Association of Tandem Repeat Number Variabilities in Subunit S of the Type I Restriction-Modification System with Macrolide Resistance in Mycoplasma pneumoniae

Mycoplasma pneumoniae is one of the major pathogens responsible for pneumonia in children. Modern molecular genetics has advanced both the management and the epidemiologic study of this disease. Despite these advancements, macrolide resistance remains a global threat in the management of M. pneumoniae infection, for which the genetic background remains unrevealed. In this study, the result of whole genome analysis of 20 sequence type 3 (ST3) M. pneumoniae strains were examined to investigate the gene(s) associated with macrolide resistance. Overall, genetic similarities within M. pneumoniae, and especially ST3, were very high (over 99.99 %). Macrolide resistant ST3 strains shared 20 single nucleotide polymorphisms, of which one gene (mpn085) was found to be associated with resistance. BLAST comparison of M. pneumoniae revealed regular tandem repeat number variabilities between macrolide-susceptible and resistant strains for genes coding the Type I restriction-modification (R-M) system of subunit S (HsdS). Of the ten known HsdS genes, macrolide resistance was determined by the unique tandem repeat of mpn085 and mpn285. In conclusion, the use of whole genome sequencing (WGS) to target macrolide resistance in M. pneumoniae indicates that the determinant of macrolide resistance is variabilities in the tandem repeat numbers of the type I R-M system in subunit S.