Jakub Lenart
Charles University in Prague, Czech Republic
Title: The role of the ABC-F proteins, Vga(A) and Msr(A), in antibiotics resistance in staphylococci
Biography
Biography: Jakub Lenart
Abstract
Staphylococcal ABC-F proteins Vga(A)LC and Msr(A) confer resistance either to lincosamides (L), streptogramins A (SgA) and pleuromutilines or to 14- and 15-membered macrolides and streptogramines B, respectively. All these antibiotics bind near peptidyl transferase centre in 50S ribosomal subunit and inhibit translation. Previous experiment has shown that 15 amino acid stretch of the Vga(A) interdomain linker is important for the antibiotic specificity of Vga(A) proteins. Substitutions L212S, G219V, A220T and G226S, clustered in the stretch, were responsible for the changes in resistance to SgA and L. It has been demonstrated in vitro, that ABC-F proteins mediate antibiotic resistance through interaction with ribosomes (Sharkey,2016). However, in our in vitro experiments, we confirmed that both proteins – Vga(A)LC , Msr(A) co-localize with membrane fractions of the cells. Therefore, it may be assumed that the proteins cooperate specifically with the ribosomes on the membrane, or, alternatively, the resistance mechanism is more complex, including also a cooperation of ABC-F proteins with a transmembrane partner. Vga(A)LC and Msr(A) might influence binding of lincomycin and erythromycin to the ribosomes in a similar way. Therefore, the functional interference of these two proteins is expected. To test this hypothesis we determined the resistance to lincomycin and erythromycin in the strain expressing both proteins. We found that activity of Msr(A) was not inhibited by Vga(A)LC as we expected but by the presence of subinhibitory concentration of lincomycin. Thus, usage of lincomycin may help in suppression of erythromycin resistance, conferred by Msr(A).