Profile and evolution of antimicrobial resistance genes in Staphylococcus aureus whole genomes in Africa revealed by phylogeography and bioinformatics
摘要
The elaboration of antimicrobial resistance genes (ARGs) in Staphylococcus aureus is a significant public health concern. Despite this concern, the spread and diversity of the ARGs in S. aureus are not fully understood. This study is the first report of the diversity and evolution of ARGs in whole genomes of S. aureus in Africa using a combination of phylogeography and bioinformatics. Whole genomes of S. aureus isolates from Africa were retrieved from the National Centre for Biotechnology Information (NCBI) and were used to infer ARGs diversity and evolution across Africa using the CARD (Comprehensive Antibiotic Resistance Database) and BEAST (Bayesian Evolutionary Analysis Sampling Trees) tools, respectively. The metadata revealed diverse sources from which S. aureus was isolated. Out of the 95 whole genomes retrieved, 75 (79%) came from human (blood, pus, urine, wounds, among others) samples. The top ten (10) most abundant AROs out of thirty-three (33) annotated were norC (n = 150), arlR (n = 91), mrrA (n = 90), sepA (n = 88), mepR (n = 85), S. aureus LmrS (n = 83), kdpD (n = 77), vanT gene in vanG cluster (74), S. aureus norA (n = 69), and S. aureus FosB (n = 47). The top 10 gene families out of 22 annotated were the major facilitator superfamily (MFS) antibiotic efflux pump (n = 524), MATE transporter (n = 102), SMR antibiotic efflux pump (n = 92), ABC-MFS (n = 91), glycopeptide resistance gene cluster; vanT (n = 74), kdpDE (n = 70), fosfomycin thiol transferase (n = 47), antibiotic-resistant murA transferase (n = 36), trimethoprim-resistant dihydrofolate reductase dfr (n = 27), and antibiotic-resistant GlpT & fluoroquinolone-resistant gyrA (n = 25 each). The mechanisms of action of the AROs were antibiotic efflux (AE), antibiotic inactivation (AI), antibiotic target alteration (ATA), antibiotic target protection (ATP), antibiotic target replacement (ATR), and antibiotic target alteration/target replacement (A-A) with pooled frequencies of 887, 82, 191, 17, 39, and 4, respectively. Phylogeography analysis showed the spread of S. aureus harbouring ARGs across Africa, but only for countries (n = 11) for which full S. aureus genomes were available and retrieved. Furthermore, the West and East Africa regions were found to have been hubs for the spread of the ARGs. Given that all the genomes possessed ARGs, our findings further buttress the role of the other animals and the environment in their spread. In addition, the findings in this study can further inform the best choice of antibiotics to be used in the treatment of S. aureus infections and future surveillance studies.