Changes in the Clonal Nature and Antibiotic Resistance Profiles of Methicillin-Resistant Staphylococcus aureus Isolates Associated with Spread of the EMRSA-15 Clone in a Tertiary Care Portuguese Hospital

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.

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Prevalence and Characterization of Methicillin-Resistant Staphylococcus aureus from Community- and Hospital-Associated Infections: A Tertiary Care Center Study

Antibiotics ◽

10.3390/antibiotics10020197 ◽

2021 ◽

Vol 10 (2) ◽

pp. 197

Author(s):

Puthiya Purayil Preeja ◽

Sanath H. Kumar ◽

Veena Shetty

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Methicillin Resistant Staphylococcus Aureus ◽

Sccmec Type ◽

Tertiary Care ◽

Diffusion Method ◽

Methicillin Resistant ◽

Type Iv ◽

Type V ◽

Hospital Associated Infections

The community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become increasingly prevalent in both community and hospital settings. The aim of this study was to determine the prevalence, molecular characteristics and antibiotic resistance profiles of CA-MRSA from community- and hospital-associated infections in a tertiary care hospital in Mangalore, India. Of 520 S. aureus isolates, 362 were from inpatients (IP) and 158 were from outpatients (OP). One-hundred and thirty-two MRSA isolates obtained from 94 inpatients and 38 outpatients with complete clinical details were further analyzed. Of these, 81 (61.4%) were CA-MRSA (IP-47.9%, OP-94.7%) and 51 (38.6%) were HA-MRSA (IP-52.1%, OP-5.3%). All (100%) MRSA isolates were mecA gene positive. SCCmec typing identified SCCmec type IV (50.6%) and SCCmec type V (66.7%) in CA-MRSA, while SCCmec type I (41.2%), SCCmec type III (19.6%), SCCmec type IV (31.4%) and SCCmec type V (25.5%) were detected in HA-MRSA isolates. The Panton–Valentine Leukocidin (PVL) gene was found in 70.4% of CA-MRSA, 43.1% of HA-MRSA with SCCmec type IV and SCCmec type V, and in 7.8% of true HA-MRSA. The antibiotic resistance profiles were determined by the disc diffusion method. Resistance to cefoxitin was used to identify MRSA. A significant difference (p < 0.05) was observed between CA-MRSA and HA-MRSA with respect to resistance against cephalexin, cefotaxime, levofloxacin, linezolid and teicoplanin. CA-MRSA was predominantly resistant to ciprofloxacin (86.4%), erythromycin (66.7%), ofloxacin (49.4%), cefotaxime (44.4%), gentamicin (40.7%) and clindamycin (40.7%), while HA-MRSA showed resistance against ciprofloxacin (80.4%), erythromycin (80.1%), cefotaxime (70.6%),ofloxacin (58.8%), clindamycin (47.1%) and levofloxacin (41.2%).This study reports the prevalence of CA-MRSA in community and hospital settings and the possibility of multidrug-resistant CA-MRSA replacing HA-MRSA in hospitals. The observations from our study emphasize the need for urgent measures to manage this emerging crisis in healthcare settings.

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Faculty Opinions recommendation of Novel determinants of antibiotic resistance: identification of mutated loci in highly methicillin-resistant subpopulations of methicillin-resistant Staphylococcus aureus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718344104.793494609 ◽

2014 ◽

Author(s):

Suzanne Walker ◽

Marina Santiago

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistant

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Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates

Pharmaceuticals ◽

10.3390/ph14050420 ◽

2021 ◽

Vol 14 (5) ◽

pp. 420

Author(s):

Tanveer Ali ◽

Abdul Basit ◽

Asad Mustafa Karim ◽

Jung-Hun Lee ◽

Jeong-Ho Jeon ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Active Site ◽

Methicillin Resistant Staphylococcus Aureus ◽

Meca Gene ◽

Resistance Mechanism ◽

Ligand Docking ◽

Clinical Samples ◽

Allosteric Site ◽

Methicillin Resistant

β-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. Staphylococcus aureus acquires resistance against β-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the mecA gene. PBP2a participates in peptidoglycan biosynthesis and exhibits a poor affinity towards β-lactam antibiotics. The current study was performed to determine the diversity and the role of missense mutations of PBP2a in the antibiotic resistance mechanism. The methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical samples were identified using phenotypic and genotypic techniques. The highest frequency (60%, 18 out of 30) of MRSA was observed in wound specimens. Sequence variation analysis of the mecA gene showed four amino acid substitutions (i.e., E239K, E239R, G246E, and E447K). The E239R mutation was found to be novel. The protein-ligand docking results showed that the E239R mutation in the allosteric site of PBP2a induces conformational changes in the active site and, thus, hinders its interaction with cefoxitin. Therefore, the present report indicates that mutation in the allosteric site of PBP2a provides a more closed active site conformation than wide-type PBP2a and then causes the high-level resistance to cefoxitin.

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