Gentamicin-resistance determinants confer background-dependent hygromycin B resistance

Micromonospora strains that produce aminoglycoside antibiotics have a high level of resistance to their own products and to structurally similar antib iotics with a 4,6-disubstituted deoxystreptamine aminocyclitol component su ch as neomycin, kanamycin, or gentamicin, but these strains remain suscepti ble to other aminoglycosides such as neomycin and apramycin, in which the a minocyclitol component has different types of substitutions. Therefore, it was surprising that the aminoglycoside-producing Micromonospora strains exa mined here also showed high-level resistance to hygromycin B, in spite of t he fact that this compound has a structurally different aminocyclitol compo nent and a mode of antibacterial action that was also shown to differ somew hat from the mode of action of gentamicin-type antibiotics. When the resist ance genes sgm and grm were cloned in Streptomyces lividans and E. coli, th ey 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 ob served with other genes from related genera that are also responsible for a minoglycoside resistance due to methylation of 16S rRNA: of these genes, on ly kgm assisted expression of hygromycin B resistance and only in the backg round of M. melanosporea. A possible mechanism for the background dependent of hygromycin B resistance is discussed.