Antibiotic-mediated selection of quorum-sensing-negative Staphylococcus aureus

TY - JOUR

T1 - Antibiotic-mediated selection of quorum-sensing-negative Staphylococcus aureus

AU - Paulander, Wilhelm Erik Axel

AU - Varming, Anders Nissen

AU - Bæk, Kristoffer Torbjørn

AU - Haaber, Jakob Krause

AU - Frees, Dorte

AU - Ingmer, Hanne

N1 - e00459-12

PY - 2012

Y1 - 2012

N2 - Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing lifethreatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene expression. We demonstrate that the presence of the agr locus imposes a fitness cost on S. aureus that is mediated by the expression of RNAIII. Further, we show that exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and rifampin, each targeting separate cellular functions, markedly increases the agrmediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among communityacquired S. aureus strains. Importantly, agr deficiency correlates with increased duration of and mortality due to bacteremia during antibiotic treatment and with a higher frequency of glycopeptide resistance than in agr-carrying strains. Our results provide an explanation for the frequent isolation of agr-defective strains from hospital-acquired S. aureus infections and suggest that the adaptability of S. aureus to antibiotics involves the agr locus.

AB - Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing lifethreatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene expression. We demonstrate that the presence of the agr locus imposes a fitness cost on S. aureus that is mediated by the expression of RNAIII. Further, we show that exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and rifampin, each targeting separate cellular functions, markedly increases the agrmediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among communityacquired S. aureus strains. Importantly, agr deficiency correlates with increased duration of and mortality due to bacteremia during antibiotic treatment and with a higher frequency of glycopeptide resistance than in agr-carrying strains. Our results provide an explanation for the frequent isolation of agr-defective strains from hospital-acquired S. aureus infections and suggest that the adaptability of S. aureus to antibiotics involves the agr locus.

U2 - 10.1128/mBio.00459-12

DO - 10.1128/mBio.00459-12

M3 - Journal article

C2 - 23143800

SN - 2161-2129

VL - 3

SP - e00459-12

JO - mBio

JF - mBio

IS - 6

ER -