Genomic Surveillance and Phenotypic investigation of Methicillin-Resistant Staphylococcus Aureus (MRSA) in Hospital Canselor Tuanku Muhriz (HCTM)

Abstract

Pathogen surveillance is key to staying ahead of the growing threat of antimicrobial resistance (AMR). Molecular surveillance of methicillin-resistant Staphylococcus aureus (MRSA) isolated from Hospital Canselor Tuanku Muhriz (HCTM) revealed clonal replacement of SCCmec type III-SCCmercury to SCCmec type IV strains; however, the reasons behind this phenomenon are still unknown. This study aimed to identify factors associated with the clonal replacement via whole-genome sequencing (WGS) and phenotypic comparisons (growth rate, resistance to desiccation, survival in vancomycin sub-minimum inhibitory concentration (MIC), competitive fitness) of tested strains and review of HCTM antimicrobial stewardship (AMS) and infection prevention control (IPC) policies. Sixteen representative HCTM MRSA strains isolated in four-year intervals from 2005-2017 were subjected to WGS and phenotypic investigations. While MRSAs with the same STs shared similar core and accessory genomes, majority of the strains isolated in earlier years of the surveillance (2005, 2009 and 2013; n = 4, 4 and 3 respectively) were resistant to many antibiotics, from the ST239-III lineage, harboured multiple AMR and virulence genes compared to the ST22-IV (isolated in 2013 and 2017, n = 1 and 3 respectively) and ST6-IV strains (isolated in 2017, n = 1). Phenotype investigations involving more MRSA strains revealed that both ST22-IV and ST6-IV grew significantly faster and were more resistant to desiccation than ST239-III (p < 0.05), even though the later clone survive better post-vancomycin exposure. Intriguingly, ST22-IV was outcompeted by ST239- III in broth co-cultures; though it survived better when desiccated together with ST239- III. Higher desiccation tolerance of ST22-IV, together with reduction of antibiotic selection pressure in HCTM (due to AMS and IPC policies) during 2005 – 2017 may have provided it a competitive edge in replacing the previously dominant ST239-III. Strengthening the HCTM MRSA surveillance via genomics and phenotypic investigations can provide better insights into the pathogen’s evolution and clonal changes, allowing public health authorities to stay alert and take appropriate countermeasures.