title: Induction of MRSA Biofilm by Low-Dose β-Lactam Antibiotics: Specificity, Prevalence and Dose-Response Effects.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital- and community-associated infections. The formation of adherent clusters of cells known as biofilms is an important virulence factor in MRSA pathogenesis. Previous studies showed that subminimal inhibitory (sub-MIC) concentrations of methicillin induce biofilm formation in the community-associated MRSA strain LAC. In this study we measured the ability sub-MIC concentrations of eight other β-lactam antibiotics and six non-β-lactam antibiotics to induce LAC biofilm. All eight β-lactam antibiotics, but none of the non-β-lactam antibiotics, induced LAC biofilm. The dose-response effects of the eight β-lactam antibiotics on LAC biofilm varied from biphasic and bimodal to near-linear. We also found that sub-MIC methicillin induced biofilm in 33 out of 39 additional MRSA clinical isolates, which also exhibited biphasic, bimodal and linear dose-response curves. The amount of biofilm formation induced by sub-MIC methicillin was inversely proportional to the susceptibility of each strain to methicillin. Our results demonstrate that induction of biofilm by sub-MIC antibiotics is a common phenotype among MRSA clinical strains and is specific for β-lactam antibiotics. These findings may have relevance to the use of β-lactam antibiotics in clinical and agricultural settings.
authors.affiliation: Department of Biology, American University, Washington DC, USA.
authors.forename: Mandy
authors.initials: M
authors.lastname: Ng
authors.affiliation: Department of Biology, American University, Washington DC, USA.
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Epstein
authors.affiliation: Department of Biology, American University, Washington DC, USA.
authors.forename: Mary T
authors.initials: MT
authors.lastname: Callahan
authors.affiliation: Department of Biology, American University, Washington DC, USA.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Piotrowski
authors.affiliation: Division of Infectious Diseases, Department of Medicine, The George Washington University, Washington DC, USA.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Simon
authors.affiliation: Division of Infectious Diseases, Department of Medicine, The George Washington University, Washington DC, USA.
authors.forename: Afsoon D
authors.initials: AD
authors.lastname: Roberts
authors.affiliation: Department of Pathology, The George Washington University, Washington DC, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Keiser
authors.affiliation: Department of Biology, American University, Washington DC, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kaplan
keywords: MRSA; Staphylococcus aureus; antibiotic; bimodal; biofilm; biphasic; subminimal inhibitory