Differences in 23S ribosomal RNA mutations between wild-type and mutant macrolide-resistant Chlamydia trachomatis isolates

Abstract

Abstract. The aim of the present study was to determine the in vitro susceptibility of wild-type and mutant clinical isolates of Chlamydia (C.) trachomatis strains to erythromycin, azithromycin and josamycin, and to identify the resistance-conferring 23S ribosomal (r)RNA mutations in the isolates. The wild-type resistant isolates were defined as those with minimum inhibitory concentration values above the tissue concentration of the antibiotic in the urogenital system. Furthermore, all resistant C. trachomatis isolates were exposed to sub-inhibitory concentrations of macrolides, and 13 resistant mutants were selected following serial passages. Among the 8 wild-type isolates that were resistant to erythromycin, 3 isolates had a mutation at T2611C in the 23S rRNA gene while the others did not show any 23S rRNA mutations. The selected mutant isolates showed a 4-to 16-fold reduction in in vitro sensitivities. With regard to the mutant strains, the T2611C mutation was found in 10 isolates, A2057G mutation in 6 isolates, and A2059G mutation in 1 isolate. Thus, the macrolide-resistant isolates of the wild-type strain had different mutations from those selected by exposure to sub-inhibitory concentrations of macrolides. Also, since 23S rRNA mutations were not identified in certain isolates, it was considered that other molecular mechanisms may also be responsible for the macrolide resistance of C. trachomatis.

Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion

“…Many bacterial species are becoming fully resistant to all frontline drugs, including sexually transmitted bacteria such as Neisseria gonorrhoeae and Mycoplasma genitalium, which commonly coinfect with C. trachomatis (Unemo and Shafer 2011). Despite treatment failures of C. trachomatis infections with recommended therapeutic antimicrobials being reported (Hogan et al 2004), isolated reports of genomically conferred resistance (Misyurina et al 2004;Jiang et al 2015), and the ease with which resistance can be selected for in vitro by exposure to subinhibitory antimicrobial concentrations (Sandoz and Rockey 2010), little is known about the prevalence, if any, of circulating resistance traits.…”

Determining the Antibiotic Resistance of Bacterial Pathogens in Sexually Transmitted Diseases

“…Possible mechanisms underlying drug resistance should be investigated in the future in order to understand the resistance of isolates exhibiting no mutation in the peptidyl transferase region of the 23S rRNA gene. The merits of the Chinese study are that, for the first time, wild-type macrolide-resistant C. trachomatis strains have been observed in vitro, and for the first time, A2057G and A2059G mutations in the peptidyl transferase region of the 23S rRNA gene have been found in C. trachomatis with selective macrolide resistance [13].…”

“…Genotypes were determined by comparison of resulting sequences with reference C. trachomatis omp1 sequences in the GenBank database. Conclusions were that the mechanism responsible for heterotypic resistance in C. trachomatis remains unknown, being possible that the observed multidrug resistance to be phenotypic rather than genotypic in nature since the molecular targets of azithromycin, doxycycline and ofloxacin are quite different, and it is highly unlikely that a single or a limited number of gene mutation(s) could be responsible for simultaneous resistance to these diverse agents [13,48].…”

“…Investigating mutations in the 23S rRNA gene of macrolide-resistant isolates of wild-type C. trachomatis obtained from clinical samples and mutant strains selected using subinhibitory concentrations of the macrolides were the objective of another recent study [13] in which a set of resistant clinical isolates of C. trachomatis obtained from patients attending the Tianjin Institute of Venerology (Tianjin, China) during 2005 2008 was differentiated into wild-type and mutant strains, the 23S rRNA mutations in the isolates then being identified. Each patient was sampled for only one isolate, the antimicrobial agents examined being erythromycin, azithromycin and josamycin.…”

“…It is assumed that mutations in a specific region of the 23S rRNA play a major role in inducing resistance to macrolides as a result of their interaction with the ribosomes [12,13].…”