Whole genome sequencing revealed high proportions of ST152 MRSA among clinical Staphylococcus aureus isolates from ten hospitals in Ghana

Abstract

Previous studies in Ghana indicated low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and predominance of ST152 methicillin-susceptible S. aureus (MSSA) among clinical isolates. ST152 MRSA clones are associated with severe infections and epidemics. Using whole genome sequencing (WGS), 159 S. aureus isolated from clinical sources (wound, blood, urine, ear, abscess, umbilical cord, eye, vaginal samples, and others) from 10 hospitals across Ghana were investigated. mecA (gene for methicillin resistance) was detected in 38% of the isolates. Panton-Valentine leucocidin toxin (PVL) gene occurred in 65% isolates, with 84% of the MRSA's harboring the PVL gene. ST152 was the major clone, with 74% harboring the mecA gene. Other MRSA clones detected were ST5, ST5204, ST852, and ST1. MSSA clones included ST3249, ST152, ST5, ST1, and ST8. Twenty-three genes encoding resistance to 12 antimicrobial classes were observed with blaZ (97%) being the most prevalent. Other predominant resistance genes included tetK (46%), cat (42%), and dfrG (36%) encoding resistance for tetracyclines, phenicols, and diaminopyrimidine, respectively. Virulence genes for enterotoxins, biofilms, toxic-shock-syndrome toxins, hemolysins, and leukotoxins were also detected. Phylogenetic analysis revealed a shift in the dominant clone from MSSA ST152 to MRSA ST152 over the past decade. The study provides valuable insights into the genomic content of S. aureus from clinical sources in Ghana. The finding of ST152 MRSA in high numbers suggests a shifting epidemiological landscape of these pathogens and continuous surveillance using robust tools like WGS is needed to monitor the rise and spread of these epidemic clones in the country.IMPORTANCESince its emergence in 1959, MRSA has been a significant public health concern, causing infections in both clinical and community settings. Patients with MRSA-related infections experience higher mortality rates due to its ability to evade antimicrobials and immune defenses. In Ghana, understanding the molecular epidemiology of MRSA has been hindered by the lack of appropriate laboratory infrastructure and the limited capacity for molecular data analysis. This study, the largest genomic study of S. aureus in Ghana, addresses this gap by utilizing whole genome sequencing to examine the diversity of circulating S. aureus strains from 10 hospitals. Our findings highlight the predominance of pandemic clones, particularly ST152, and the notable transition of ST152 MSSA to ST152 MRSA over the past decade. The findings from this study supports AMR surveillance efforts in Ghana and emphasize the importance of implementing genomic surveillance using WGS to comprehensively monitor the rise and spread of multi-drug-resitant organisms such as MRSA in the country.

Keywords: Africa; ST152 methicillin-resistant S. aureus; whole genome sequencing.

Fig 1

Geographical locations and clinical sources of the 159 S. aureus isolates. ERH, Eastern Regional Hospital; SMDHE, St. Martin De Porres Hospital Eikwe; BRH, Bolgatanga Regional Hospital; 37MH, 37 Military Hospital; ENRH, Effia Nkwanta Regional Hospital; TTH, Tamale Teaching Hospital; LEH, Lekma Hospital; LGH, Legon Hospital; KBTH, Korle-bu Teaching Hospital; SPH, St. Patrick’s Hospital.

Fig 2

(A) Network analysis of the MRSA isolates showing correlation among the resistance genes and sequence types. The size of the nodes is proportional to the number of connections and the thickness of the edges express the strength of the correlations. Sequence types are represented by green nodes, while resistance genes are denoted by pink nodes. (B) Network analysis of the MSSA isolates showing correlation between the resistance genes and sequence types. The size of the nodes is proportional to the number of connections and the thickness of the edges express the strength of the correlations. Sequence types are represented by yellow nodes, while resistance genes are denoted by purple nodes.

Fig 3

Core maximum likelihood phylogeny of the 159 S. aureus isolates. Phylogenetic tree was constructed based on single nucleotide polymorphisms aligned to reference strain NC_007795.1 The Phylogeny was inferred using Realphy. Nine major clusters were obtained (C1 to C9). **, isolates with novel ST. Rings annotated around the tree from the inner to outer; first ring (location), second ring (source), third ring (multi-locus sequence type), fourth ring (MRSA status), fifth ring (PVL status). The number of resistance genes harbored by each isolates is reported on the outermost ring as bar plot.

Fig 4

Single nucleotide polymorphisms-based phylogeny of the ST152 isolates from this study (n = 58) from clinical sources and ST152 isolates from previous Ghanaian studies (n = 24) recovered from clinical sources available at bv-brc.org. Tree was constructed using CSI-phylogeny aligned to reference strain NC_007795.1 and visualized using Interactive Tree of Life (iTOL). IDs highlighted in blue indicate strains from previous studies and those in black indicate strains from the current study. Inner ring shows the year of isolation. Middle ring shows regional location. Outer ring indicates MRSA status. Branches where current and previous strain cluster together are highlighted (Cluster 1 to Cluster 7).