Novel mechanism responsible for high-level macrolide resistance in <em>Moraxella catarrhalis</em>

Abstract

BackgroundHigh-level macrolide-resistant Moraxella catarrhalis strains have been isolated; however, the underlying mechanism has not been well elucidated. We investigated the role of mutations in the 23S rRNA gene and the L4 and L22 ribosomal proteins using spontaneous erythromycin-resistant mutants and transformants.Materials and methodsThe erythromycin-susceptible M. catarrhalis ATCC25238 and clinical isolate Mc19 were used as parental strains. To obtain spontaneous erythromycin-resistant mutants, in vitro stepwise selection was performed using brain–heart infusion agar plates containing various concentrations of erythromycin. The role of the mutations identified in the spontaneous mutants was validated using transformation experiments.ResultsWe obtained two spontaneous mutants with high-level resistance to erythromycin, S25-32-af10 and S19-256-af10, from ATCC25238 and Mc19, respectively. S25-32-af10 exhibited mutations of Q61R in L4 and Insertion98SRADRIS in L22. S19-256-af10 exhibited three C2611T-mutated alleles in the 23S rRNA gene and G65A in L4. Transformants with single mutations identified in S25-32-af10 or S19-256-af10 showed higher erythromycin and azithromycin minimum inhibitory concentrations (MICs) than those of each parental strain. However, transformants with multiple mutations identified in S25-32-af10 or S19-256-af10 showed macrolide MICs similar to those of each parental strain.ConclusionOur results provide the first evidence suggesting that Q61R in L4 and Insertion98SRADRIS in L22 are involved in the synergistic acquisition of high-level resistance to both 14- and 15-member macrolides, and that C2611T in the 23S rRNA gene and G65A in L4 also synergistically contribute toward conferring high-level 14-member macrolide resistance to M. catarrhalis.

An integrated complete-genome sequencing and systems biology approach to predict antimicrobial resistance genes in the virulent bacterial strains of Moraxella catarrhalis

“…Even several studies have found that a mutation in the TonB -dependent receptor expressing gene MCR 0492 may be linked to macrolides susceptibility in M. catarrhalis strains [ 97 ]. Kasai et al [ 98 ] used naturally occurring erythromycin-resistant variants to study the impact of alterations in the 23S rRNA gene and also the L4 and L22 ribosomal subunits. Additionally, the development of rising macrolide-susceptibility M. catarrhalis may be attributed to the A2330T Mutation in the 23S rRNA gene [ 99 ].…”

Mutation of TonB-Dependent Receptor Encoding Gene MCR_0492 Potentially Associates with Macrolides Resistance in Moraxella catarrhalis Isolates

“… 21 Some erythromycin-resistant isolates found mutations in rplD gene and rplV gene encoding ribosomal proteins L4 (V27A/R161C/ Q61R) and L22 (K68T/ Insertion98SRADRIS). 22 , 23 A Chinese study have shown that 23SrRNA gene A2982T, A2796T and A2330T mutations are associated with high resistance to macrolides of Moraxella catarrhalis (MICs:24–256μg/mL), and A2983T mutations are associated with low drug resistance (MICs:0.19–16μg/mL). 14 However, there was no resistance mutation above was observed in two highly resistant isolates of Moraxella catarrhalis in our study.…”

Clarithromycin versus Amoxicillin alone or with Clavulanate in Acute Maxillary Sinusitis: A Meta-analysis of Clinical Trials

“…Shifting patterns of antibiotic resistance are relevant when considering these data. Profiles of resistance will have altered, often substantially, in the intervening years, as evidenced, for example, by the emergence of high-level resistance against macrolides by clinical isolates of Moraxella catarrhalis in Japan [30] and China [31], and by wider shifts in antibiotic resistance around the world [32,33]. Decisions on the use of antibiotics in AMS of presumed bacterial origin should, so far as possible, be guided by the local circumstances of pathogen resistance and by emerging trajectories of resistance development.…”