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The TIR Homologue Lies near Resistance Genes in Staphylococcus aureus, Coupling Modulation of Virulence and Antimicrobial Susceptibility

Patot, Sabine
Imbert, Paul
Baude, Jessica
Martins Simões, Patricia
Campergue, Jean-Baptiste
Louche, Arthur
Nijland, Reindert
Bès, Michèle
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Published in PLOS Pathogens. 2017, vol. 13, no. 1, p. e1006092
Abstract Toll/interleukin-1 receptor (TIR) domains in Toll-like receptors are essential for initiating and propagating the eukaryotic innate immune signaling cascade. Here, we investigate TirS, a Staphylococcus aureus TIR mimic that is part of a novel bacterial invasion mechanism. Its ectopic expression in eukaryotic cells inhibited TLR signaling, downregulating the NF-kB pathway through inhibition of TLR2, TLR4, TLR5, and TLR9. Skin lesions induced by the S. aureus knockout tirS mutant increased in a mouse model compared with wild-type and restored strains even though the tirS-mutant and wild-type strains did not differ in bacterial load. TirS also was associated with lower neutrophil and macrophage activity, confirming a central role in virulence attenuation through local inflammatory responses. TirS invariably localizes within the staphylococcal chromosomal cassettes (SCC) containing the fusC gene for fusidic acid resistance but not always carrying the mecA gene. Of note, sub-inhibitory concentration of fusidic acid increased tirS expression. Epidemiological studies identified no link between this effector and clinical presentation but showed a selective advantage with a SCCmec element with SCC fusC/tirS. Thus, two key traits determining the success and spread of bacterial infections are linked.
Keywords AnimalsBacterial Proteins/genetics/immunologyCell LineDisease Models, AnimalFusidic Acid/pharmacologyHEK293 CellsHumansMacrophages/immunologyMembrane Glycoproteins/genetics/immunologyMiceMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88/deficiency/geneticsNeutrophils/immunologyPenicillin-Binding Proteins/geneticsReceptors, Interleukin-1/genetics/immunologySignal Transduction/immunologyStaphylococcal Skin Infections/drug therapy/microbiologyStaphylococcus aureus/genetics/immunology/pathogenicityToll-Like Receptors/geneticsVirulence Factors/genetics/immunology
PMID: 28060920
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Article (Published version) (3.3 MB) - public document Free access
Research group Analyse génomique et fonctionnelle du staphylocoque doré (604)
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PATOT, Sabine et al. The TIR Homologue Lies near Resistance Genes in Staphylococcus aureus, Coupling Modulation of Virulence and Antimicrobial Susceptibility. In: PLOS Pathogens, 2017, vol. 13, n° 1, p. e1006092. doi: 10.1371/journal.ppat.1006092 https://archive-ouverte.unige.ch/unige:98978

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Deposited on : 2017-11-15

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