Unveiling the molecular basis of antimicrobial resistance in Staphylococcus aureus from the Democratic Republic of the Congo using whole genome sequencing.

Staphylococcus aureus from sub-Saharan Africa is frequently resistant to antimicrobial agents that are commonly used to treat invasive infections in resource-limited settings. The underlying mechanisms of resistance are largely unknown. We therefore performed whole genome sequencing (WGS) on S. aureus from the Democratic Republic of the Congo (DRC) to analyse the genetic determinants of antimicrobial resistance. One hundred S. aureus samples were collected from community-associated asymptomatic nasal carriers in the metropolitan area of Kinshasa, DRC, between 2013 and 2014. Phenotypic resistance against 15 antimicrobial agents was compared to the genotypic results that were extracted from WGS data using Mykrobe predictor and the SeqSphere(+) software that screened for 106 target genes associated with resistance. Isolates were phenotypically resistant against penicillin (97%, n=97), trimethoprim (72%, n=72) and tetracycline (54%, n=45). Thirty-three isolates (33%) were methicillin-resistant S. aureus (MRSA). Of these, nine isolates (27.3%) were oxacillin-susceptible MRSA (OS-MRSA) and belonged to ST8 (t1476). The Y195F mutation of FemA was associated with OS-MRSA (p 0.015). The majority of trimethoprim resistant isolates carried dfrG. Tetracycline resistance was associated with tet(K). The concordance between phenotypic susceptibility testing and both WGS analysis tools was similar and ranged between 96% and 100%. In conclusion, a high proportion of OS-MRSA in the DRC was linked to mutations of FemA. Genotypic and phenotypical antimicrobial susceptibility testing showed high concordance. This encourages the future use of WGS in routine antimicrobial susceptibility testing.