Genomic Study of Chromosomally and Plasmid-Mediated Multidrug Resistance and Virulence Determinants in Klebsiella Pneumoniae Isolates Obtained from a Tertiary Hospital in Al-Kharj, KSA

Abstract

Klebsiella pneumoniae is an emergent pathogen causing respiratory tract, bloodstream, and urinary tract infections in humans. This study defines the genomic sequence data, genotypic and phenotypic characterization of K. pneumoniae clinically isolated from Al-Kharj, KSA. Whole-genome analysis of four K. pneumoniae strains was performed, including de novo assembly, functional annotation, whole-genome-phylogenetic analysis, antibiotic-resistant gene identification, prophage regions, virulent factor, and pan-genome analysis. The results showed that K6 and K7 strains were MDR and ESBL producers, K16 was an ESBL producer, and K8 was sensitive to all tested drugs except ampicillin. K6 and K7 were identified with sequence type (ST) 23, while K16 and K8 were identified with STs 353 and 592, respectively. K6 and K7 were identified with the K1 (wzi1 genotype) capsule and O1 serotype, while K8 was identified with the K57 (wzi206 genotype) capsule and O3b. K6 isolates harbored 10 antimicrobial resistance genes (ARGs) associated with four different plasmids; the chloramphenicol acetyltransferase (catB3), blaOXA-1 and aac(6′)-Ib-cr genes were detected in plasmid pB-8922_OXA-48. K6 and K7 also carried a similar gene cassette in plasmid pC1K6P0122-2; the gene cassettes were the trimethoprim-resistant gene (dfrA14), integron integrase (IntI1), insertion sequence (IS1), transposase protein, and replication initiation protein (RepE). Two hypervirulent plasmids were reported in isolates K6 and K7 that carried synthesis genes (iucA, iucB, iucC, iucD, and iutA) and iron siderophore genes (iroB, iroC, iroD, and iroN). The presence of these plasmids in high-risk clones suggests their dissemination in our region, which represents a serious health problem.

Prevalence of class A ESBL, class B and D carbapenemase encoding genes (CTX-M, TEM, SHV, NDM, IMP, OXA-48) in gram-negative bacterial pathogens isolated from various clinical samples collected from northern region of United Arab Emirates

“…The lowest co-existence patterns were bla TEM+SHV & bla CTX-M+TEM+SHV represented by K. pneumoniae (6.67%) and E. coli (3.82%) respectively. Similarly, the highest co-existence of the gene bla CTX-M+TEM (21%) was found in the ESBL E. coli & K. pneumoniae from Qatar [59], Saudi Arabia [45, 69] and followed by the least co-existence of the genes bla TEM+SHV, bla CTX-M+SHV & bla CTX-M+TEM+SHV were detected in their same studies, but in contrast, the Moglad et al , Badger-Emeka et al and Sid Ahmed et al found that the highest co-harbored genes were bla CTX-M+TEM+SHV (50% & 24.7%), bla CTX-M+SHV (50% & 10.1%) found in the E. coli , K. pneumoniae and other Enterobacterales in their studies. [70,71] Likewise, the lowest co-expression of the genes bla TEM+NDM , bla TEM+IMP and bla CTX-M+TEM+SHV+IMP were also detected in 2.22% K. pneumoniae, 5% P. aeruginosa and 10% of each A. baumannii to each gene combination.…”

Risk factors in acquiring multidrug-resistant Klebsiella pneumoniae infections in a hospital setting in Saudi Arabia

“…In addition, the horizontal transfer of mobile genetic elements carrying resistant determinants to several antimicrobial types is the major driver of resistance in gram-negative bacteria 24 . Today, more than 100 acquired resistance genes have been identified in Klebsiella strains, conferring the susceptibility of wide ranges of antimicrobial agents 2 , 25 . This corroborates the need to continue molecular epidemiology studies to assess the resistance genotypes and their diversity and distribution in each region 8 .…”

“…This finding is similar to those reported from the eastern region of the country where the proportions of resistance were more than 70% for ampicillin, amoxicillin/clavulanic acid, amoxicillin/clavulanic acid, ceftriaxone and cefuroxime 11 . In addition, a study indicated that K. pneumoniae has become resistant to third-generation cephalosporins and carbapenems, which led to narrowing therapeutic choices for MDR K. pneumoniae infection 2 . The high resistance rates could be explained by these antibiotics being the most prescribed therapeutic agents in clinical settings.…”

“…Klebsiella pneumoniae ( K. pneumoniae ) is a gram-negative bacteria that cause frequent types of nosocomial infections 1 , 2 . Worldwide prevalence of hospital-acquired infections was reported as 8.7%, and about 10% were due to K. pneumoniae 1 .…”

“…Worldwide prevalence of hospital-acquired infections was reported as 8.7%, and about 10% were due to K. pneumoniae 1 . K. pneumoniae carries genes that mediate resistance to multiple antimicrobial drugs and can transfer these genes to other gram-negative bacteria 2 . Moreover, multidrug-resistant (MDR) K. pneumoniae cause different types of infection, including lower respiratory tract infections, bacteremia, bloodstream infections, wound infections and urinary tract infections 3 .…”