Potential antivirulence and antibiofilm activities of sub-MIC of oxacillin against MDR S. aureus isolates: an in-vitro and in-vivo study

• Published in: BMC microbiology 2024-08, Vol.24 (1), p.295-18, Article 295
• Main Authors: Omar, Amira, El-Banna, Tarek E, Sonbol, Fatma I, El-Bouseary, Maisra M
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Antimicrobial agents; Bacteria; Biocompatibility; Biofilm; Biofilms; Biofilms - drug effects; Care and treatment; Coagulase; Confocal microscopy; Diagnosis; Disease Models, Animal; Drug resistance; Drug resistance in microorganisms; Drug Resistance, Multiple, Bacterial - drug effects; Electron microscopy; Gene expression; Gentian violet; Humans; Investigations; Laboratory animals; Mice; Microbial Sensitivity Tests; Minimum inhibitory concentration; Morbidity; Multidrug resistance; Nosocomial infection; Oxacillin; Oxacillin - pharmacology; Phenols; Polymerase chain reaction; Prevention; Reverse transcription; Risk factors; S. aureus; Scanning microscopy; Septic shock; Staphylococcal enterotoxin F; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - physiology; Staphylococcus aureus infections; Staphylococcus infections; Sub-MIC; Sulfuric acid; Toxic shock syndrome; Toxins; Transcription factors; Virulence; Virulence (Microbiology); Virulence - drug effects; Virulence factors; Virulence Factors - genetics; Wound healing; Wound infection
• ISSN: 1471-2180; 1471-2180
• DOI: 10.1186/s12866-024-03429-8

Multi-drug resistant Staphylococcus aureus is one of the most common causes of nosocomial and community-acquired infections, with high morbidity and mortality. Treatment of such infections is particularly problematic; hence, it is complicated by antibiotic resistance, and there is currently no reliable vaccine. Furthermore, it is well known that S. aureus produces an exceptionally large number of virulence factors that worsen infection. Consequently, the urgent need for anti-virulent agents that inhibit biofilm formation and virulence factors has gained momentum. Therefore, we focused our attention on an already-approved antibiotic and explored whether changing the dosage would still result in the intended anti-virulence effect. In the present study, we determined the antibiotic resistance patterns and the MICs of oxacillin against 70 MDR S. aureus isolates. We also investigated the effect of sub-MICs of oxacillin (at 1/4 and 1/8 MICs) on biofilm formation using the crystal violet assay, the phenol-sulphuric acid method, and confocal laser scanning microscopy (CLSM). We examined the effect of sub-MICs on virulence factors and bacterial morphology using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and electron microscopy, respectively. Moreover, we studied the effect of sub-MICs of oxacillin (OX) in-vivo using a wound infection model. Oxacillin at 1/2 MIC showed a significant decrease in bacterial viability, while 1/4 and 1/8 MICs had negligible effects on treated bacterial isolates. Treatment of MDR isolates with 1/4 or 1/8 MICs of oxacillin significantly reduced biofilm formation (64% and 40%, respectively). The treated MDR S. aureus with sub-MICs of OX exhibited a dramatic reduction in several virulence factors, including protease, hemolysin, coagulase, and toxic shock syndrome toxin-1 (TSST-1) production. The sub-MICs of OX significantly decreased (P