Emergence of community-associated methicillin-resistant Staphylococcus aureus ΨUSA300 among Japanese people with HIV, resulted from stepwise mutations in 2010s

Abstract

Although infection with the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 is extremely rare in Japan, the uniquely evolved clone ΨUSA300 has been reported in Japan. An outbreak of a distinct USA300 clone was recently reported in an HIV/AIDS referral hospital in Tokyo. The present study investigated the evolutionary origin and genetic diversity of USA300-related clones causing regional outbreaks among people living with HIV (PLWHIV) in Tokyo. MRSA isolates collected from PLWHIV in an HIV/AIDS referral center in Tokyo were subjected to whole-genome sequencing and their genetic features were compared with those of previously described USA300 MRSA genomes. Of the 28 MRSAs isolated in 2016–2019, 23 (82.1%) were identified as USA300, with 22 (95.6%) of the latter identified as ΨUSA300. Although the genomic structure of ΨUSA300 was identical to the structures of reference USA300 strains, one clade (cluster A) was found to have acquired 29 previously identified lineage-specific mutations in a stepwise manner. The estimated divergence dates of ΨUSA300 and Cluster A were 2009 and 2012, respectively. These findings suggested that the ΨUSA300 clone had spread among PLWHIVs in Tokyo in the early 2010s, with stepwise acquisition of lineage-specific nonsynonymous mutations.

Significant increase in the prevalence of Panton–Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus , particularly the USA300 variant ΨUSA300, in the Japanese community

“…ΨUSA300 was first identified as a USA300 variant that was misclassified as an isolate harboring SCC mec type I by conventional PCR-based SCC mec typing because of deletion in the binding site of a βc primer ( 15 ). The emergence of ΨUSA300 in Japan has been observed in previous studies ( 16 – 18 ). The detection rate of PVL genes among MRSA has increased in community settings in many parts of Japan ( 17 – 20 ).…”

“…2 ). The USA300 and ΨUSA300 strains isolated in this study were expected to show nearly identical profiles for virulence genes for which the detection process was not conducted, including certain of the genes encoding hemolysin, leukotoxin, staphylococcal enterotoxin, and staphylococcal complement inhibitor, considering the results of previous reports ( 16 , 18 ). Meanwhile, The MICs and resistance gene profiles indicated that USA300 and ΨUSA300 tended to harbor different mobile genetic elements ( Table 2 ).…”

“…Notably, the number of ΨUSA300 strains carrying SCC mec type IV with a particular deletion considerably exceeded the number of USA300 strains. Despite few differences between ΨUSA300 and USA300, previous studies have reported that ΨUSA300 strains formed unique clusters through phylogenetic analysis ( 16 , 18 ). Therefore, ΨUSA300 strains isolated in this study were expected to show similar results.…”

“…Although the number of USA300 strains was small, ΨUSA300 was more strongly associated with deep-seated SSTIs than USA300 ( Table 1 ). Several USA300 variants share a common ancestor with USA300 ( 9 , 16 ). ΨUSA300 may have evolved from the same ancestor and subsequently acquired the capability to more frequently cause deep-seated SSTIs than in the USA300.…”