Investigating the OXA Variants of ESKAPE Pathogens

Abstract

ESKAPE pathogens are the leading cause of nosocomial infections. The Global Priority List of WHO has categorized ESKAPE as priority 1 and 2 pathogens. Even though several mechanisms contribute to antimicrobial resistance, OXA β-lactamase has emerged as a new threat in combating nosocomial infections. In the present study we have investigated the presence of OXA and their variants, copy number, distribution on chromosomes/plasmids, subfamilies, phylogenetic relationships, amino acid identities and variabilities in ESKAPE pathogens. Our results revealed that a total of 929 OXA were present in 2258 completely assembled genomes, which could be further subdivided into 16 sub-families. Among all the ESKAPE pathogens, OXA were highly prevalent in A. baumannii, followed by P. aeruginosa and K. pneumoniae but completely absent in E. faecium and S. aureus while, only a few copies were found in Enterobacter spp. Most of the OXA variants belonged to the OXA-51-like subfamily (200 proteins), followed by OXA-50-like subfamily (189 proteins), OXA-23-like subfamily (156 proteins) and OXA-1-like subfamily (154 proteins). OXA-51-like, OXA-213-like, OXA-134-like, OXA-58-like, OXA-24-like and OXA-20-like subfamilies were present exclusively in A. baumannii. Phylogenetic tree of the subfamilies revealed that OXA-1-like and OXA-33-like, OXA-51-like and OXA-213-like and, OXA-5-like and OXA-10-like belonged to the same branches with amino acid identities as 100%, 97.10% and 80.90% respectively. This indicates that the members of these subfamily-pairs might have evolved from the same ancestor or have recently diverged. Thus, a judicious use of carbapenems is warranted to curtail the rise of new OXA enzymes and preserve them. This is the first detailed report about the OXA of ESKAPE pathogens.

Genomic analyses of Bacteroides fragilis: subdivisions I and II represent distinct species

“…This suggests that OXA AMR genes are not utilized as frequently by B. fragilis to confer resistance to β-lactam antibiotics unlike pathogenic bacteria including Acinetobacter baumannnii , Pseudomonas aeruginosa and Klebsiella pneumoniae, where these genes are found in greater abundance [72, 73].…”

“…Despite being considered as the largest of the β-lactamase families, AMR genes encoding the OXA class-D β-lactamases were relatively scarce among genomes investigated, with two and eight hits being generated for B. fragilis sensu stricto and B. fragilis A, respectively. This suggests that OXA AMR genes are not utilized as frequently by B. fragilis to confer resistance to β-lactam antibiotics unlike pathogenic bacteria including Acinetobacter baumannnii, Pseudomonas aeruginosa and Klebsiella pneumoniae, where these genes are found in greater abundance [72,73].…”

Efficacy and In Vitro Activity of Novel Antibiotics for Infections With Carbapenem-Resistant Gram-Negative Pathogens

“…The spectrum of class D OXA β-lactamases has expanded dramatically in the last years with the addition of several new variants. This class has been detected in chromosomes and plasmids of diverse bacterial species ( Pandey et al., 2021 ).…”

Comparative genomic analysis of plasmids harboring blaOXA-48-like genes in Klebsiella pneumoniae

“…K. pneumoniae is a significant cause of both community- and hospital-acquired infections such as pneumonia, urinary tract infections, bloodstream infections, and septicemia ( Pitout et al., 2015 ; Bengoechea and Sa Pessoa, 2019 ) and is known for its high frequency of antimicrobial resistance (AMR) genes ( Navon-Venezia et al., 2017 ; Wyres and Holt, 2018 ). K. pneumoniae has been classified into one of the ESKAPE pathogens, which are the leading cause of nosocomial infections ( Pandey et al., 2021 ). The emergence and spread of carbapenem-resistant K. pneumoniae (CRKP) have become a severe medical problem worldwide ( Navon-Venezia et al., 2017 ).…”