Within-Host Adaptation of <i>Staphylococcus aureus</i> in a Bovine Mastitis Infection Is Associated with Increased Cytotoxicity

• Main Authors: Katharina Mayer, Martin Kucklick, Helene Marbach, Monika Ehling-Schulz, Susanne Engelmann, Tom Grunert
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: International Journal of Molecular Sciences
• Subjects: within-host adaptation; in-host evolution; <i>Staphylococcus aureus</i>; extracellular persistence; chronic bovine mastitis; cytotoxicity
• Online Access: https://www.mdpi.com/1422-0067/22/16/8840
• ISSN: 1661-6596; 1422-0067

Within-host adaptation is a typical feature of chronic, persistent <i>Staphylococcus aureus</i> infections. Research projects addressing adaptive changes due to bacterial in-host evolution increase our understanding of the pathogen’s strategies to survive and persist for a long time in various hosts such as human and bovine. In this study, we investigated the adaptive processes of <i>S. aureus</i> during chronic, persistent bovine mastitis using a previously isolated isogenic strain pair from a dairy cow with chronic, subclinical mastitis, in which the last variant (host-adapted, Sigma factor SigB-deficient) quickly replaced the initial, dominant variant. The strain pair was cultivated under specific in vitro infection-relevant growth-limiting conditions (iron-depleted RPMI under oxygen limitation). We used a combinatory approach of surfaceomics, molecular spectroscopic fingerprinting and in vitro phenotypic assays. Cellular cytotoxicity assays using red blood cells and bovine mammary epithelial cells (MAC-T) revealed changes towards a more cytotoxic phenotype in the host-adapted isolate with an increased alpha-hemolysin (α-toxin) secretion, suggesting an improved capacity to penetrate and disseminate the udder tissue. Our results foster the hypothesis that within-host evolved SigB-deficiency favours extracellular persistence in <i>S. aureus</i> infections. Here, we provide new insights into one possible adaptive strategy employed by <i>S. aureus</i> during chronic, bovine mastitis, and we emphasise the need to analyse genotype–phenotype associations under different infection-relevant growth conditions.