Increased Antibiotic Resistance of Methicillin-Resistant USA300 Δ Mutants and a Complementation Study of Δ Mutants Using Synthetic Phenol-Soluble Modulins.

Phenol-soluble modulins (PSMs) are responsible for regulating biofilm formation, persister cell formation, expression, host cell lysis, and anti-bacterial effects. To determine the effect of deletion on methicillin-resistant , we investigated deletion mutants including Δ, Δ, and Δ;. These mutants exhibited increased β-lactam antibiotic resistance to ampicillin and oxacillin that was shown to be caused by increased Nacetylmannosamine kinase () mRNA expression, which regulates persister cell formation, leading to changes in the pattern of phospholipid fatty acids resulting in increased anteiso-C, and increased membrane hydrophobicity with the deletion of PSMs. When synthetic PSMs were applied to Δ and Δ mutants, treatment of Δ with PSMα1-4 and Δ with PSMβ1-2 restored the sensitivity to oxacillin and slightly reduced the biofilm formation. Addition of a single fragment showed that α1, α2, α3, and β2 had an inhibiting effect on biofilms in Δ; however, β1 showed an enhancing effect on biofilms in Δ. This study demonstrates a possible reason for the increased antibiotic resistance in mutants and the effect of PSMs on biofilm formation.