title: Characterization of in vivo-acquired resistance to macrolides of Mycoplasma gallisepticum strains isolated from poultry.
abstract: The macrolide class of antibiotics, including tylosin and tilmicosin, is widely used in the veterinary field for prophylaxis and treatment of mycoplasmosis. In vitro susceptibility testing of 50 strains of M. gallisepticum isolated in Israel during the period 1997-2010 revealed that acquired resistance to tylosin as well as to tilmicosin was present in 50% of them. Moreover, 72% (13/18) of the strains isolated from clinical samples since 2006 showed acquired resistance to enrofloxacin, tylosin and tilmicosin. Molecular typing of the field isolates, performed by gene-target sequencing (GTS), detected 13 molecular types (I-XIII). Type II was the predominant type prior to 2006 whereas type X, first detected in 2008, is currently prevalent. All ten type X strains were resistant to both fluoroquinolones and macrolides, suggesting selective pressure leading to clonal dissemination of resistance. However, this was not a unique event since resistant strains with other GTS molecular types were also found. Concurrently, the molecular basis for macrolide resistance in M. gallisepticum was identified. Our results revealed a clear-cut correlation between single point mutations A2058G or A2059G in domain V of the gene encoding 23S rRNA (rrnA, MGA_01) and acquired macrolide resistance in M. gallisepticum. Indeed, all isolates with MIC ≥ 0.63 μg/mL to tylosin and with MIC ≥ 1.25 μg/mL to tilmicosin possess one of these mutations, suggesting an essential role in decreased susceptibility of M. gallisepticum to 16-membered macrolides.
authors.affiliation: Mycoplasma Unit, Division of Avian and Fish Diseases, Kimron Veterinary Institute, Bet Dagan, 50250, Israel. innal@moag.gov.il.
authors.forename: Irena
authors.initials: I
authors.lastname: Gerchman
authors.forename: Sharon
authors.initials: S
authors.lastname: Levisohn
authors.forename: Inna
authors.initials: I
authors.lastname: Mikula
authors.forename: Lucía
authors.initials: L
authors.lastname: Manso-Silván
authors.forename: Inna
authors.initials: I
authors.lastname: Lysnyansky
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000494:pharmacology*; D018390:Gene Targeting / Q000662:veterinary; D005798:Genes, Bacterial; D007557:Israel / Q000453:epidemiology; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D008969:Molecular Sequence Data; D058889:Molecular Typing / Q000662:veterinary; D009175:Mycoplasma Infections / Q000453:epidemiology / Q000382:microbiology / Q000662:veterinary*; D045686:Mycoplasma gallisepticum / Q000187:drug effects* / Q000235:genetics; D010802:Phylogeny; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011201:Poultry Diseases / Q000453:epidemiology* / Q000382:microbiology; D012338:RNA, Ribosomal, 23S / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012621:Seasons; D015645:Tylosin / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D012338:RNA, Ribosomal, 23S; D012269:Ribosomal Proteins; D000077422:Enrofloxacin; C052319:tilmicosin; D015645:Tylosin