Abstract
Antibiotics have been described to modulate bacterial virulence gene expression. This study aimed to assess the changes caused by anti-Staphylococcus agents in the transcription of leucocidin ED (lukED) gene of Staphylococcus aureus strain Newman in vitro and in vivo and to determine whether the altered expression is agr dependent. The bacteria were exposed to subinhibitory concentrations [1/2, 1/4, or 1/8 minimal inhibitory concentration (MIC)] of 11 antibiotics, and the expression of lukE and agr-effector RNAIII was determined using qRT-PCR. In vivo experiments were performed to evaluate the impact exerted by six representative antibiotics on the transcription of both genes. Molecular analysis showed that in vitro lukE transcription was dramatically promoted in the Newman strain exposed to sub-MICs of vancomycin, trimethoprim–sulfamethoxazole, clindamycin, gentamicin, daptomycin, and ciprofloxacin and considerably reduced when stimulated by cefazolin, erythromycin, rifampicin, tigecycline, and linezolid. In the murine abscess model, tigecycline significantly decreased the transcription of lukE and the bacterial numbers, whereas vancomycin increased them; although cefazolin increased the lukE expression (contrary to the in vitro effect), it had a remarkable role in reducing bacterial load. The correspondence analysis shows that RNAIII expression varied under seven of 11 antibiotics in vitro, and six drugs in vivo were consistent with lukE transcripts. In conclusion, our data show that anti-Staphylococcus antibiotics exert modulatory effects on lukE expression in vitro and/or in vivo, and the changed expression caused by some drugs may be involved with agr activity, thus providing a guide to choose appropriate agents to avoid promoting bacterial virulence in lukED-positive S. aureus infections.
Highlights
MATERIALS AND METHODSStaphylococcus aureus is a pathogen notorious for its ability to cause many infection-related illnesses ranging from cutaneous infections and food poisoning to toxic shock syndrome, septicemia, and necrotizing pneumonia (Tong et al, 2015)
Epidemiological data and animal infection models show that lukED can be commonly detected in clinical S. aureus strains and is closely associated with impetigo, antibiotic-associated diarrhea, and bloodstream infection, among others (Gravet et al, 1998; Arciola et al, 2007; Alonzo et al, 2012; Alonzo and Torres, 2014; He et al, 2018)
The agr operon encodes the regulatory RNA RNAIII, which promotes the transcription of leucocidin genes by negatively controlling the yield of repressor of toxin (Rot) (Benson et al, 2014; Killikelly et al, 2015; Tan et al, 2018)
Summary
MATERIALS AND METHODSStaphylococcus aureus is a pathogen notorious for its ability to cause many infection-related illnesses ranging from cutaneous infections and food poisoning to toxic shock syndrome, septicemia, and necrotizing pneumonia (Tong et al, 2015). Trimethoprim–sulfamethoxazole, clindamycin, gentamicin, or daptomycin at all sub-MICs tested significantly increased lukE expression levels than did the no-drug control.
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