Drivers of methicillin-resistant Staphylococcus aureus (MRSA) lineage replacement in China

Abstract

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear. Methods Here, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes. Results ST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role of chp in increasing the virulence potential of ST59 by creating Δchp knockout mutants, confirming that ST59 can carry chp without a measurable impact on fitness. Conclusions Our results suggest that the ongoing replacement of ST239 by ST59 in China is not associated to higher AMR carriage or biofilm production. However, the increase in ST59 prevalence is concerning since it is linked to a higher potential for virulence, aided by the carriage of the chp gene.

Genome Evolution of Invasive Methicillin-Resistant Staphylococcus aureus in the Americas

“…It is also possible that other low-frequency clones have started to increase in frequency during this time, competing with the dominant lineages albeit still undetected. Local clonal expansion followed by replacement of contemporary lineages was previously reported in S. aureus ST239 by STs 5 and 228 in Hungary ( 38 ) and by ST59 in China ( 39 ). We did not find evidence of replacement by rare genotypes from our data set; however, this may be due to the sampling strategies used in our data set that that could have introduced biases in characterization of common and rare lineages.…”

Comparison of Molecular Characteristics Between Methicillin-Resistant and -Susceptible Staphylococcus aureus Clinical Isolates by Whole-Genome Sequencing

“…A recent study indicated that the ongoing replacement of ST239 by ST59 in China, is probably due to the carriage of the chp gene that enhances ST59 virulence activity. 25 Up now, the transmission success of ST59 clones in hospital settings remains unclear. Jin et al suggested that clonal transmission was putatively associated with the intrinsic physiological properties of ST59, rather than with its resistance to antibiotics.…”

Multiple hypervirulent methicillin-sensitiveStaphylococcus aureuslineages contribute towards poor patient outcomes in orthopedic device-related infections

“…Since the emergence and epidemic spread of USA300 (CC8) clone in the early 2000s (30, 71, 72), CA-lineages have dominated infection surveillance studies (19, 71, 72). CA-lineages are typically thought to carry larger -more cumbersome, and less resistant -SCC mec types I, II and III, and often carry toxin genes such as the PVL genes.…”

“…Hypervirulent pandemic clonal lineages have helped spread S. aureus around the world and the geographic distribution of many lineages is dynamic, with different lineages dominating infections in specific global regions (18, 19). Waves of MRSA lineages have risen and been replaced since the emergence of MRSA in the 1940s (18, 20).…”