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Gene Review:

ehxA - hemolysin A

Escherichia coli

Boerlin, P. et al., Djordjevic, S.P. et al., Djordjevic, S.P. et al., Rashid, R.A. et al., Gilbert, R.A. et al., et al.

Djordjevic, Ramachandran, Bettelheim, Vanselow, Holst, Bailey, Hornitzky, Rey, Sánchez, Blanco, Hermoso de Mendoza, Hermoso de Mendoza, García, Gil, Tejero, Rubio, Alonso, Djordjevic, Hornitzky, Bailey, Gill, Vanselow, Walker, Bettelheim, Feng, Weagant, Monday, Liptakova, Siegfried, Rosocha, Podracka, Bogyiova, Kotulova, Gilbert, Tomkins, Padmanabha, Gough, Krause, McSweeney, Scott, McGee, Minihan, Sheridan, Earley, Leonard,

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Disease relevance of ehxA

All E. coli O157:H7 isolates obtained were examined by pulsed field gel electrophoresis (PFGE), polymerase chain reaction (PCR) to detect eaeA, ehxA, stx1 and stx2 genes and antibiotic sensitivity profiling [1].
Shiga toxin-producing Escherichia coli (STEC) strains possessing genes for enterohemolysin (ehxA) and/or intimin (eae), referred to here as complex STEC (cSTEC), are more commonly recovered from the feces of humans with hemolytic uremic syndrome and hemorrhagic colitis than STEC strains that do not possess these accessory virulence genes [2].
We show that the C-terminal 70 amino acids of leukotoxin from Pasteurella hemolytica can substitute functionally for the HlyA signal sequence [3].

High impact information on ehxA

We examined these genes in fecal samples from eight humans and four calves. iha and espA were significantly more expressed in bovine infections. rfbE and ehxA appeared to be more highly expressed in human infections, though these differences did not achieve statistical significance [4].
This study assessed the diversity of the enterohemorrhagic Escherichia coli (EHEC) hemolysin gene (ehxA) in a variety of Shiga toxin-producing E. coli (STEC) serotypes and the relationship between ehxA types and virulence markers on the locus for enterocyte effacement (LEE) [5].
Phylogenetic analysis of a subset of 27 STEC isolates, one enteropathogenic E. coli isolate, and a K-12 reference isolate showed that eae-positive STEC isolates all belong to a single evolutionary lineage and that the EHEC hemolysin plasmid and the ehxA gene evolved within this lineage without recent horizontal transfer [5].
Restriction fragment length polymorphism of the ehxA gene and flanking sequences and of the E. coli attaching and effacing (eae) gene was determined for 79 EHEC hemolysin-positive STEC isolates of 37 serotypes [5].
Digestion of an ehxA PCR product with the restriction endonuclease TaqI showed a unique restriction pattern for eae-negative isolates and another one for isolates of serotypes O157:H7 and O157:NM [5].

Chemical compound and disease context of ehxA

Increased E. coli numbers, decreased pH and enhanced butyrate and lactate fermentation pathways were associated with grain diets, whereas roughage and roughage + molasses diets resulted in decreased concentrations of ehxA, eaeA and stx(1) genes, this trend remaining at lairage [6].
Fourteen sorbitol-non-fermenting E. coli O157 isolates harbouring the vtx2, eae and ehxA genes were obtained [7].

Biological context of ehxA

Isolates obtained from the patient and the garden plots during this investigation had indistinguishable PFGE patterns and had the same virulence factors (stx1, stx2, eaeA, ehxA) [8].
Comparisons of the ehxA gene sequences of representative isolates of each group showed that this gene and the rest of the EHEC hemolysin operon are highly conserved [5].
Sequences homologous to ehxA were found in 102 (46%) of the 220 strains [9].
Comparison of the sequences showed that the upstream primer binding site in the ehxA gene of O104:H21 was not identical to that of O157:H7 [10].

Anatomical context of ehxA

A total of 78 of 90 STEC isolates (86.7%) expressed Shiga toxin in Vero cell culture and 75 of 84 ehxA-positive isolates (89.3%) expressed enterohemolysin on washed sheep blood agar. eaeA was observed in 11 of 90 (12.2%) ovine STEC isolates, including serotypes O5:H(-), O84:H(-), O85:H49, O123:H(-) O136:H40, and O157:H(-) [11].
Bacterial hemolysins and leukotoxins affect target cells by forming large exogenous pores into their plasma membrane: Escherichia coli hemolysin A as a case example [12].

Associations of ehxA with chemical compounds

Whereas all STEC caprine isolates showed ehxA genes, only O157:H7 serotype showed eae virulence genes [13].

Other interactions of ehxA

Eighty-two percent of the strains showed further putative virulence factors: 13% were eae-, 60% ehxA- and 67% saa-positive [14].

Analytical, diagnostic and therapeutic context of ehxA

Secretion and circular dichroism analysis of the C-terminal signal peptides of HlyA and LktA [15].

References

The characterisation of E. coli O157:H7 isolates from cattle faeces and feedlot environment using PFGE. Scott, L., McGee, P., Minihan, D., Sheridan, J.J., Earley, B., Leonard, N. Vet. Microbiol. (2006) [Pubmed]
Serotypes and virulence gene profiles of shiga toxin-producing Escherichia coli strains isolated from feces of pasture-fed and lot-fed sheep. Djordjevic, S.P., Ramachandran, V., Bettelheim, K.A., Vanselow, B.A., Holst, P., Bailey, G., Hornitzky, M.A. Appl. Environ. Microbiol. (2004) [Pubmed]
Functional replacement of the hemolysin A transport signal by a different primary sequence. Zhang, F., Greig, D.I., Ling, V. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
Expression of putative virulence factors of Escherichia coli O157:H7 differs in bovine and human infections. Rashid, R.A., Tabata, T.A., Oatley, M.J., Besser, T.E., Tarr, P.I., Moseley, S.L. Infect. Immun. (2006) [Pubmed]
Evolution of enterohemorrhagic Escherichia coli hemolysin plasmids and the locus for enterocyte effacement in shiga toxin-producing E. coli. Boerlin, P., Chen, S., Colbourne, J.K., Johnson, R., De Grandis, S., Gyles, C. Infect. Immun. (1998) [Pubmed]
Effect of finishing diets on Escherichia coli populations and prevalence of enterohaemorrhagic E. coli virulence genes in cattle faeces. Gilbert, R.A., Tomkins, N., Padmanabha, J., Gough, J.M., Krause, D.O., McSweeney, C.S. J. Appl. Microbiol. (2005) [Pubmed]
A family outbreak of haemolytic uraemic syndrome and haemorrhagic colitis caused by verocytotoxigenic Escherichia coli O157 from unpasteurised cow's milk in Slovakia. Liptakova, A., Siegfried, L., Rosocha, J., Podracka, L., Bogyiova, E., Kotulova, D. Clin. Microbiol. Infect. (2004) [Pubmed]
Soil survival of Escherichia coli O157:H7 acquired by a child from garden soil recently fertilized with cattle manure. Mukherjee, A., Cho, S., Scheftel, J., Jawahir, S., Smith, K., Diez-Gonzalez, F. J. Appl. Microbiol. (2006) [Pubmed]
Prevalence and characterization of Shiga toxin-producing Escherichia coli isolated from cattle, food, and children during a one-year prospective study in France. Pradel, N., Livrelli, V., De Champs, C., Palcoux, J.B., Reynaud, A., Scheutz, F., Sirot, J., Joly, B., Forestier, C. J. Clin. Microbiol. (2000) [Pubmed]
Genetic analysis for virulence factors in Escherichia coli O104:H21 that was implicated in an outbreak of hemorrhagic colitis. Feng, P., Weagant, S.D., Monday, S.R. J. Clin. Microbiol. (2001) [Pubmed]
Virulence properties and serotypes of Shiga toxin-producing Escherichia coli from healthy Australian slaughter-age sheep. Djordjevic, S.P., Hornitzky, M.A., Bailey, G., Gill, P., Vanselow, B., Walker, K., Bettelheim, K.A. J. Clin. Microbiol. (2001) [Pubmed]
Bacterial hemolysins and leukotoxins affect target cells by forming large exogenous pores into their plasma membrane: Escherichia coli hemolysin A as a case example. Menestrina, G., Dalla Serra, M., Pederzolli, C., Bregante, M., Gambale, F. Biosci. Rep. (1995) [Pubmed]
Prevalence, serotypes and virulence genes of Shiga toxin-producing Escherichia coli isolated from ovine and caprine milk and other dairy products in Spain. Rey, J., Sánchez, S., Blanco, J.E., Hermoso de Mendoza, J., Hermoso de Mendoza, M., García, A., Gil, C., Tejero, N., Rubio, R., Alonso, J.M. Int. J. Food Microbiol. (2006) [Pubmed]
Serotypes and virulence genes of ovine non-O157 Shiga toxin-producing Escherichia coli in Switzerland. Zweifel, C., Blanco, J.E., Blanco, M., Blanco, J., Stephan, R. Int. J. Food Microbiol. (2004) [Pubmed]
Secretion and circular dichroism analysis of the C-terminal signal peptides of HlyA and LktA. Zhang, F., Yin, Y., Arrowsmith, C.H., Ling, V. Biochemistry (1995) [Pubmed]

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