Sub-Inhibitory Concentrations of Oxacillin, but Not Clindamycin, Linezolid, or Tigecycline, Decrease Staphylococcal Phenol-Soluble Modulin Expression in Community-Acquired Methicillin-Resistant Staphylococcus aureus

• Published in: Microbiology spectrum Vol. 10; no. 1; p. e0080821
• Main Authors: Hodille, Elisabeth, Beraud, Laetitia, Périan, Séverine, Berti, Valentine, Bes, Michèle, Tristan, Anne, Blond, Emilie, Lina, Gérard, Dumitrescu, Oana
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 23.02.2022
• Subjects: Anti-Bacterial Agents - pharmacology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacterial Toxins - biosynthesis; Bacteriology; Clindamycin - pharmacology; community-acquired methicillin-resistant Staphylococcus aureus; Gene Expression Regulation, Bacterial - drug effects; Humans; Life Sciences; Linezolid - pharmacology; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - genetics; Methicillin-Resistant Staphylococcus aureus - metabolism; Microbial Sensitivity Tests; Oxacillin - pharmacology; phenol-soluble modulins alpha; Research Article; ST8 USA300 clone; ST80 European clone; Staphylococcal Infections - microbiology; Staphylococcus aureus; Tigecycline - pharmacology; virulence factors; phenol-soluble modulins alpha; community-acquired methicillin-resistant Staphylococcus aureus; ST80 European clone; ST8 USA300 clone; delta-hemolysin; modulation expression; antibiotics; subinhibitory concentration; Staphylococcus aureus; virulence factors
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.00808-21

Staphylococcus aureus (SA) is a major human pathogen producing virulence factors, such as Panton-Valentine-leucocidin (PVL), alpha-hemolysin (Hla), and phenol-soluble-modulins alpha (PSMα), including delta-hemolysin (Hld). Unlike oxacillin, clindamycin and linezolid subinhibitory concentrations (sub-MIC) display an anti-toxin effect on PVL and Hla expression. Few studies have investigated PSMα and Hld expression modulation by antibiotics. Herein, we assessed the effect of antibiotic sub-MIC on PSMα1 and Hld expression for 4 community-acquired methicillin-resistant SA (CA-MRSA), 2 strains belonging to USASA300 and 2 strains belonging to ST80 European clone. SA were grown under oxacillin, clindamycin, linezolid, or tigecycline. After incubation, culture pellets were used for the determination of , , mRNA, and levels by relative quantitative RT-PCR. PSMα1 and Hld expressions were measured in supernatant using high-performance-liquid-chromatography coupled to mass-spectrometry (HPLC-MS). Oxacillin sub-MIC reduced PSMα1 and Hld production, partially related to mRNA variations. For other antibiotics, effects on toxin expression were strain or clone dependent. Antibiotic effect on mRNA did not always reflect protein expression modulation. Variations of , mRNA, and RNAIII levels were insufficient to explain toxin expression modulation. Altogether, these data indicate that PSMα and Hld expressions are modulated by antibiotics (potential anti-toxin effect of oxacillin) differently compared to PVL and Hla. Staphylococcal toxins play an important role in the physiopathology of staphylococcal infections. Subinhibitory concentrations (sub-MIC) of antibiotics modulate toxins expression in S. aureus: clindamycin (CLI) and linezolid (LIN) display an anti-toxin effect on Panton-Valentine leucocidin and alpha-hemolysin production, while oxacillin (OXA) has an inducing effect. Few studies have focused on the modulation of phenol-soluble modulins alpha (PSMα) including delta-hemolysin expression by sub-MIC antibiotics. The aim of the present study was to investigate the effects of sub-MIC antibiotics on the expression of PSMα toxins for 4 community-acquired methicillin-resistant (CA-MRSA) clinical isolates. The data presented herein confirm that OXA sub-MICs constantly inhibit PSMα production for CA-MRSA. Certain strains of S. aureus are highly sensitive to sub-MICs of protein synthesis inhibitory agents, resulting in an important increase of mRNA levels to overcome the intrinsic ribosome blockage ability of these antibiotics, eventually translating in increased expression of toxins.