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A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains

Shambat, Srikanth Mairpady and Siemens, Nikolai and Monk, Ian R and Mohan, Disha B and Mukundan, Santhosh and Krishnan, Karthickeyan Chella and Prabhakara, Sushma and Snall, Johanna and Kearns, Angela and Vandenesch, Francois and Svensson, Mattias and Kotb, Malak and Gopal, Balasubramanian and Arakere, Gayathri and Norrby-Teglund, Anna (2016) A point mutation in AgrC determines cytotoxic or colonizing properties associated with phenotypic variants of ST22 MRSA strains. In: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND .

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Official URL: http://dx.doi.org/10.1038/srep31360

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and soft tissue infections. One of the highly successful and rapidly disseminating clones is MRSA ST22 commonly associated with skin tropism. Here we show that a naturally occurring single amino acid substitution (tyrosine to cysteine) at position 223 of AgrC determines starkly different ST22 S. aureus virulence phenotypes, e.g. cytotoxic or colonizing, as evident in both in vitro and in vivo skin infections. Y223C amino acid substitution destabilizes AgrC-AgrA interaction leading to a colonizing phenotype characterized by upregulation of bacterial surface proteins. The colonizing phenotype strains cause less severe skin tissue damage, show decreased susceptibility towards the antimicrobial LL-37 and induce autophagy. In contrast, cytotoxic strains with tyrosine at position 223 of AgrC cause infections characterized by inflammasome activation and severe skin tissue pathology. Taken together, the study demonstrates how a single amino acid substitution in the histidine kinase receptor AgrC of ST22 strains determines virulence properties and infection outcome.

Item Type: Journal Article
Publication: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Additional Information: Copy right for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 02 Nov 2016 10:05
Last Modified: 17 Oct 2018 09:41
URI: http://eprints.iisc.ac.in/id/eprint/54647

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