Within-host evolution of bovine Staphylococcus aureus selects for a SigB-deficient pathotype characterized by reduced virulence but enhanced proteolytic activity and biofilm formation

MARBACH, HELENE; MAYER, KATHARINA; VOGL, CLAUS; LEE, JEAN Y. H.; MONK, IAN R.; SORDELLI, DANIEL O.; BUZZOLA, FERNANDA R.; EHLING-SCHULZ, MONIKA; GRUNERT, TOM

Scientific Reports

Nature Research

Año: 2019 vol. 9

Staphylococcus aureus is a major cause of bovine mastitis, commonly leading to long-lasting, persistentand recurrent infections. Thereby, S. aureus constantly refines and permanently adapts to the bovineudder environment. In this work, we followed S. aureus within-host adaptation over the course of threemonths in a naturally infected dairy cattle with chronic, subclinical mastitis. Whole genome sequenceanalysis revealed a complete replacement of the initial predominant variant by another isogenic variant.We report for the first time within-host evolution towards a sigma factor SigB-deficient pathotype in S.aureus bovine mastitis, associated with a single nucleotide polymorphism in rsbU (G368A → G122D), acontributor to SigB-functionality. The emerged SigB-deficient pathotype exhibits a substantial shift tonew phenotypic traits comprising strong proteolytic activity and poly-N-acetylglucosamine (PNAG)-based biofilm production. This possibly unlocks new nutritional resources and promotes immuneevasion, presumably facilitating extracellular persistence within the host. Moreover, we observed anadaptation towards attenuated virulence using a mouse infection model. This study extends the role ofsigma factor SigB in S. aureus pathogenesis, so far described to be required for intracellular persistenceduring chronic infections. Our findings suggest that S. aureus SigB-deficiency is an alternativemechanism for persistence and underpin the clinical relevance of staphylococcal SigB-deficient variantswhich are consistently isolated during human chronic infections.