The Dissemination and Molecular Characterization of Clonal Complex 361 (CC361) Methicillin-Resistant Staphylococcus aureus (MRSA) in Kuwait Hospitals

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) belonging to clonal complex 361 (CC361-MRSA) is rare among patients’ populations globally. However, CC361-MRSA has been isolated with an increasing trend among patients in Kuwait hospitals since 2010. This study investigated the molecular characteristics of CC361-MRSA isolated from patients in Kuwait hospitals in 2016–2018 to understand their genetic relatedness and virulence determinants. Of 5,223 MRSA isolates investigated by DNA microarray, 182 (3.4%) isolates obtained in 2016 (N = 55), 2017 (N = 56), and 2018 (N = 71) were identified as CC361-MRSA. The CC361-MRSA isolates were analyzed further using antibiogram, spa typing and multi locus sequence typing (MLST). Most of the isolates were resistant to fusidic acid (64.8%), kanamycin (43.4%), erythromycin (36.3%), and clindamycin (14.3%) encoded by fusC, aphA3, and erm(B)/erm(C) respectively. Nine isolates (4.9%) were resistant to linezolid mediated by cfr. The isolates belonged to 22 spa types with t3841 (N = 113), t315 (N = 16), t1309 (N = 14), and t3175 (N = 5) constituting 81.3% of the spa types, four genotypes (strain types), CC361-MRSA-[V/VT + fus] (N = 112), CC361-MRSA-IV, WA MRSA-29 (N = 36), CC361-MRSA-V, WA MRSA-70/110 (N = 33) and CC361-MRSA-[V + fus] variant (N = 1). MLST conducted on 69 representative isolates yielded two sequence types: ST361 (11/69) and ST672 (58/69). All CC361-MRSA isolates were positive for cap8, agr1, and the enterotoxin egc gene cluster (seg, sei, selm, seln, selo, and selu). The tst1 was detected in 19 isolates. The immune evasion cluster (IEC) genes type B (scn, chp, and sak) and type E (scn and sak) were detected in 20 and 152 isolates, respectively. The CC361-MRSA circulating in Kuwait hospitals consisted of two closely related sequence types, ST361 and ST672 with ST672-MRSA [V/VT + fus] as the dominant genotype. The dissemination of these newly emerged clones and the emergence of linezolid resistance limits therapeutic options, as well as present significant challenges for the control of MRSA infections in Kuwait hospitals.

Diversity and Dissemination of Methicillin-Resistant Staphylococcus aureus (MRSA) Genotypes in Southeast Asia

“…PVL genes were detected in 35.4% of the MRSA isolates, where the majority belonged to ST772-V and ST361-V. Although ST361 is a rare MRSA clone, it has recently expanded steadily in the Arabian Gulf region, demonstrating its ability to disseminate [107]. Meanwhile, most MRSAs that lacked PVL genes belonged to the classic Asian MRSA clone, ST239-III, which was multidrug-resistant.…”

Molecular characterization of typing and subtyping of Staphylococcal cassette chromosome SCCmec types I to V in methicillin-resistant Staphylococcus aureus from clinical isolates from COVID-19 patients

“…It often complicates influenza with a death toll significantly surpassing those of many past pandemics. S. aureus owes its pathogenicity to a series of necrotizing exotoxins that induce a marked neutrophil response resulting in suppurative tissue necrosis ( 4 – 7 ). Particularly potent is a strain of MRSA that secretes an exotoxin known as Panton–Valentine leucocidin (PVL) as well as complicating influenza, this strain has resulted in fatal septic shock in previously healthy persons ( 8 , 9 ).…”

“…SCC mec genomic island comprises two site-specific recombinase genes namely ccrA and ccrB [cassette chromosome recombinase] accountable for mobility. Currently, SCC mec elements are classified into types I, II, III, IV and V based on the nature of the mec and ccr gene complexes and are further classified into subtypes according to variances in their J region DNA ( 5 – 7 ). SSC mec type IV has been found in community-acquired isolates with various genetic backgrounds.…”

“…SCC mec typing technique is an effective guideline to detect and control the dissemination of MRSA ( 4 , 6 ). Multiplex PCR, Multilocus Sequence typing, Antimicrobial susceptibility tests, DNA Microarrays are effectively utilized for the identification MRSA types and subtypes ( 4 , 6 , 7 ).There are very few reports available on characterization of the types of SCC mec types and subtypes I, II, III, IVa, b, c, d, and V and PVL genes among clinical MRSA isolates from India and Asian countries as well.…”

Whole‐genome sequence analysis of Staphylococcus aureus from retail fish acknowledged the incidence of highly virulent ST672‐MRSA‐IVa/t1309, an emerging Indian clone, in Assam, India

“…For instance, draft‐genome of ST672‐MRSA from clinical cases such as sepsis (Bakthavatchalam et al ., 2017), ocular infection (Velusamy et al ., 2014) and septicaemia (Khedkar et al ., 2012) has been reported previously from different parts of India. Further, large‐scale hospital surveillance in Kuwait revealed a high prevalence of ST361 and ST672 MRSA carrying immune evasion clusters (IEC) and staphylococcal enterotoxins (SEs) as virulence factors, and fusC , aphA3 and erm ( B ) /erm ( C ) loci, conferring resistance to fusidic acid, kanamycin and erythromycin respectively (Sarkhoo et al ., 2021). Another study again from the Kuwait hospitals reported the incidence of ST672‐MSSA with reduced susceptibility to chlorhexidine (Vali et al ., 2017).…”