Comparative genomics and antibiotic – resistance determinants of clinical pseudomonas aeruginosa isolates from Kenya

Abstract

Pseudomonas aeruginosa is a leading cause of nosocomial infections worldwide. It causes a range of debilitating infections, have a propensity for developing antimicrobial resistance, and present with a variety of dangerous virulence factors. This study investigated the core and accessory genome, the sequence types, phenotypic antimicrobial susceptibility profiles, and resistance and virulence genes among clinical sample isolates from urinary tract, and skin and soft tissue infections. Fifty-six P. aeruginosa clinical sample isolates were obtained from six medical centers across five counties in Kenya between 2015 and 2020. Whole-genome sequencing of the isolates was performed to conduct genomic characterization, sequence typing, and phylogenetic analysis. Results showed a core genome of 1288 genes, including insertion sequences and constitutive resistance and virulence genes. The average accessory genome was 7005 genes, which included genomes of numerous phages, non-constitutive resistance and virulence genes, and only one plasmid (Col(pWES)_1). We also showed the presence of globally distributed high-risk clones (ST244 and ST357), local high-risk clones (ST2025, ST455, and ST233), and a novel multidrug-resistant (MDR) clone carrying virulence genes (ST3674). Furthermore, 31% of the study isolates were found to be MDR with phenotypic resistance to a variety of antibiotics, including piperacillin (79%), ticarcillin-clavulanic acid (57%), meropenem (34%), levofloxacin (70%), and cefepime (32%). Several resistance genes were identified, including carbapenemases VIM-6 (ST1203) and NDM-1 (ST357), fluoroquinolone genes, crpP, and qnrVCi, while 14 and 22 different chromosomal mutations were detected in the gyrA and parC genes, respectively. All isolates contained at least three virulence genes. Among the virulence genes identified, phzB1 was the most abundant (50/56, 89%). 21% (12/56) of the isolates had the exoU+/exoS- genotype, while 73% (41/56) of the isolates had the exoS+/exoU- genotype. This study also discovered twelve novel lineages of P. aeruginosa, of which one (ST3674) demonstrated both extensive antimicrobial resistance and the highest number of virulence genes (236/242, 98%). Although most were uncovered from Nairobi County, high-risk clones were found throughout the country, indicating the local spread of global epidemic clones and the emergence of new strains. Thus, this study illustrates the urgent need for coordinated local, regional, and international antimicrobial resistance surveillance efforts.