kelly A. Flanagan ◽  
Joseph D. Comber ◽  
Elizabeth Mearls ◽  
Colleen Fenton ◽  
Anna F. Wang Erickson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Amino Acid ◽  
Sigma Factor ◽  
Late Gene ◽  
Late Gene Expression ◽  
Gene Encoding ◽  
Content Type ◽  
Regulatory Circuit ◽  
Gene Regulatory

ABSTRACTSpoIIQ is an essential component of a channel connecting the developing forespore to the adjacent mother cell duringBacillus subtilissporulation. This channel is generally required for late gene expression in the forespore, including that directed by the late-acting sigma factor σG. Here, we present evidence that SpoIIQ also participates in a previously unknown gene regulatory circuit that specifically represses expression of the gene encoding the anti-sigma factor CsfB, a potent inhibitor of σG. ThecsfBgene is ordinarily transcribed in the forespore only by the early-acting sigma factor σF. However, in a mutant lacking the highly conserved SpoIIQ transmembrane amino acid Tyr-28,csfBwas also aberrantly transcribed later by σG, the very target of CsfB inhibition. This regulation ofcsfBby SpoIIQ Tyr-28 is specific, given that the expression of other σF-dependent genes was unaffected. Moreover, we identified a conserved element within thecsfBpromoter region that is both necessary and sufficient for SpoIIQ Tyr-28-mediated inhibition. These results indicate that SpoIIQ is a bifunctional protein that not only generally promotes σGactivity in the forespore as a channel component but also specifically maximizes σGactivity as part of a gene regulatory circuit that represses σG-dependent expression of its own inhibitor, CsfB. Finally, we demonstrate that SpoIIQ Tyr-28 is required for the proper localization and stability of the SpoIIE phosphatase, raising the possibility that these two multifunctional proteins cooperate to fine-tune developmental gene expression in the forespore at late times.IMPORTANCECellular development is orchestrated by gene regulatory networks that activate or repress developmental genes at the right time and place. Late gene expression in the developingBacillus subtilisspore is directed by the alternative sigma factor σG. The activity of σGrequires a channel apparatus through which the adjacent mother cell provides substrates that generally support gene expression. Here we report that the channel protein SpoIIQ also specifically maximizes σGactivity as part of a previously unknown regulatory circuit that prevents σGfrom activating transcription of the gene encoding its own inhibitor, the anti-sigma factor CsfB. The discovery of this regulatory circuit significantly expands our understanding of the gene regulatory network controlling late gene expression in the developingB. subtilisspore.

scholarly journals Activation of the Vibrio cholerae SOS Response Is Not Required for Intestinal Cholera Toxin Production or Colonization

2006 ◽  
Vol 74 (2) ◽  
pp. 927-930 ◽  
Author(s):  
Mariam Quinones ◽  
Brigid M. Davis ◽  
Matthew K. Waldor
Keyword(s):  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Sos Response ◽  
Toxin Production ◽  
Mrna Levels ◽  
Suckling Mouse ◽  
Potent Inducer ◽  
Genes Encoding ◽  
Mouse Intestine ◽  
Ctx Prophage

ABSTRACT Cholera toxin, one of the main virulence factors of Vibrio cholerae, is encoded in the genome of CTXφ, a V. cholerae-specific lysogenic filamentous bacteriophage. Although the genes encoding cholera toxin, ctxAB, are known to have their own promoter, the toxin genes can also be transcribed from an upstream CTXφ promoter, PrstA . The V. cholerae SOS response to DNA damage induces the CTX prophage by stimulating gene expression initiating from PrstA . Here, we investigated whether ctxA mRNA levels increase along with the levels of the transcripts for the other CTXφ genes following stimulation of the V. cholerae SOS response. Treatment of V. cholerae with the SOS-inducing agent mitomycin C increased the level of ctxA mRNA approximately sevenfold, apparently by augmenting the activity of PrstA . However, using suckling mice as a model host, we found that intraintestinal ctxA transcription does not depend on PrstA . In fact, the suckling mouse intestine does not appear to be a potent inducer of the V. cholerae SOS response. Furthermore, alleviation of LexA-mediated repression of the V. cholerae SOS regulon was not required for V. cholerae growth in the suckling mouse intestine. Our observations suggest that pathogenicity of V. cholerae does not depend on its SOS response.

scholarly journals Vibrio cholerae H-NS Silences Virulence Gene Expression at Multiple Steps in the ToxR Regulatory Cascade

2000 ◽  
Vol 182 (15) ◽  
pp. 4295-4303 ◽  
Author(s):  
Melinda B. Nye ◽  
James D. Pfau ◽  
Karen Skorupski ◽  
Ronald K. Taylor
Keyword(s):  
Gene Expression ◽  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Transcriptional Start Site ◽  
Regulatory Protein ◽  
Virulence Gene ◽  
Virulence Gene Expression ◽  
Activator Proteins ◽  
Regulatory Cascade ◽  
Genes Encoding

ABSTRACT H-NS is an abundant nucleoid-associated protein involved in the maintenance of chromosomal architecture in bacteria. H-NS also has a role in silencing the expression of a variety of environmentally regulated genes during growth under nonpermissive conditions. In this study we demonstrate a role for H-NS in the negative modulation of expression of several genes within the ToxR virulence regulon ofVibrio cholerae. Deletion of hns resulted in high, nearly constitutive levels of expression of the genes encoding cholera toxin, toxin-coregulated pilus, and the ToxT virulence gene regulatory protein. For the cholera toxin- and ToxT-encoding genes, elevated expression in an hns mutant was found to occur in the absence of the cognate activator proteins, suggesting that H-NS functions directly at these promoters to decrease gene expression. Deletion analysis of the region upstream of toxT suggests that an extensive region located far upstream of the transcriptional start site is required for complete H-NS-mediated repression of gene expression. These data indicate that H-NS negatively influences multiple levels of gene expression within the V. choleraevirulence cascade and raise the possibility that the transcriptional activator proteins in the ToxR regulon function to counteract the repressive effects of H-NS at the various promoters as well as to recruit RNA polymerase.

Classical RS1 and environmental RS1 elements in Vibrio cholerae O1 El Tor strains harbouring a tandem repeat of CTX prophage: revisiting Mozambique in 2005

2010 ◽  
Vol 59 (3) ◽  
pp. 302-308 ◽  
Author(s):  
Seon Young Choi ◽  
Je Hee Lee ◽  
Eun Jin Kim ◽  
Hye Ri Lee ◽  
Yoon-Seong Jeon ◽  
...  
Keyword(s):  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Tandem Repeat ◽  
Small Chromosome ◽  
Classical Type ◽  
Large Chromosome ◽  
New Type ◽  
Vibrio Cholerae O1 ◽  
Ctx Prophage ◽  
El Tor

Currently, Vibrio cholerae O1 serogroup biotype El Tor strains producing classical type cholera toxin (altered strains or El Tor variants) are prevalent in Asia and in Mozambique. Mozambican strains collected in 2004 contained a tandem repeat of CTX prophage on the small chromosome and each CTX prophage harboured the classical rstR and classical ctxB. We found that the majority of the strains collected in 2005 in Mozambique contained extra elements on the large chromosome in addition to the tandem repeat of CTX prophage on the small chromosome. New type RS1 elements RS1cla and RS1env, and a CTXenv with rstR env and the classical ctxB were identified on the large chromosome of the Mozambican isolates collected in 2005.

scholarly journals Recent Vibrio cholerae O1 Epidemic Strains Are Unable To Replicate CTXΦ Prophage Genome

mSphere ◽  
2021 ◽  
Author(s):  
Kaoru Ochi ◽  
Tamaki Mizuno ◽  
Prosenjit Samanta ◽  
Asish K. Mukhopadhyay ◽  
Shin-ichi Miyoshi ◽  
...  
Keyword(s):  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Diarrheal Disease ◽  
Content Type ◽  
Ctxφ Prophage ◽  
Vibrio Cholerae O1 ◽  
El Tor

Cholera is an acute diarrheal disease caused by pathogenic strains of V. cholerae generated by lysogenization of the filamentous cholera toxin phage CTXΦ. The analysis revealed that recent isolates possessed altered CTXΦ prophage array of prototype El Tor strain and were defective in replicating the CTXΦ genome.

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