In:
mSphere, American Society for Microbiology, Vol. 7, No. 3 ( 2022-06-29)
Kurzfassung:
Shigella is an Escherichia coli pathovar that colonizes the cytosol of mucosal cells in the human large intestine. To do this, Shigella uses a Type III Secretion Apparatus (T3SA) to translocate several proteins into host cells. The T3SA and its substrates are encoded by genes of the virulence plasmid pINV or by chromosomal genes derived thereof. We recently discovered two chromosomal genes, which seem unrelated to pINV, although they are activated by MxiE and IpgC similarly to some of the canonical substrates of the T3SA. Here, we showed that the production of the corresponding proteins depended on the conservation of a MxiE box in their cognate promoters. Furthermore, both proteins were secreted by the T3SA in a chaperone-independent manner through the recognition of their respective amino-terminal secretion signal. Based on these observations, we named these new genes icaR and icaT , which stand for invasion chromosome antigen with homology for a transcriptional regulator and a transposase, respectively. icaR and icaT have orthologs in commensal and pathogenic E. coli strains belonging mainly to phylogroups A, B1, D and E. Finally, we demonstrated that icaR and icaT orthologs could be activated by the coproduction of IpgC and MxiE in strains MG1655 K-12 (phylogroup A) and O157:H7 ATCC 43888 (phylogroup E). In contrast, the coproduction of EivF and YgeG, which are homologs of MxiE and IpgC in the E. coli T3SS 2 (ETT2), failed to activate icaR and icaT . IMPORTANCE icaR and icaT are the latest members of the MxiE regulon discovered in the chromosome. The proteins IcaR and IcaT, albeit produced in small amounts, are nonetheless secreted by the T3SA comparably to canonical substrates. The high occurrence of icaR and icaT in phylogroups A, B1, D, and E coupled with their widespread absence in their B2 counterparts agree with the consensus E. coli phylogeny. The widespread conservation of the MxiE box among icaR and icaT orthologs supports the notion that both genes had already undergone coevolution with transcriptional activators ipgC and mxiE - harbored in pINV or a relative- in the last common ancestor of Shigella and of E. coli from phylogroups A, B1, D, and E. The possibility that icaR and icaT may contribute to Shigella pathogenesis cannot be excluded, although some of their characteristics suggest they are fossil genes.
Materialart:
Online-Ressource
ISSN:
2379-5042
DOI:
10.1128/msphere.00115-22
Sprache:
Englisch
Verlag:
American Society for Microbiology
Publikationsdatum:
2022
ZDB Id:
2844248-9
