The multiple antibiotic resistance (mar) operon of Escherichia coli is a paradigm for chromosomally encoded in enteric bacteria. locus recognised its ability to modulate efflux pump and porin expression via two transcription factors, MarR MarA. Here we map binding these regulators across the E. genome identify an extensive mar regulon. Most notably, MarA activates genes required DNA repair lipid trafficking. Consequently, reduces quinolone-induced damage tetracyclines traverse outer...

The histone-like nucleoid structuring (H-NS) protein is a DNA binding factor, found in gammaproteobacteria, with functional equivalents diverse microbes. Universally, such proteins are understood to silence transcription of horizontally acquired genes. Here, we identify transposon capture as major overlooked function H-NS. Using genome-scale approaches, show that H-NS bound regions transposition "hotspots". Since often interacts pathogenicity islands, targeting creates clinically relevant...

The bacterium

Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhoea in humans and neonatal farm animals. Annually, 380,000 human deaths, multi-million dollar losses the farming industry, can be attributed to ETEC infections. Illness results from action of enterotoxins, which disrupt signalling pathways that manage water electrolyte homeostasis mammalian gut. The resulting fluid loss is treated by oral rehydration. Hence, aqueous solutions glucose salt are ingested patient. Given central role...

Many bacteria use population density to control gene expression via quorum sensing. In Vibrio cholerae, sensing coordinates virulence, biofilm formation, and DNA uptake by natural competence. The transcription factors AphA HapR, expressed at low high cell respectively, play a key role. particular, triggers the entire virulence cascade upon host colonisation. this work we have mapped genome-wide binding AphA. We show that is versatile, exhibiting distinct modes of promoter regulation....

Many bacteria use quorum sensing to control changes in lifestyle. The process is regulated by microbially derived 'autoinducer' signalling molecules, that accumulate the local environment. Individual cells sense autoinducer abundance, infer population density, and alter their behaviour accordingly. In Vibrio cholerae, quorum-sensing signals are transduced phosphorelay transcription factor LuxO. Unphosphorylated LuxO permits expression of HapR, which alters global gene patterns. this work, we...

A commonly accepted paradigm of molecular biology is that transcription factors control gene expression by binding sites at the 5' end a gene. However, there growing evidence factor targets can occur within genes or between convergent genes. In this work, we have investigated one such target for cyclic AMP receptor protein (CRP) enterotoxigenic Escherichia coli. We show CRP binds two When bound, regulates small open reading frame, which term aatS, embedded adjacent Our work demonstrates...

Bacterial pathogens use a wide array of virulence factors to colonise and subsequently elicit disease in their host. These are often subject extensive regulation at the transcriptional level, ensure that expression is timely. Although many bespoke transcription primarily target genes, global also sometimes play role controlling these genes. Enteroaggregative Escherichia coli (EAEC) significant cause watery mucoid diarrhoea globally. The organism colonises small intestine before producing...

Bacterial small RNAs (sRNAs) are well known to modulate gene expression by base pairing with trans-encoded transcripts and typically non-coding. However, several sRNAs have been reported also contain an open reading frame thus considered dual-function RNAs. In this study, we discovered a RNA from Vibrio cholerae, called VcdRP, harboring 29 amino acid protein (VcdP), as base-pairing sequence. Using forward genetic screen, identified VcdRP repressor of cholera toxin production link phenotype...

The closely related transcription factors MarA, SoxS, Rob and RamA control overlapping stress responses in many enteric bacteria. Furthermore, constitutive expression of such regulators is linked to clinical antibiotic resistance. In this work we have mapped the binding across Salmonella Typhimurium genome. parallel, monitored changes start site use resulting from regulators. Together, these data allow direct indirect gene regulatory effects be disentangled. Promoter architecture regulon can...

Summary Enteroaggregative Escherichia coli (EAEC), is a diarrhoeagenic human pathogen commonly isolated from patients in both developing and industrialized countries. Pathogenic EAEC strains possess many virulence determinants, which are thought to be involved causing disease, though, the exact mechanism by causes diarrhoea unclear. Typical transcriptional regulator, AggR, controls expression of including attachment adherence fimbriae (AAF) that necessary for gut epithelial cells. Here,...

Bacterial cells and their associated plasmids bacteriophages encode numerous small proteins of unknown function. One example, the 73-amino-acid protein TraR, is encoded by transfer operon conjugative F plasmid Escherichia coli. TraR a distant homolog DksA, found in almost all proteobacterial species that required for ppGpp to regulate transcription during stringent response. DksA increase or decrease initiation depending on kinetic features promoter binding directly RNA polymerase without...

Abstract Many bacteria use cyclic dimeric guanosine monophosphate (c-di-GMP) to control changes in lifestyle. The molecule, synthesized by proteins having diguanylate cyclase activity, is often a signal transition from motile sedentary behaviour. In Vibrio cholerae, c-di-GMP can exert its effects via the transcription factors VpsT and VpsR. Together, these activate genes needed for V. cholerae form biofilms. this work, we have mapped genome-wide distribution of search further regulatory...

Transcription of the DNA template, to generate an RNA message, is first step in gene expression. The process initiates at sequences called promoters. Conventionally, promoters have been considered drive transcription a specific direction. However, recent work, we showed that many prokaryotic can divergent transcription. This consequence key for initiation being inherently symmetrical. Here, used global start site mapping determine prevalence such bidirectional Salmonella Typhimurium....

ABSTRACT Many bacteria use population density to control gene expression via quorum sensing. In Vibrio cholerae , sensing coordinates virulence, biofilm formation, and DNA uptake by natural competence. The transcription factors AphA HapR, expressed at low- high-cell respectively, play a key role. particular, triggers the entire virulence cascade upon host colonisation. this work we have mapped genome-wide binding AphA. We show that is versatile, exhibiting distinct modes of promoter...

Abstract Many bacteria use quorum sensing to control changes in lifestyle. The process is regulated by microbially derived “autoinducer” signalling molecules, that accumulate the local environment. Individual cells sense autoinducer abundance, infer population density, and alter their behaviour accordingly. In Vibrio cholerae, signals are transduced phosphorelay transcription factor LuxO. Unphosphorylated LuxO permits expression of HapR, which alters global gene patterns. this work, we have...

Many bacteria use quorum sensing to control changes in lifestyle. The process is regulated by microbially derived ‘autoinducer’ signalling molecules, that accumulate the local environment. Individual cells sense autoinducer abundance, infer population density, and alter their behaviour accordingly. In Vibrio cholerae , quorum-sensing signals are transduced phosphorelay transcription factor LuxO. Unphosphorylated LuxO permits expression of HapR, which alters global gene patterns. this work,...

The histone-like nucleoid structuring (H-NS) protein is a DNA binding factor, found in γ-proteobacteria, with functional equivalents diverse microbes. Universally, such proteins are understood to silence transcription of horizontally acquired genes. Here, we identify transposon capture as major overlooked function H-NS. Using genome scale approaches, show that H NS bound chromosomal regions transposition "hotspots". Since H-NS often interacts pathogenicity islands, targeting creates...

ABSTRACT Many bacteria use quorum sensing to control changes in lifestyle. The process is regulated by microbially derived “autoinducer” signalling molecules, that accumulate the local environment. Individual cells sense autoinducer abundance, infer population density, and alter their behaviour accordingly. In Vibrio cholerae , signals are transduced phosphorelay transcription factor LuxO. Unphosphorylated LuxO permits expression of HapR, which alters global gene patterns. this work, we have...

Many bacteria use quorum sensing to control changes in lifestyle. The process is regulated by microbially derived “autoinducer” signalling molecules, that accumulate the local environment. Individual cells sense autoinducer abundance, infer population density, and alter their behaviour accordingly. In Vibrio cholerae , signals are transduced phosphorelay transcription factor LuxO. Unphosphorylated LuxO permits expression of HapR, which alters global gene patterns. this work, we have mapped...

Biofilm formation is an important stage of the Vibrio cholerae lifecycle. The transcription factor VpsT a master regulator biofilm that activates expression matrix components in response to elevated intracellular c-di-GMP. has also been shown repress rpoSand genes involved motility. This suggests may have wider role transition from motile sessile lifestyle. To better understand V. lifestyle switching ChIP-seq (chromatin immunoprecipitation and DNA sequencing) was used map binding across...