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Within-host evolution of bovine Staphylococcus aureus selects for a SigB-deficient pathotype characterized by reduced virulence but enhanced proteolytic activity and biofilm formation
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Within-host evolution of bovine Staphylococcus aureus selects for a SigB-deficient pathotype characterized by reduced virulence but enhanced proteolytic activity and biofilm formation
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Journal Article
Within-host evolution of bovine Staphylococcus aureus selects for a SigB-deficient pathotype characterized by reduced virulence but enhanced proteolytic activity and biofilm formation
2019
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 45/90
/ 64/60
/ 82/29
/ 82/58
/ Animals
/ Biofilms
/ Biofilms - growth & development
/ Cattle
/ Female
/ Genomes
/ Humanities and Social Sciences
/ Mastitis
/ Mastitis, Bovine - microbiology
/ Science
/ Single-nucleotide polymorphism
/ Staphylococcal Infections - veterinary
/ Staphylococcus aureus - genetics
/ Staphylococcus aureus - growth & development
/ Staphylococcus aureus - pathogenicity
/ Udder
