Mycoplasma bovis isolates from dairy calves in Japan have reduced susceptibility to all approved macrolides, resulting from a point mutation (G748A) combined with multiple species ‐specific nucleotide alterations in 23S rRNA

In this study, 58 M. bovis isolates obtained from Japanese dairy calves all exhibited reduced susceptibility to these macrolides. The widespread reduced susceptibility to the macrolides resulted from a few dominant lineages. All 58 isolates contained the G748A variant in both the rrl3 and rrl4 alleles of 23S rRNA, whereas a reference strain (PG45) did not. G748 localizes in the central loop of domain II (from C744 to A753) of 23S rRNA that participates in binding to mycinose, a sugar residue present in both tylosin and tilmicosin. A number of in vitro selected mutants derived from M. bovis PG45 showed reduced susceptibility to tylosin and tilmicosin, and contained a nucleotide insertion within the central loop of domain II of rrl3 (U747–G748Ins_CU/GU or A743–U744Ins_UA), suggesting that mutations around G748 confer this reduced susceptibility phenotype. However, other Mycoplasma species containing G748A were susceptible to tylosin and tilmicosin. Sequence comparison with Escherichia coli revealed that M. bovis PG45 and isolates harbored five nucleotide alterations (U744C, G745A, U746C, A752C, and A753G) in the central loop of domain II of 23S rRNA, whereas other Mycoplasma species lacked at least two of the five nucleotide alterations. Thus, we concluded that G748 mutation in combination with species‐specific nucleotide alterations in the central loop of domain II of 23S rRNA should be sufficient for reduced susceptibility to tylosin and tilmicosin in M. bovis.
Source: Microbiology and Immunology - Category: Microbiology Authors: Tags: Original Article Source Type: research