Genomic Investigation of Methicillin-Resistant Staphylococcus aureus ST113 Strains Isolated from Tertiary Care Hospitals in Pakistan.

Nimat Ullah,Kanwal Naz,Abdur Rahman,Saadia Andleeb,Taeok Bae,Fazal Hanan,Muhammad Tariq Saeed,Hamza Arshad Dar,Amjad Ali

doi:10.3390/antibiotics10091121

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a multi-drug resistant and opportunistic pathogen. The emergence of new clones of MRSA in both healthcare settings and the community warrants serious attention and epidemiological surveillance. However, epidemiological data of MRSA isolates from Pakistan are limited. We performed a whole-genome-based comparative analysis of two (P10 and R46) MRSA strains isolated from two provinces of Pakistan to understand the genetic diversity, sequence type (ST), and distribution of virulence and antibiotic-resistance genes. The strains belong to ST113 and harbor the SCCmec type IV encoding mecA gene. Both the strains contain two plasmids, and three and two complete prophage sequences are present in P10 and R46, respectively. The specific antibiotic resistance determinants in P10 include two aminoglycoside-resistance genes, aph(3’)-IIIa and aad(6), a streptothrin-resistance gene sat-4, a tetracycline-resistance gene tet(K), a mupirocin-resistance gene mupA, a point mutation in fusA conferring resistance to fusidic acid, and in strain R46 a specific plasmid associated gene ant(4’)-Ib. The strains harbor many virulence factors common to MRSA. However, no Panton-Valentine leucocidin (lukF-PV/lukS-PV) or toxic shock syndrome toxin (tsst) genes were detected in any of the genomes. The phylogenetic relationship of P10 and R46 with other prevailing MRSA strains suggests that ST113 strains are closely related to ST8 strains and ST113 strains are a single-locus variant of ST8. These findings provide important information concerning the emerging MRSA clone ST113 in Pakistan and the sequenced strains can be used as reference strains for the comparative genomic analysis of other MRSA strains in Pakistan and ST113 strains globally.

Highlights

IntroductionThe pathogenicity and versatility of methicillin-resistant S. aureus (MRSA) to evade the host immune responses can be attributed to its ability to express multiple virulence factors, including enterotoxins, toxic shock syndrome toxin, nucleases, proteases, hemolysins, leucocidins, and fibronectin-binding proteins [7]
SNP phylogenetic tree grouped ST113 strains P10 and R46 close to strains M51 ST1516 (CP030137.1), SVH7513 ST612 (CP029166.1), and 2395 USA500 ST8 (CP007499.1) (Figure 3). This suggests that ST113 strains are closely related to ST8 strains, and on close observation we found that ST113 is a single-locus variant of ST8
The methicillin-resistant S. aureus (MRSA) strains P10 and R46 isolated from Pakistan belong to ST113 and harbor

Summary

Introduction

The pathogenicity and versatility of methicillin-resistant S. aureus (MRSA) to evade the host immune responses can be attributed to its ability to express multiple virulence factors, including enterotoxins, toxic shock syndrome toxin, nucleases, proteases, hemolysins, leucocidins, and fibronectin-binding proteins [7]. These virulence factors are mostly involved in adherence, colonization, and invasion abilities, allowing S. aureus to avoid host immune defense and to promote pathogenicity [8]. The presence of these virulent factors makes

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