Genomic-transcriptomic analysis of Staphylococcus aureus biofilm formation under sub-MIC antibiotic exposure

Antibiotics are widely used in animal husbandry to ensure the health of livestock, leading to the exposure of microorganisms to accumulated sub-lethal concentrations (sub-MICs) of antibiotics in meats. This study aimed to investigate the effects and mechanisms of sub-MICs of commonly used antibiotics on the biofilm formation of a S. aureus strain Guangzhou-SAU071 which displays weak biofilm formation despite harboring biofilm-associated genes. CV and MTS assays were used to determine biofilm biomass and cell viability, respectively. Dual-omics sequencing combining genomics and transcriptomics was used to study the global expression changes. Expression of biofilm and two-component system associated genes was further verified by RT-qPCR. Biofilm formation of Guangzhou-SAU071 was enhanced under sub-MIC of ciprofloxacin (2 μg/mL) and streptomycin (128 μg/mL). Nearly half of the genes associated with biofilm formation, cell wall anchoring, and two-component systems exhibited significant differential expression under sub-MIC of ciprofloxacin and streptomycin. As concluded, sub-MIC of ciprofloxacin and streptomycin enhanced biofilm formation of S. aureus, possibly due to its regulation on biofilm and two-component system associated genes.