Abstract
Although previous studies have confirmed that 23S rRNA gene mutation could be responsible for most of macrolide resistance in M. catarrhalis, a recent study suggested otherwise. Next generation sequence based comparative genomics has revolutionized the mining of potential novel drug resistant mechanisms. In this study, two pairs of resistant and susceptible M. catarrhalis isolates with different multilocus sequence types, were investigated for potential differential genes or informative single nucleotide polymorphisms (SNPs). The identified genes and SNPs were evaluated in 188 clinical isolates. From initially 12 selected differential genes and 12 informative SNPs, 10 differential genes (mboIA, mcbC, mcbI, mboIB, MCR_1794, MCR_1795, lgt2B/C, dpnI, mcbB, and mcbA) and 6 SNPs (C619T of rumA, T140C of rplF, G643A of MCR_0020, T270G of MCR_1465, C1348A of copB, and G238A of rrmA) were identified as possibly linked to macrolide resistance in M. catarrhalis. Most of the identified differential genes and SNPs are related to methylation of ribosomal RNA (rRNA) or DNA, especially MCR_0020 and rrmA. Further studies are needed to determine the function and/or evolution process, of the identified genes or SNPs, to establish whether some novel or combined mechanisms are truly involved in M. catarrhalis macrolide resistance mechanism.
Highlights
NR_103214.1) mutation was related to high-level macrolide-resistance[10]
In order to investigate potential novel mechanisms involved in macrolide resistance by M. catarrhalis, with special emphasis on new relevant genes or informative single nucleotide polymorphisms (SNPs), we studied in detail 2 macrolide resistant and 2 susceptible M. catarrhalis isolates using genomic sequencing
multilocus sequence typing (MLST) analyses of the 2 pairs of susceptible and resistant M. catarrhalis isolates studied in detail, showed that each of the four genomes represented a different sequence type (ST), including NP-ST-4 (NP-ST: Denotes sequence types not present in the MLST database at the time of analysis), NP-ST-5 (NP-ST: Denotes sequence types not present in the MLST database at the time of analysis), ST312, and ST327
Summary
The details of the two susceptible isolates are as follows:. (1) Strain 13R13726 was M. catarrhalis isolated in 2013 from a purulent sputum of a 33 year old outpatient woman with lower respiratory tract infection. (2) Strain 11XR1696 was an M. catarrhalis isolate with erythromycin and azithromycin MICs of 0.125 g/L each, and was isolated in 2011 from a 40-year-old woman admitted in hospital with lower respiratory tract infection. (1) Strain 13R13685 was M. catarrhalis with erythromycin and azithromycin MICs of >2 56 g/L each This organism was isolated in 2013 from the purulent sputum of a 61-year-old outpatient man with chronic obstructive pulmonary disease. (2) Isolate 11XR4410 was M. catarrhalis with erythromycin and azithromycin MICs of >256 g/L each, and was isolated from the purulent sputum of a 62-year-old inpatient with lower respiratory tract infection
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