Effect of adamantane derivative on expression of biofilm-associated genes in methicillin-resistant Staphylococcus aureus

Abstract

In the etiology of nosocomial infections, the leading role belongs to such microorganisms as Staphylococcus aureus. Insufficient effectiveness of antimicrobial chemotherapy and practical absence of drugs with an antibiofilm activity encourage the development of new remedies. The study presents results on antibiofilm activity of the adamantane derivative 1-[4-(1-adamantyl)phenoxy]-3-(N-benzyl,N-dimethylamino)-2-propanol chloride (KVM-97) against methicillin-resistant S. aureus (MRSA) and the effect of this agent on the expression genes that provide regulatory and biosynthetic functions of biofilms. The ability of adamantane derivative to affect S. aureus biofilms was tested by microtiter dish biofilm formation assay. The effect of KVM-97 on expression level of genes icaA, icaD, icaR, agrA, sarA, clfB, fib, fnbB, ebpS, and eno was detected by the real-time PCR. The KVM-97 inhibits the formation of S. aureus biofilms at 5.0 MIC by 95.1 % and at 0.5 MIC – by 22.4 %. Under the action of KVM-97, destruction of the mature biofilms was not detected. It inhibits expression of the icaADBC operon and agrA gene, as well as stimulates a transcriptional activity of the icaR regulator. Subinhibitory concentrations of the KVM-97 significantly inhibit the expression of clfB, fib, fnbB, ebpS, and eno, but does not change the sarA gene expression. Thus, 1-[4-(1-adamantyl)phenoxy]-3-(N-benzyl,N-dimethylamino)-2-propanol chloride shows pronounced antibiofilm activity against MRSA at the early stages of the biofilm forming. This effect may be relating to influence on the expression of genes that regulate adhesion to the substrate and formation of S. aureus biofilms.