Induction of macrolide resistance inMycoplasma gallisepticumin vitro and its resistance-related mutations within domain V of 23S rRNA

Abstract

Antibiotic-resistant mutants of Mycoplasma gallisepticum were selected in vitro from the susceptible strains S6 and BG44T by serial passages in stepwise concentrations of erythromycin, tylosin, or tilmicosin. High resistance to erythromycin or tilmicosin developed readily, whereas resistance to tylosin developed only after greater numbers of passages. Three mutants selected by each selector antibiotic were cloned and detected, and all cloned mutants exhibited cross-resistance to the three selector antibiotics as well as to lincomycin. Portions of the genes encoding domain V of 23S rRNA of the cloned mutants were amplified by PCR, and their nucleotide sequences were compared to those of the susceptible parent strains. Five of the six mutants selected by erythromycin harbored an A2058G (Escherichia coli numbering) mutation in one of the two 23S rRNA. One of the six mutants selected by erythromycin harbored a G2057A mutation and an A2059G mutation in the other 23S rRNA. In tilmicosin-selected mutants, two mutations, A2058G and A2503U, occurred in one of the two 23S rRNA. No mutation was detected in the two 23S rRNA of tylosin-selected mutants with low-level resistance. Mutations at homologous locations in the 23S rRNA of other macrolide-resistant bacteria indicate that the phenotype of macrolide resistance occurring in M. gallisepticum is strongly associated with point mutations in domain V of 23S rRNA.

Antibiotic susceptibility profiles of Mycoplasma sp. 1220 strains isolated from geese in Hungary

“…with one or two mutations) than to other macrolides. The same phenomenon was described in other Mycoplasma species as well [24]. Out of the three macrolides examined in the study, tylvalosin proved to be the most effective agent against M .…”

“…However, M. gallisepticum could develop resistance rapidly to these compounds, especially to tilmicosin [24]. Earlier, the MIC 50 values in M. sp.…”

Mutations of domain V in 23S ribosomal RNA of macrolide-resistant Mycoplasma gallisepticum isolates in Egypt

“…In nucleotide position 2057, a guanine to adenine transition was reported in three erythromycinresistant M. gallisepticum isolates. Actually, those mutations were the most frequently reported in the erythromycin-resistant isolates of M. gallisepticum genetically characterized [17,31] and have been previously reported as hot spots for macrolide resistance in other mycoplasmas [32,33]. Based on our results, transition can be considered the predominant type of mutation in M. gallisepticum.…”

Determination of the Mutant Selection Window and Evaluation of the Killing of Mycoplasma gallisepticum by Danofloxacin, Doxycycline, Tilmicosin, Tylvalosin and Valnemulin

“…M . gallisepticum could acquire resistance to tilmicosin and valnemulin through 23S rDNA point mutations[30, 31]. Despite the mechanism of reduced susceptibility and antimicrobial drug class, MPC defines antimicrobial drug concentrations that block the growth of resistant sub-populations from high density bacterial populations.…”