Genome-wide analysis of fitness determinants of Staphylococcus aureus during growth in milk.
Details
Serval ID
serval:BIB_8016DCC10E53
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide analysis of fitness determinants of Staphylococcus aureus during growth in milk.
Journal
PLoS pathogens
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Publication state
Published
Issued date
04/2025
Peer-reviewed
Oui
Volume
21
Number
4
Pages
e1013080
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
Staphylococcus aureus is a major concern in the dairy industry due to its significance as a pathogen causing bovine mastitis as well as a source of food poisoning. The nutrient-rich milk environment supports bacterial growth, but the specific genetic determinants that facilitate S. aureus proliferation and persistence in milk are poorly understood. In this study, we conducted a genome-wide CRISPR interference sequencing (CRISPRi-seq) screen with the laboratory strain S. aureus NCTC8325-4, to identify fitness determinants essential for S. aureus growth and survival in milk. We identified 282 milk-essential genes, including those with key roles in DNA replication, protein synthesis, and metabolism. Comparative analysis with brain heart infusion (BHI) as growth medium, revealed 79 genes with differential fitness, highlighting specific adaptations required for growth in milk. Notably, we found that purine biosynthesis, folate cycle pathways, and metal acquisition were particularly important in this environment. Based on this, we further demonstrate that S. aureus is more sensitive to the folate inhibitors trimethoprim-sulfamethoxazole (TMP-SMX) in milk and identify several genes whose knockdown results in hypersensitivity to TMP-SMX in milk. Additionally, our analysis showed a relatively reduced importance of cell wall components, such as teichoic acids, for S. aureus fitness in milk, which is also reflected in reduced efficiency of antimicrobials targeting teichoic acids. Together, these findings provide new insights into the genetic basis of S. aureus fitness and antibiotic susceptibility in milk, offering directions for novel treatment strategies against bovine mastitis.
Keywords
Animals, Staphylococcus aureus/genetics, Staphylococcus aureus/growth & development, Staphylococcus aureus/drug effects, Milk/microbiology, Cattle, Staphylococcal Infections/microbiology, Female, Genome-Wide Association Study, Genome, Bacterial, Mastitis, Bovine/microbiology, Anti-Bacterial Agents/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
16/04/2025 14:55
Last modification date
15/07/2025 7:15