Elucidation of the genetic mechanisms contributing to moenomycin resistance in actinobacteria

Abstract

Aim. Moenomycins are phosphoglycolipid antibiotics produced almost exclusively by representatives of genus Streptomyces. These antibiotics directly inhibit peptidoglycan glycosyltransferases and are extremely active against cocci. Here we studied how antibiotic-producing actinobacteria protect themselves from toxic action of moenomycins. Methods. Microbiological and molecular genetic approaches were combined to reveal intrinsic levels and distribution of moenomycin resistance across actinobacteria genera, and to pinpoint genes contributing to moenomycin resistance in model strain Streptomyces coelicolor M145. Results. Out of 51 actinobacterial species (90 % of which Streptomyces) being tested, only Streptomyces albus J1074 turned out to be highly susceptible to moenomycin A, although resistant variants can be facilely raised. Several classes of mutations increased level of susceptibility of S. coelicolor to moenomycin, although in no case the latter was equal to what we observed in J1074 strain. Conclusions. Moenomycin resistance is widespread across actinobacteria, and it most likely is caused by a combination factors, such as richly decorated cell wall and organization of divisome apparatus. It is possible that moenomycin resistance mechanisms operating in actinobacteria and pathogenic cocci are different.
 Keywords: moenomycin, antibiotic resistance, peptidoglycan.