Modulation of azithromycin activity against monospecies and binary biofilms <I>Staphylococcus aureus</I> and <I>Kytococcus schroeteri</I> by norepinephrine

The effect of norepinephrine as a substance modulator of the activity of the antibiotic azithromycin in relation to monospecies and binary biofilms of representatives of the human microbiota Staphylococcus aureus and Kytococcus schroeteri was studied in various model systems. It has been shown that the hormone at a concentration of 3.55 µM, depending on the cultivation system and incubation time, is capable of both enhancing and weakening the effects of azithromycin at subinhibitory concentrations (0.001 and 4 µg/ml). In the case of rapidly formed biofilms, norepinephrine weakens the inhibitory effect of the antibiotic, while in the presence of the full stage of adhesion, on the contrary, the hormone enhances the inhibitory effect of the antibiotic. No less important is the factor of interaction between two microorganisms in the community, since the presence of K. schroeteri in the community changes the effect of 4 μg/ml azithromycin in combination with norepinephrine on S. aureus . It has been shown that azithromycin and norepinephrine, as well as their combinations, are able to change the expression of resistance genes not only to macrolides (increased expression of the mrx gene by a combination of 4 μg/ml azithromycin and 3.55 μM norepinephrine), but also to fluoroquinolones (decreased expression of the arlR gene and increased mdtK).