Co‐ordination of pathogenicity island expression by the BipA GTPase in enteropathogenic <i>Escherichia coli</i> (EPEC)

Grant, A.; Farris, Michele; Alefounder, Peter R.; Williams, Peter H.; Woodward, Martin J.; O’Connor, C. David

doi:10.1046/j.1365-2958.2003.t01-1-03447.x

Cited by 106 publications

(86 citation statements)

References 53 publications

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“…Therefore, this is not a general effect on all promoters arising from the ability of Fis to influence DNA topology. Our discovery that Fis regulates the expression of all three type III secretion systems in Salmonella is in keeping with other studies that have pointed to regulatory overlaps between virulence genes and flagella in Salmonella (Eichelberg & Galan, 2000;Ellermeier & Slauch, 2003;Lawhon et al, 2003) and other bacteria (Goodier & Ahmer, 2001;Grant et al, 2003). The effect of Fis on murein lipoprotein expression is also relevant here, since the lpp gene product is a structural component of the cell envelope.…”

Section: Discussionsupporting

confidence: 68%

A global role for Fis in the transcriptional control of metabolism and type III secretion in Salmonella enterica serovar Typhimurium

et al. 2004

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Fis is a key DNA-binding protein involved in nucleoid organization and modulation of many DNA transactions, including transcription in enteric bacteria. The regulon of genes whose expression is influenced by Fis in Salmonella enterica serovar Typhimurium (S. typhimurium) has been defined by DNA microarray analysis. These data suggest that Fis plays a central role in coordinating the expression of both metabolic and type III secretion factors. The genes that were most strongly up-regulated by Fis were those involved in virulence and located in the pathogenicity islands SPI-1, SPI-2, SPI-3 and SPI-5. Similarly, motility and flagellar genes required Fis for full expression. This was shown to be a direct effect as purified Fis protein bound to the promoter regions of representative flagella and SPI-2 genes. Genes contributing to aspects of metabolism known to assist the bacterium during survival in the mammalian gut were also Fis-regulated, usually negatively. This category included components of metabolic pathways for propanediol utilization, biotin synthesis, vitamin B 12 transport, fatty acids and acetate metabolism, as well as genes for the glyoxylate bypass of the tricarboxylic acid cycle. Genes found to be positively regulated by Fis included those for ethanolamine utilization. The data reported reveal the central role played by Fis in coordinating the expression of both housekeeping and virulence factors required by S. typhimurium during life in the gut lumen or during systemic infection of host cells. INTRODUCTIONSalmonella enterica serovar Typhimurium (S. typhimurium) is the most common and best studied of the S. enterica serovars that infect humans (Finlay & Brumell, 2000). It is able to infect a range of animal species, including chicken, cattle and mice, and intensive study of this organism is providing important insights into key processes involved in bacterial pathogenesis. In the mouse, S. typhimurium is a facultative intracellular pathogen capable of invading epithelial cells and it has the ability to survive and proliferate within macrophages. The bacterium can be manipulated genetically with relative ease and the complete genome sequence is available (McClelland et al., 2001), allowing a combination of genetic analysis, cell biology and animal infection studies. This multidisciplinary approach has provided a picture of the major events involved when S. typhimurium infects the murine host. Following ingestion and passage through the stomach, the bacteria cross the lining of the intestine by invading the intestinal epithelium, predominantly via M cells. The Salmonellae are subsequently phagocytosed by macrophages before entering the blood stream and establishing a systemic infection (Finlay & Brumell, 2000; Galán, 2001;Groisman & Mouslim, 2000;Holden, 2002;Scherer & Miller, 2001).S. typhimurium is dependent upon the products of a large number of genes (up to 200) to cause infection (Finlay & Brumell, 2000). Some of the virulence genes are located on a 90 kb pathogenicity plasmid, of which the spv gen...

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Section: Discussionsupporting

confidence: 68%

A global role for Fis in the transcriptional control of metabolism and type III secretion in Salmonella enterica serovar Typhimurium

et al. 2004

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“…Although we could not clarify its mechanism of action, aurodox inhibited the secretion of some LEE-encoded proteins (EspA, EspB, EspD, EspF and Map) and EspC, a member of the immunoglobulin A protease family of autotransporters (Figure 3). It is known that the expression of LEE-encoded proteins and EspC is coordinately regulated by an LEE-encoded regulator, Ler, 28 and a BipA regulator, 29 a member of the ribosome binding GTPase family. Such findings suggest that aurodox inhibits the expression of genes under the control of Ler and/or BipA.…”

Section: Discussionmentioning

confidence: 99%

A small-molecule inhibitor of the bacterial type III secretion system protects against in vivo infection with Citrobacter rodentium

et al. 2010

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The type III secretion system (T3SS) is highly conserved in many Gram-negative pathogenic bacteria and functions as an injector of bacterial proteins (effectors) into host cells. T3SSs are involved in establishing disease processes, but this machinery is not essential for bacterial growth or homeostasis. Thus, T3SS is expected to be a candidate therapeutic target, and inhibitors of T3SSs could potentially reduce virulence without causing bacterial death, thereby avoiding any subsequent development of resistance. We identified a linear polyketide compound, aurodox, as a specific T3SS inhibitor from the culture broth of Streptomyces sp. using a screening system for the T3SS-mediated hemolysis of enteropathogenic Escherichia coli (EPEC) established by our group. Aurodox strongly inhibited T3SS-mediated hemolysis with an IC 50 value of 1.5 lg ml À1 without affecting bacterial growth in liquid media. We also demonstrated that aurodox specifically inhibits the secretion of type IIIsecreted proteins such as EspB, EspF and Map, without affecting the expression of the housekeeping protein GroEL. Furthermore, an in vivo infection study using mice clearly indicated that the administration of aurodox allowed the mice to survive a lethal dose of Citrobactor rodentium, a model bacterium for human pathogens such as EPEC. Thus, our in vivo study directly demonstrated for the first time that this putative T3SS inhibitor can be applied as a novel class of anti-infective agents.

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“…BipA has been shown to function as a master regulator by transcriptselective translational control (88). In E. coli, it is a master regulator of growth at low temperatures (91) and of the expression of genes in pathogenicity islands (43). Considering the conservation of domain arrangement and the 71% amino acid sequence identity between E. coli and P. putida BipA, we concluded that in P. putida BipA has a key role in adaptation to cold stress and growth at 4°C due to transcript-selective translation control.…”

Section: Indicated By Rt/pcr)mentioning

confidence: 99%

Functional Genomics of Stress Response in Pseudomonas putida KT2440

et al. 2006

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The metabolically versatile soil bacterium Pseudomonas putida has to cope with numerous abiotic stresses in its habitats. The stress responses of P. putida KT2440 to 4°C, pH 4.5, 0.8 M urea, and 45 mM sodium benzoate were analyzed by determining the global mRNA expression profiles and screening for stress-intolerant nonauxotrophic Tn5 transposon mutants. In 392 regulated genes or operons, 36 gene regions were differentially expressed by more than 2.5-fold, and 32 genes in 23 operons were found to be indispensable for growth during exposure to one of the abiotic stresses. The transcriptomes of the responses to urea, benzoate, and 4°C correlated positively with each other but negatively with the transcriptome of the mineral acid response. The CbrAB sensor kinase, the cysteine synthase CysM, PcnB and VacB, which control mRNA stability, and BipA, which exerts transcript-specific translational control, were essential to cope with cold stress. The cyo operon was required to cope with acid stress. A functional PhoP, PtsP, RelA/SpoT modulon, and adhesion protein LapA were necessary for growth in the presence of urea, and the outer membrane proteins OmlA and FepA and the phosphate transporter PstBACS were indispensable for growth in the presence of benzoate. A lipid A acyltransferase (PP0063) was a mandatory component of the stress responses to cold, mineral acid, and benzoate. Adaptation of the membrane barrier, uptake of phosphate, maintenance of the intracellular pH and redox status, and translational control of metabolism are key mechanisms of the response of P. putida to abiotic stresses.

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Co‐ordination of pathogenicity island expression by the BipA GTPase in enteropathogenic Escherichia coli (EPEC)

Cited by 106 publications

References 53 publications

A global role for Fis in the transcriptional control of metabolism and type III secretion in Salmonella enterica serovar Typhimurium

A global role for Fis in the transcriptional control of metabolism and type III secretion in Salmonella enterica serovar Typhimurium

A small-molecule inhibitor of the bacterial type III secretion system protects against in vivo infection with Citrobacter rodentium

Functional Genomics of Stress Response in Pseudomonas putida KT2440

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