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Biotope-dependent High Level Resistance to Reactive Oxygen Species, Antibiotic Tolerance, and Virulence of Staphylococcus aureus

ABSTRACT: The human and livestock pathogen Staphylococcus aureus poses a major clinical challenge due to antibiotic treatment failure. Its resilience is mainly attributed to antibiotic resistance and tolerance mechanisms related to persistence. Here we investigate how two infection-relevant conditions, milk and serum, shape S. aureus pathogenic properties and capacity to withstand environmental stresses. Milk- versus serum-grown bacteria show gross differences in envelope physical properties, membrane fatty acid composition and rigidity, and pigment production, and display distinct proteomic profiles. Compared to serum, milk adaptation of S. aureus confers extreme resistance to ROS damage, pronounced antimicrobial tolerance, and accelerated killing in a larvae infection model. High level S. aureus pigmentation in whole milk is stimulated by milk lipids, and is responsible for high ROS resistance. The remarkable robustness of S. aureus in a milk biotope may signal the need to adjust antibiotic regimens when treating mastitis infections in humans and livestock.

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ORGANISM(S): Staphylococcus Aureus

SUBMITTER: Zoran Minic

LAB HEAD: Jasmina Vidic

PROVIDER: PXD064173 | Pride | 2026-05-25

REPOSITORIES: Pride

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Project description:Staphylococci are major pathogens in humans and animals and emerging antibiotic-resistant strains have further increased the importance of this health issue. The existence of a genetic basis of host response to bacterial infections has been widely documented but the underlying mechanisms and genes are still largely unknown. Previously, two divergent lines of sheep selected on their milk somatic cell count called high and low SCS lines, have been showed to be respectively more and less susceptible to intra mammary infections (IMI). Transcriptional profiling of milk somatic cells (MSC) of high and low SCS sheep infected successively by S. epidermidis and S. aureus was performed to provide enhanced knowledge about the genetic basis of differential host response to IMI with Staphylococci. Gene expression in MSC of high and low SCS sheep collected 12h post-challenge was performed on a 15K gene ovine oligoarray (Agilent). MSC were mainly neutrophils. The high number of differentially expressed genes between the two bacterial strains indicated, among others, increased number of T-cells in MSC after S. aureus, compared to S. epidermidis challenge. Differential regulation of 366 genes between resistant and susceptible animals was largely associated with immune and inflammatory response (including pathogen recognition TLR2 pathway and cell migration), signal transduction, cell proliferation and apoptosis. Close biological connection between most of differentially expressed genes into Ingenuity Pathway Analysis networks further indicated consistency between the genes that were differentially-expressed between resistant and susceptible animals. Gene profiling in high and low SCS sheep provided strong candidates for biological pathway and gene underlying genetically determined resistance and susceptibility towards Staphylococci infections opening new fields for further investigation. Keywords: Staphylococcus epidermidis, Staphylococcus aureus, milk somatic cells, mammalian, transcriptome, immunity, mastitis 22 samples in a two-colour dye-swap experimental design

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Biotope-dependent High Level Resistance to Reactive Oxygen Species, Antibiotic Tolerance, and Virulence of Staphylococcus aureus

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