Kegg Pathway: Pathogenic Escherichia coli infection - EHEC

J Bacteriol. 2009 Nov 6;
Petty NK, Bulgin R, Crepin VF, Cerdeño-Tárraga AM, Schroeder GN, Quail MA, Lennard N, Corton C, Barron A, Clark L, Toribio AL, Parkhill J, Dougan G, Frankel G, Thomson NR

Citrobacter rodentium (formally C. freundii Biotype 4280) is a highly infectious pathogen that causes colitis and transmissible colonic hyperplasia in mice. In common with enteroPathogenic and enterhemorrhagic Escherichia coli (EPEC and EHEC respectively), C. rodentium exploits a type III secretion system (T3SS) to induce attaching and effacing (A/E) lesions that are essential for virulence. Here we report the fully annotated genome sequence of the 5.3 Mb chromosome and four plasmids harboured by C. rodentium strain ICC168. The genome sequence revealed key information about the phylogeny of C. rodentium and identified 1585 C. rodentium-specific (without orthologues in EPEC or EHEC) coding sequences, 10 prophage-like regions and 17 genomic islands, including the LEE region, which encodes a T3SS and effector proteins. Among the 29 T3SS effectors found in C. rodentium are all the core 22 effectors of EPEC strain E2348/69. In addition, we identified a novel C. rodentium effector, named EspS. C. rodentium harbours two type VI secretion systems (T6SS) (CTS1 and CTS2), while EHEC contains only one T6SS (EHS). Our analysis suggests that C. rodentium and EPEC/EHEC have converged on a common host infection strategy through access to a common pool of mobile DNA, and that C. rodentium has lost gene functions associated with a previous Pathogenic niche.

Can J Microbiol. 2009 Jun; 55(6): 672-9
Pitondo-Silva A, Minarini LA, Camargo IL, Darini AL

EnteroPathogenic Escherichia coli (EPEC) infections are a leading cause of infantile diarrhea in developing nations. Multilocus sequence typing (MLST) characterizes bacterial strains based on the sequences of internal fragments in housekeeping genes. Little is known about strains of EPEC analyzed by MLST from Brazil. In this study, a diverse collection of 29 EPEC strains isolated from patients with diarrhea, admitted to the University Hospital of Ribeirao Preto, was characterized by MLST. Strain analysis demonstrated 22 different sequence types (STs), of which almost half (48%) were new, indicating a high genotype diversity. The 22 STs were divided by eBURST into 12 clonal complexes. It was not possible to correlate typical and atypical EPEC with other strains in the MLST database. This is the first study that analyzed EPEC strains from South America that are included in the E. coli MLST database. Nine (31%) out of 29 strains are part of the CC10 clonal complex, the major clonal complex in the database, which comprises 174 strains and 86 different STs, suggesting that these strains might be the most important intestinal Pathogenic E. coli worldwide. Genetic relationships between typical and atypical EPEC, enterohemorrhagic E. coli, and enteroaggregative E. coli strains were not established by MLST.

Appl Environ Microbiol. 2009 Oct; 75(19): 6187-97
Slanec T, Fruth A, Creuzburg K, Schmidt H

In this study, 75 Shiga toxin (Stx)-producing Escherichia coli (STEC) strains originating from foods (n = 73) and drinking water (n = 2) were analyzed for their stx genotype, as well as for further chromosome-, phage-, and plasmid-encoded virulence factors. A broad spectrum of stx genes was detected. Fifty-three strains (70.7%) contained stx(2) or stx(2) variants, including stx(2d), mucus-activatable stx(2d), stx(2e), and stx(2g). Seven strains (9.3%) harbored stx(1) or stx(1c), and 15 strains (20.0%) carried both stx(2) and/or stx(2) variants and stx(1) or stx(1c). Beside stx, the most abundant accessory virulence markers in STEC food isolates were iha (57.3%), ehxA (40.0%), espP (28.0%), and subAB (25.3%). Only four strains were eae positive; three of these belonged to the serogroups O26, O103, and O157 and contained a typical enterohemorrhagic E. coli virulence spectrum. The results of this study show that a number of STEC strains that occur in foods appear to be Pathogenic for humans, based on their virulence profiles. Analysis of stx subtypes and detection of additional virulence factors in eae-negative strains may help to better assess the risk of such strains for causing human infection.

Expert Rev Anti Infect Ther. 2009 Aug; 7(6): 697-707
Palermo MS, Exeni RA, Fernández GC

The typical form of hemolytic uremic syndrome (HUS) is the major complication of Shiga toxin-producing Escherichia coli infections. HUS is a critical health problem in Argentina since it is the main cause of acute renal failure in children and the second cause of chronic renal failure, accounting for 20% of renal transplants in children and adolescents in Argentina. Despite extensive research in the field, the mainstay of treatment for patients with HUS is supportive therapy, and there are no specific therapies preventing or ameliorating the disease course. In this review, we present the current knowledge about Pathogenic mechanisms and discuss traditional and innovative therapeutic approaches, with special focus in Argentinean contribution. The hope that a better understanding of transmission dynamics and pathogenesis of this disease will produce better therapies to prevent the acute mortality and the long-term morbidity of HUS is the driving force for intensified research.

Int J Food Microbiol. 2009 Sep 15; 134(3): 196-200
Lee GY, Jang HI, Hwang IG, Rhee MS

Foodborne diseases occur worldwide, including through the consumption of contaminated meat. This study was conducted to investigate the prevalence of Escherichia coli contamination in fresh beef, poultry, and pork, and to determine whether any isolated E. coli possessed genes associated with Pathogenicity. Three thousand meat samples were collected from 2004 to 2006 and were tested for the presence of E. coli. Two hundred and seventy-three E. coli isolates were obtained from beef, poultry, and pork, resulting in an overall isolation rate of 9.1%. Of these isolates, 201 were obtained from 1350 pork samples (14.9%), followed by 41 of 900 poultry samples (4.6%) and 31 of 750 beef samples (4.1%). A total of 39 Pathogenic E. coli isolates from the three meat types were categorized into three virulence groups, namely enterotoxigenic E. coli (43.6%), enterohemorrhagic E. coli (EHEC) (35.9%; 22.6% of beef, 7.3% of poultry, and 2.0% of pork), and enteroPathogenic E. coli (20.5%). Fourteen strains were identified as belonging to the EHEC, which included O18, O136, O119, O86, O8, O111, O15, O128, and O6. This study demonstrated that Pathogenic E. coli are found in meat in Korea, and could act as a transmission vehicle for human infection as suggested by the occurrence and classification of Pathogenic E. coli in retail meats. Furthermore, the data from this study could be used in the risk assessment of foodborne illnesses linked to meat consumption.

Curr Protoc Microbiol. 2009 Aug; Chapter 5: Unit 5A.3
Bono JL

Escherichia coli are ubiquitous in the world, and for the most part are non-Pathogenic and part of the normal lower gastrointestinal tract in mammals. However, some Pathogenic isolates can cause severe disease that range from meningitis to hemorrhagic colitis (HC). In recent years, Shiga toxin-containing E. coli (STEC) have been a major cause of food borne and environmental cases of HC and hemolytic uremic syndrome. One STEC serotype, O157:H7, has been responsible for numerous food-associated outbreaks and recalls worldwide. The protocols in this unit will allow the reader to use real-time polymerase chain reaction genotyping to identify isolates that are more likely to cause disease in humans. The genotyping assay targets a single-nucleotide polymorphism (SNP) in the tir gene. The tir gene is located in a virulence operon called the locus for enterocyte effacement and functions as a receptor for the tight adherence of E. coli O157:H7 to epithelial cells. As more genomes are sequenced, informative SNPs that associate with phenotypes will be identified. Identifying isolates not only by their genus and species, but also by using other informative genomic traits will increase the general knowledge about their genetic diversity.

Lett Appl Microbiol. 2009 Sep; 49(3): 361-5
Looper ML, Edrington TS, Rosenkrans CF

AIM: To determine the influence of body condition (BC) and forage type on the prevalence of faecal shedding of Escherichia coli O157:H7 and Salmonella from beef cows. METHODS AND RESULTS: Thin or moderately conditioned cows (n = 115) were randomly assigned to graze either common bermudagrass (n = 3 pastures) or toxic endophyte-infected tall fescue (n = 3 pastures) for 62 days. Faecal samples were collected on day 0, 30 and 62. Overall percentage of faecal samples positive for E. coli O157:H7 was 2.6% and 2.0% for Salmonella. Percentage of cows positive for both E. coli O157:H7 and Salmonella on at least one occasion was 6.1%. BC, forage type or the interaction did not influence the prevalence of E. coli O157:H7 or Salmonella in the faeces of cows. CONCLUSIONS: BC at initiation of the grazing period or loss of BC in moderate conditioned cows during the grazing period did not influence faecal shedding of E. coli O157:H7 or Salmonella. Consumption of either forage type did not influence faecal shedding of either E. coli O157:H7 or Salmonella in beef cows of thin or moderate BC. SIGNIFICANCE AND IMPACT OF THE STUDY: Change in BC that typically occurs during the normal production cycle in grazing cows did not influence faecal shedding of Pathogenic bacteria regardless of forage type.

Zh Mikrobiol Epidemiol Immunobiol. 2009 May-Jun; 98-100
Utemuradova GE

AIM: To study etiologic structure of acute enteric infections (AEI) with isolation of hemolytic and enteroPathogenic Escherichia and to assess the efficacy of probiotic therapy during infections caused by E. coli. MATERIALS AND METHODS: Bacteriologic tests were performed in 245 children < 3 years old with acute enteric infection. Influence of colibacterin and Bifidumbacterin preparations on the dynamics of infectious process was assessed. RESULTS: Hemolytic Escherichia, enteroPathogenic E. coli, Shigella spp., and Salmonella spp. were isolated in 47.3%, 12.2%, 18.3%, and 1.8% of patients with AEI, respectively. The cause of AEI was identified in 77.1% of cases. Bifidumbacterin had good therapeutic effect on infections caused by Pathogenic E. coli including its hemolytic forms. CONCLUSION: Treatment with Bifidumbacterin improved state of the patients and resulted in suppression of growth of hemolytic Escherichia in the gut. colibacterin had a good therapeutic effect in the group of patients with domination of staphylococci, enterococci, Proteus in the gut as well as in patients with isolated Shigella and Salmonella. colibacterin is contraindicated in cases of colonization of the intestine by hemolytic E. coli.

Lett Appl Microbiol. 2009 Sep; 49(3): 403-7
Derakhshandeh A, Zahraei Salehi T, Tadjbakhsh H, Karimi V

AIMS: To identify, clone and sequence the iss (increased serum survival) gene from E. coli strain chi1378 isolated from Iranian poultry and to predict its protein product, Iss. METHODS AND RESULTS: The iss gene from E. coli strain chi1378 was amplified and cloned into the pTZ57R/T vector and sequenced. From the DNA sequence, the Iss predictive protein was evaluated using bioinformatics. Iss from strain chi1378 had 100% identity with other E. coli serotypes and isolates from different origins and also 98% identity with E. coli O157:H7 Iss protein. Phylogenetic analysis showed no significant different phylogenic groups among E. coli strains. CONCLUSIONS: The strong association of predicted Iss protein among different E. coli strains suggests that it could be a good antigen to control and detect avian Pathogenic E. coli (APEC). SIGNIFICANCE AND IMPACT OF THE STUDY: Because the exact pathogenesis and the role of virulence factors are unknown, the Iss protein could be used as a target for vaccination in the future, but further research is required.

Infect Immun. 2009 Sep; 77(9): 3639-50
Borenshtein D, Schlieper KA, Rickman BH, Chapman JM, Schweinfest CW, Fox JG, Schauer DB

Citrobacter rodentium causes epithelial hyperplasia and colitis and is used as a model for enteroPathogenic and enterohemorrhagic Escherichia coli infections. Little or no mortality develops in most inbred strains of mice, but C3H and FVB/N mice exhibit fatal outcomes of infection. Here we test the hypothesis that decreased intestinal transport activity during C. rodentium infection results in fatality in C3H/HeOu and FVB/N mice. Susceptible strains were compared to resistant C57BL/6 mice and to inbred strains SWR and SJL of Swiss origin, which have not been previously characterized for outcomes of C. rodentium infection. Mortality in susceptible strains C3H/HeOu and FVB/N was associated with significant fluid loss in feces, a remarkable downregulation of Slc26a3 and carbonic anhydrase IV (CAIV) message and protein expression, retention of chloride in stool, and hypochloremia, suggesting defects in intestinal chloride absorption. SWR, SJL, and C57BL/6 mice were resistant and survived the infection. Fluid therapy fully prevented mortality in C3H/HeOu and FVB/N mice without affecting clinical disease. Common Pathogenic mechanisms, such as decreased levels of expression of Slc26a3 and CAIV, affect intestinal ion transport in C. rodentium-infected FVB and C3H mice, resulting in profound electrolyte loss, dehydration, and mortality. Intestinal chloride absorption pathways are likely a potential target for the treatment of infectious diarrhea.

J Clin Microbiol. 2009 Aug; 47(8): 2442-51
Torres AG, Blanco M, Valenzuela P, Slater TM, Patel SD, Dahbi G, López C, Barriga XF, Blanco JE, Gomes TA, Vidal R, Blanco J

Lpf (stands for long polar fimbriae) is one of the few adhesive factors of enterohemorrhagic Escherichia coli O157:H7 associated with colonization of the intestine. E. coli O157:H7 strains possess two lpf loci encoding highly regulated fimbrial structures. Database analysis of the genes encoding the major fimbrial subunits demonstrated that they are present in commensal as well as Pathogenic (both intestinal and extraintestinal) E. coli strains and in Salmonella strains and that the lpfA1 and lpfA2 genes are highly prevalent among LEE (locus of enterocyte effacement)-positive E. coli strains associated with severe and/or epidemic disease. Further DNA sequence analysis of the lpfA1 and lpfA2 genes from different attaching-and-effacing E. coli strains has led us to the identification of several polymorphisms and the classification of the major fimbrial subunits into distinct variants. Using collections of Pathogenic E. coli isolates from Europe and Latin America, we demonstrated that the different lpfA types are associated with the presence of specific intimin (eae) adhesin variants and, most importantly, that they are found in specific E. coli pathotypes. Our results showed that the use of these fimbrial genes as markers, in combination with the different intimin types, resulted in a specific test for the identification of E. coli O157:H7, distinguishing it from other Pathogenic E. coli strains.

Cell Cycle. 2009 Jun 15; 8(12): 1935-9
Koturbash I, Thomas JE, Kovalchuk O, Kovalchuk I

Bacterial infection has been associated with several malignancies, yet the exact mechanism of infection-associated carcinogenesis remains obscure. Furthermore, it is still not clear whether oncontransformation requires an active infection process, or merely the presence of inactivated bacteria remnants is enough to cause deleterious effects. Here, we analyzed whether or not consumption of non-Pathogenic and Pathogenic heat-killed Escherichia coli leads to changes in genome stability in somatic tissues of exposed animals. For one week, mice were given to drink filtered or not-filtered water contaminated with heat-killed non-Pathogenic E. coli DH5alpha or heat-killed Pathogenic E. coli O157:H7 Sakai. Control animals received tap water. One week after exposure, molecular changes were analyzed in the small intestine, an organ that is in immediate contact with contaminated water. Additionally, we studied the effect in the distant spleen and liver, the organs that are involved in an immune response and detoxification, respectively. Finally, muscles were chosen as neutral tissues that were not supposed to be affected. Intestinal, liver and spleen but not muscle cells responded to all bacterial treatments with an increased level of DNA damage monitored by the induction of gammaH2AX foci. In the intestine, elevated levels of DNA damage were in parallel with an increase in Ku70 and p53 expression. We have also found an elevated level of cellular proliferation in the intestine, liver and spleen but not in muscle tissues of all exposed animals as measured by increase in PCNA levels. Our data suggest that exposure to heat-killed filtered bacteria can trigger substantial molecular responses and cause genomic instability in target and distant organs. Even though bacteria were non-Pathogenic and unable to cause infection, their remnants still caused a profound effect on exposed animals.

Proc Natl Acad Sci U S A. 2009 May 26; 106(21): 8713-8
Leopold SR, Magrini V, Holt NJ, Shaikh N, Mardis ER, Cagno J, Ogura Y, Iguchi A, Hayashi T, Mellmann A, Karch H, Besser TE, Sawyer SA, Whittam TS, Tarr PI

Single nucleotide polymorphisms (SNPs) in stable genome regions provide durable measurements of species evolution. We systematically identified each SNP in concatenations of all backbone ORFs in 7 newly or previously sequenced evolutionarily instructive Pathogenic Escherichia coli O157:H7, O157:H(-), and O55:H7. The 1,113 synonymous SNPs demonstrate emergence of the largest cluster of this pathogen only in the last millennium. Unexpectedly, shared SNPs within circumscribed clusters of organisms suggest severely restricted survival and limited effective population sizes of Pathogenic O157:H7, tenuous survival of these organisms in nature, source-sink evolutionary dynamics, or, possibly, a limited number of mutations that confer selective advantage. A single large segment spanning the rfb-gnd gene cluster is the only backbone region convincingly acquired by recombination as O157 emerged from O55. This concatenomic analysis also supports using SNPs to differentiate closely related pathogens for infection control and forensic purposes. However, constrained radiations raise the possibility of making false associations between isolates.

J Clin Microbiol. 2009 Jul; 47(7): 2061-6
Bielaszewska M, Stoewe F, Fruth A, Zhang W, Prager R, Brockmeyer J, Mellmann A, Karch H, Friedrich AW

Shiga toxin (Stx)-producing Escherichia coli (STEC) strains of serogroup O91 are the most common human Pathogenic eae-negative STEC strains. To facilitate diagnosis and subtyping of these pathogens, we genotypically and phenotypically characterized 100 clinical STEC O91 isolates. Motile strains expressed flagellar antigens H8 (1 strain), H10 (2 strains), H14 (52 strains), and H21 (20 strains) or were H nontypeable (Hnt) (10 strains); 15 strains were nonmotile. All nonmotile and Hnt strains possessed the fliC gene encoding the flagellin subunit of the H14 antigen (fliC(H14)). Most STEC O91 strains possessed enterohemorrhagic E. coli hlyA and expressed an enterohemolytic phenotype. Among seven stx alleles identified, stx(2dact), encoding mucus- and elastase-activatable Stx2d, was present solely in STEC O91:H21, whereas most strains of the other serotypes possessed stx(1). Moreover, only STEC O91:H21 possessed the cdt-V cluster, encoding cytolethal distending toxin V; the toxin was regularly expressed and was lethal to human microvascular endothelial cells. infection with STEC O91:H21 was associated with hemolytic-uremic syndrome (P = 0.0015), whereas strains of the other serotypes originated mostly in patients with nonbloody diarrhea. We conclude that STEC O91 clinical isolates belong to at least four lineages that differ by H antigens/fliC types, stx genotypes, and non-stx putative virulence factors, with accumulation of virulence determinants in the O91:H21 lineage. Isolation of STEC O91 from patients' stools on enterohemolysin agar and the rapid initial subtyping of these isolates using fliC genotyping facilitate the identification of these emerging pathogens in clinical and epidemiological studies and enable prediction of the risk of a severe clinical outcome.

Acta Clin Belg. 2009 Jan-Feb; 64(1): 59-64
Buvens G, Piérard D, Hachimi-Idrissi S, Lauwers S

We report a case of haemolytic uraemic syndrome (HUS) following an infection with a sorbitol-fermenting Verocytotoxin-producing Escherichia coli (VTEC) O157:H- in a toddler living in the province of East Flanders, Belgium. The patient presented with haemolytic anaemia, haematuria, proteinuria, renal insufficiency, and thrombocytopaenia leading to the diagnosis of HUS. Risk factors for VTEC infection, such as consuming undercooked food of bovine origin and direct contact with farm animals were absent. Also, neither travelling nor contact with travellers were reported. The patient recovered after perfusion with fresh frozen plasma and blood transfusion, and dialysis was not required. This is the first isolation of a sorbitol-fermenting VTEC O157:H- in Belgium. Future research is needed to reveal epidemiologic aspects, such as the main reservoir and transmission routes of this Pathogenic E. coli serotype, which has caused outbreaks of HUS in Germany and Scotland.

Cell Host Microbe. 2009 Mar 19; 5(3): 244-58
Weiss SM, Ladwein M, Schmidt D, Ehinger J, Lommel S, Städing K, Beutling U, Disanza A, Frank R, Jänsch L, Scita G, Gunzer F, Rottner K, Stradal TE

Actin pedestal formation by Pathogenic E. coli requires signaling by the bacterial intimin receptor Tir, which induces host cell actin polymerization mediated by N-WASP and the Arp2/3 complex. Whereas canonical enteroPathogenic E. coli (EPEC) recruit these actin regulators through tyrosine kinase signaling cascades, enterohemorrhagic E. coli (EHEC) O157:H7 employ the bacterial effector EspF(U) (TccP), a potent N-WASP activator. Here, we show that IRSp53 family members, key regulators of membrane and actin dynamics, directly interact with both Tir and EspF(U). IRSp53 colocalizes with EspF(U) and N-WASP in actin pedestals. In addition, targeting of IRSp53 is independent of EspF(U) and N-WASP but requires Tir residues 454-463, previously shown to be essential for EspF(U)-dependent actin assembly. Genetic and functional loss of IRSp53 abrogates actin assembly mediated by EHEC. Collectively, these data indentify IRSp53 family proteins as the missing host cell factors linking bacterial Tir and EspF(U) in EHEC pedestal formation.

Cell Host Microbe. 2009 Mar 19; 5(3): 215-7
Yi CR, Goldberg MB

Many Pathogenic bacteria exploit host cytoskeletal pathways to promote infection. In this issue of Cell Host & Microbe, Weiss et al. (2009) identify the host factor IRSp53 as the missing link that connects two intracellular bacterial proteins, thereby completing an actin cytoskeletal signaling pathway critical to enterohemorrhagic Escherichia coli pathogenesis.

Foodborne Pathog Dis. 2009 Mar; 6(2): 257-9
Maurer C, Meunier D, Madec JY

Enrofloxacin-resistant mutants of Stx2-producing Escherichia coli O157:H7 from cattle were selected. Mutants produced threefold higher Stx2 levels than native strains after induction with enrofloxacin. Mutants were also inducible using hundredfold higher enrofloxacin concentrations than the ones used for native strains. These results suggest that Escherichia coli O157:H7 from cattle may become more frequently Pathogenic to humans as a side effect of the increasing use of veterinary fluoroquinolones.

Emerg Infect Dis. 2009 Mar; 15(3): 372-80
Newton HJ, Sloan J, Bulach DM, Seemann T, Allison CC, Tauschek M, Robins-Browne RM, Paton JC, Whittam TS, Paton AW, Hartland EL

Most Shiga toxin-producing Escherichia coli (STEC) infections that are associated with severe sequelae such as hemolytic uremic syndrome (HUS) are caused by attaching and effacing pathogens that carry the locus of enterocyte effacement (LEE). However, a proportion of STEC isolates that do not carry LEE have been associated with HUS. To clarify the emergence of LEE-negative STEC, we compared the genetic composition of the virulence plasmids pO113 and pO157 from LEE-negative and LEE-positive STEC, respectively. The complete nucleotide sequence of pO113 showed that several plasmid genes were shared by STEC O157:H7. In addition, allelic profiling of the ehxA gene demonstrated that pO113 belongs to a different evolutionary lineage than pO157 and that the virulence plasmids of LEE-negative STEC strains were highly related. In contrast, multilocus sequence typing of 17 LEE-negative STEC isolates showed several clonal groups, suggesting that Pathogenic LEE-negative STEC has emerged several times throughout its evolution.

Dtsch Med Wochenschr. 2009 Feb; 134(9): 417-20
Klapproth JM, Meyer F

INTRODUCTION: Gastrointestinal infections are a significant cause of diarrhea and a worldwide problem with annually one billion illnesses and 3 to 4 million deaths. Gram negative bacteria like EnteroPathogenic E. coli (EPEC) in developing countries and Enterohemorrhagic E. coli (EHEC) in the developed world are responsible for the majority of acute diarrheal episodes, especially among children less than three years of age. Pathogenic E. coli are supplied with an arsenal of effector proteins to modify and neutralize specific cellular functions of the host organism. METHODS: Based on personal and extensively published results we provide a selected overview of Gram negative virulence functions with a focus on lymphostatin. RESULTS: Lymphostatin is an effector protein encoded by lifA/efa-1 (lymphocyte inhibitory factor A/ EHEC factor for adherence). lifA/efa-1 and homologous genes have been identified in EPEC, EHEC, and mouse pathogen Citrobacter rodentium, as well as various Chlamydia strains. Multiple groups have shown that in various EHEC strains lifA/efa-1 is part of a larger Pathogenicity island responsible for increased virulence. Statistically, DNA Microarray analysis associated lifA/efa-1 as the single most imortant gene with diarrhea caused by EPEC. Interestingly, lifA/efa-1 encodes for two critical enzymatic activities that have been identified in other Pathogenic bacteria: glucosyltransferase- in Clostridium- and protease activity in Yersinia strains. In vitro studies identified lymphostatin as an effector protein with an immunosuppressive effect on peripheral blood and gastrointestinal mucosa T lymphocytes. Further, lymphostatin regulates the barrier function of epithelial monolayer cultures: activation of small GTPase RhoA and inhibition of Cdc42 lead to disassembly of adherens junctions and tight junctions, respectively. Besides an effect on immune and epithelial barrier function, lymphostatin also functions as an adhesion factor for EPEC and EHEC, is essential for colonization of mouse and calf intestine, and regulates bacterial effector proteins. SUMMARY: Lymphostatin is a common toxin in Gram negative bacteria with multiple functions: cell adhesion, immunosuppression, disruption of epithelial barrier function, and intestinal colonization.