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

• DOI: 10.1038/srep31360
• Publication Date: 2016-08-11T10:59:10Z
• Authors: Srikanth Mairpady...; Nikolai Siemens; Ian R. Monk; Disha B. Mohan; Santhosh Mukundan; Karthickeyan Chel...; Sushma Prabhakara; Johanna Snäll; Angela Kearns; Francois Vandenesch; Mattias Svensson; Malak Kotb; Balasubramanian G...; Gayathri Arakere; Anna Norrby-Teglund
• Keywords: Methicillin-Resistant Staphylococcus aureus; 0301 basic medicine; 570; [SDV.IMM] Life Sciences [q-bio]/Immunology; 610; Molecular Biophysics Unit; Article; Cell Line; Mice; 03 medical and health sciences; Bacterial Proteins; Cathelicidins; Animals; Humans; Point Mutation; Cysteine; [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology; 0303 health sciences; Animal; [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology; 3. Good health; Disease Models, Animal; Viral Tropism; Phenotype; Amino Acid Substitution; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; Disease Models; [SDV.IMM]Life Sciences [q-bio]/Immunology; Tyrosine; Staphylococcal Skin Infections; [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology; Protein Kinases; Antimicrobial Cationic Peptides; Protein Binding

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