A regulatory cascade controls Staphylococcus aureus pathogenicity island activation

Haag, A. F. , Podkowik, M., Ibarra-Chávez, R., Gallego del Sol, F., Ram, G., Chen, J., Marina, A., Novick, R. P. and Penadés, J. R. (2021) A regulatory cascade controls Staphylococcus aureus pathogenicity island activation. Nature Microbiology, 6(10), pp. 1300-1308. (doi: 10.1038/s41564-021-00956-2) (PMID:34518655) (PMCID:PMC7611864)

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Abstract

Staphylococcal pathogenicity islands (SaPIs) are a family of closely related mobile chromosomal islands that encode and disseminate the superantigen toxins, toxic shock syndrome toxin 1 and superantigen enterotoxin B (SEB). They are regulated by master repressors, which are counteracted by helper phage–encoded proteins, thereby inducing their excision, replication, packaging and intercell transfer. SaPIs are major components of the staphylococcal mobilome, occupying five chromosomal att sites, with many strains harbouring two or more. As regulatory interactions between co-resident SaPIs could have profound effects on the spread of superantigen pathobiology, we initiated the current study to search for such interactions. Using classical genetics, we found that, with one exception, their regulatory systems do not cross-react. The exception was SaPI3, which was originally considered defective because it could not be mobilized by any known helper phage. We show here that SaPI3 has an atypical regulatory module and is induced not by a phage but by many other SaPIs, including SaPI2, SaPIbov1 and SaPIn1, each encoding a conserved protein, Sis, which counteracts the SaPI3 repressor, generating an intracellular regulatory cascade: the co-resident SaPI, when conventionally induced by a helper phage, expresses its sis gene which, in turn, induces SaPI3, enabling it to spread. Using bioinformatics analysis, we have identified more than 30 closely related coancestral SEB-encoding SaPI3 relatives occupying the same att site and controlled by a conserved regulatory module, immA–immR–str′. This module is functionally analogous but unrelated to the typical SaPI regulatory module, stl–str. As SaPIs are phage satellites, SaPI3 and its relatives are SaPI satellites.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ibarra Chavez, Mr Rodrigo and Penades, Prof Jose R and Haag, Dr Andreas
Authors: Haag, A. F., Podkowik, M., Ibarra-Chávez, R., Gallego del Sol, F., Ram, G., Chen, J., Marina, A., Novick, R. P., and Penadés, J. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Microbiology
Publisher:Nature Research
ISSN:2058-5276
ISSN (Online):2058-5276
Published Online:13 September 2021

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
170721Molecular biology of the PICIs, a novel and widespread family of mobile genetic elements involved in bacterial virulenceJose R PenadesMedical Research Council (MRC)MR/M003876/1III - Bacteriology - Dr J Penades
304055Deciphering Gram-negative phage-inducible chromosomal island strategies for spreading in natureJose R PenadesMedical Research Council (MRC)MRS00940X/1III - Bacteriology
172242Understanding a novel mechanim involving pathogenity islands in the transfer of unlinked chromosomal virulence genesJose R PenadesBiotechnology and Biological Sciences Research Council (BBSRC)BB/N002873/1Institute of Infection, Immunity & Inflammation
302971Helper and satellite pathogenicity islands: the discovery of two novel subcellular elements with a huge impact on bacterial pathogenesis and evolutionJose R PenadesBiotechnology and Biological Sciences Research Council (BBSRC)BB/S003835/1III - Bacteriology
173671Prof. R. Fitzgerald. Wellcome Trust Award 201531/Z/16/Z - Understanding bacterial host adaptation to combat infectious diseasesJose R PenadesWellcome Trust (WELLCOTR)R44516 - WT 201531/Z/16/ZInstitute of Infection, Immunity & Inflammation
172321DUT-SignalJose R PenadesEuropean Research Council (ERC)670932Institute of Infection, Immunity & Inflammation