Whole Genome Sequenced-based Characterization and Determination of quinolone Resistance Among Methicillin-resistant and Methicillin-susceptible S. aureus isolates from Patients Attended Regional Referral Hospitals in Tanzania

Abstract

Abstract Background The emergency of multidrug-resistant S. aureus (MRSA) strains, driven by acquisition of resistance gene in mecA imposes a substantial challenge in the treatment and control of their related infections. Despite the fact that Quinolones have historically been effective against both MRSA and methicillin-susceptible S. aureus (MSSA) strains, the escalating rising of quinolones resistance among S. aureus isolates particularly in MRSA, has severely curtailed their potency and further narrow down the therapeutic options. This study aimed at determining the burden of MRSA among isolates, their resistance profile, genotypic characterization and determining the molecular relatedness through construction of phylogenetic tree. Material and Methods Archieved clinical S. aureus isolates from a descriptive cross-sectional study involving six regional referral hospitals in Dodoma, Songea, Kigoma, Kitete, and Morogoro in mainland and Mnazi Mmoja in Zanzibar were analyzed. Bacterial identification was performed using both classical microbiology and whole genome sequencing on Illumina Nextseq 550 Sequencer. Species identification was done using KmerFinder 3.2, Multilocus Sequence Types using MLST 2.0, SCCmec type using SCCmecFinder 1.2, resistance genes using ResFinder 4.1, and phylogenetic relatedness using CSI Phylogeny 1.4. Results Out of the 140 isolates analyzed, 69 (49.3%) were identified as MRSA, with 57 (82.6%) exhibiting quinolone resistance. Conversely, 71 isolates were identified as MSSA, and none of them exhibited resistance to quinolone. Spa-typing revealed 6 spa types, with t355, t1476, and t498 being most common. Moreover, all (69) MRSA were found to carry SCCmec type IV. The isolates exhibited 14 different sequence types (ST). Notably, ST152 was prevalent 50(70%) among MSSA while ST8 was the predominant 58(84%) sequence type among MRSA. The antimicrobial resistance profile revealed at least three horizontally acquired resistance genes, with blaZ, dfrG, tet(K), and aac (6’)-aph (2’’) genes being highly prevalent. Conclusion There is a high genetic diversity among the S. aureus isolates existing in Tanzania regional hospitals, with a concerning burden of quinolone resistance in MRSA isolates. The diversity in resistance genes among MRSA lineages emphasizes the necessity for development of sustainable antimicrobial stewardship and surveillance to support evidence-based guidelines for the management and control of MRSA infections in both community and hospital settings.