ClyA cytolysin from Salmonella: distribution within the genus, regulation of expression by SlyA, and pore-forming characteristics.
Functional homologs of the Escherichia coli cytolysin A (clyA, hlyE, sheA) gene have recently been detected in Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A). In this study, analysis of a collection of Salmonella strains showed that all S. Typhi and S. Paratyphi A strains tested harbor an intact copy of the corresponding clyA variant, i.e. clyA(STy) and clyA(SPaA), respectively. On the other hand, clyA proved to be absent in the S. enterica serovar Paratyphi B and serovar Paratyphi C strains, in various non-typhoid S. enterica subsp. enterica serovars (Typhimurium, Enteritidis, Choleraesuis, Dublin, and Gallinarum), and in S. enterica subsp. arizonae and Salmonella bongori strains. When grown under normal laboratory conditions, the S. Typhi and S. Paratyphi A strains produced only basal amounts of ClyA protein and did not exhibit a clyA-dependent hemolytic phenotype. RT-PCR and immunoblot analyses as well as phenotypic data revealed, however, that the expression of clyA(STy) and clyA(SPaA) can be activated by the Salmonella transcription factor SlyA. In addition, osmotic protection assays and lipid bilayer experiments demonstrated that the hemolytic ClyA(STy) and ClyA(SPaA) proteins are effective pore-forming toxins which, similar to E. coli ClyA, generate large, stable, moderately cation-selective channels in target membranes. Taken together with our recent serological findings which have indicated that S. Typhi and S. Paratyphi A strains produce substantial amounts of ClyA during human infection, these data suggest that ClyA may play a role in S. Typhi and S. Paratyphi A pathogenesis.
von Rhein
Christine
C
Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Bauer
Susanne
S
López Sanjurjo
Enrique Javier
EJ
Benz
Roland
R
Goebel
Werner
W
Ludwig
Albrecht
A
D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D023061:Gene Order; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D054353:Perforin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019779:Salmonella enterica / Q000235:genetics / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D037521:Virulence Factors; D054353:Perforin