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

• Published in: Scientific reports Vol. 9; no. 1; pp. 13479 - 12
• Main Authors: Marbach, Helene, Mayer, Katharina, Vogl, Claus, Lee, Jean Y. H., Monk, Ian R., Sordelli, Daniel O., Buzzola, Fernanda R., Ehling-Schulz, Monika, Grunert, Tom
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.09.2019; Nature Publishing Group
• Subjects: 45/23; 45/90; 631/326/107; 631/326/421; 64/60; 692/699/255/1318; 82/29; 82/58; Adaptation, Biological; Animals; Bacterial Proteins; Biofilms; Biofilms - growth & development; Cattle; Dairy cattle; Evolution, Molecular; Female; Genomes; Hemolysis; Host-Pathogen Interactions; Humanities and Social Sciences; Mastitis; Mastitis, Bovine - microbiology; multidisciplinary; N-Acetylglucosamine; Nucleotide sequence; Pathogens; Phenotype; Proteolysis; Science; Science (multidisciplinary); Sigma factor; Sigma Factor - deficiency; Single-nucleotide polymorphism; Staphylococcal Infections - veterinary; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - growth & development; Staphylococcus aureus - pathogenicity; Staphylococcus infections; Udder; Virulence
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-49981-6

Staphylococcus aureus is a major cause of bovine mastitis, commonly leading to long-lasting, persistent and recurrent infections. Thereby, S . aureus constantly refines and permanently adapts to the bovine udder environment. In this work, we followed S . aureus within-host adaptation over the course of three months in a naturally infected dairy cattle with chronic, subclinical mastitis. Whole genome sequence analysis 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), a contributor to SigB-functionality. The emerged SigB-deficient pathotype exhibits a substantial shift to new phenotypic traits comprising strong proteolytic activity and poly- N -acetylglucosamine (PNAG)-based biofilm production. This possibly unlocks new nutritional resources and promotes immune evasion, presumably facilitating extracellular persistence within the host. Moreover, we observed an adaptation towards attenuated virulence using a mouse infection model. This study extends the role of sigma factor SigB in S . aureus pathogenesis, so far described to be required for intracellular persistence during chronic infections. Our findings suggest that S . aureus SigB-deficiency is an alternative mechanism for persistence and underpin the clinical relevance of staphylococcal SigB-deficient variants which are consistently isolated during human chronic infections.