Gentamicin-Resistance Determinants Confer Background-Dependent Hygromycin B Resistance

ABSTRACT Micromonospora strains that produce aminoglycoside antibiotics have a high level of resistance to their own products and to structurally similar antibiotics with a 4,6-disubstituted deoxystreptamine aminocyclitol component such as neomycin, kanamycin, or gentamicin, but these strains remain susceptible to other aminoglycosides such as neomycin and apramycin, in which the aminocyclitol component has different types of substitutions. Therefore, it was surprising that the aminoglycoside-producing Micromonospora strains examined here also showed high-level resistance to hygromycin B, in spite of the fact that this compound has a structurally different aminocyclitol component and a mode of antibacterial action that was also shown to differ somewhat from the mode of action of gentamicin-type antibiotics. When the resistance genes sgm and grm were cloned in Streptomyces lividans and E. coli , they conferred resistance to the expected aminoglycoside compounds but not to hygromycin B. In contrast, introduction of the same resistance genes to M. melanosporea produced resistance to hygromycin B as well. Such an apparent strain dependence in the expression of hygromycin B resistance was also observed with other genes from related genera that are also responsible for aminoglycoside resistance due to methylation of 16S rRNA: of these genes, only kgm assisted expression of hygromycin B resistance and only in the background of M. melanosporea . A possible mechanism for the background dependent of hygromycin B resistance is discussed.