Abstract
Carbapenem-resistant P. aeruginosa has become a major clinical problem due to limited treatment options. However, studies assessing the trends in the molecular epidemiology and mechanisms of antibiotic resistance in this pathogen are lacking in Saudi Arabia. Here, we reported the genome characterization in a global context of carbapenem non-susceptible clinical isolates from a nationally representative survey. The antibiotic resistance profiles of the isolates (n = 635) collected over 14 months between March 2018 and April 2019 from different geographical regions of Saudi Arabia showed resistance rates to relevant β-lactams, aminoglycosides and quinolones ranging between 6.93 and 27.56%. Overall, 22.52% (143/635) of the isolates exhibited resistance to both imipenem and meropenem that were mainly explained by porin loss and efflux overexpression. However, 18.18% of resistant isolates harbored genes encoding GES (69.23%), VIM (23.07%), NDM (3.85%) or OXA-48-like (3.85%) carbapenemases. Most common GES-positive isolates produced GESs −5, −15 or −1 and all belonged to ST235 whereas the VIM-positive isolates produced mainly VIM-2 and belonged to ST233 or ST257. GES and VIM producers were detected at different sampling periods and in different surveyed regions. Interestingly, a genome-wide comparison revealed that the GES-positive ST235 and VIM-2-positive ST233 genomes sequenced in this study and those available through public databases from various locations worldwide, constituted each a phylogenetically closely related sub-lineage. Profiles of virulence determinants, antimicrobial resistance genes and associated mobile elements confirmed relatedness within each of these two different sub-lineages. Sequence analysis located the blaGES gene in nearly all studied genomes (95.4%) in the same integrative conjugative element that also harbored the acc(6′)-Ib, aph(3′)-XV, aadA6, sul1, tet(G), and catB resistance genes while blaVIM–2 in most (98.89%) ST233-positive genomes was co-located with aac(6′)-I1, dfrB-5, and aac(3′)-Id in the same class I integron. The study findings revealed the global spread of GES-5 ST235 and VIM-2 ST233 sub-lineages and highlighted the importance of routine detection of rare β-lactamases.
Highlights
P. aeruginosa is a major cause of healthcare associated infections and a serious public health threat due to its ability to resist antibiotics (Gellatly and Hancock, 2013)
P. aeruginosa clinical isolates were referred over a 14-month period from five hospitals located in the eastern, western and central regions of Saudi Arabia
Susceptibility testing showed that 143/635 (22.52%) isolates were resistant to both imipenem and meropenem (MIC ≥ 8 mg/L) (Table 1)
Summary
P. aeruginosa is a major cause of healthcare associated infections and a serious public health threat due to its ability to resist antibiotics (Gellatly and Hancock, 2013). Resistance to carbapenems in the species is due primarily to chromosomal modifications that inactivate or downregulate the carbapenem-specific OprD porin or modify the expression levels of efflux systems and in particular the MexABOprM pump (López-Causapé et al, 2018). In recent years, this pathogen has been increasingly reported as a carrier of acquired carbapenemases and in particular those belonging to the VIM, IMP and GES families (Yoon and Jeong, 2021). ST235 is certainly the most relevant high-risk clone, showing a worldwide dissemination and an association with various β-lactamases, including GES, IMP, KPC, OXA-48, and VIM carbapenemases (Treepong et al, 2018; del Barrio-Tofiño et al, 2020). A genome-wide comparison revealed that these two sub-lineages were disseminated worldwide
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
