The Co-occurrence of NDM-5, MCR-1, and FosA3-Encoding Plasmids Contributed to the Generation of Extensively Drug-Resistant Klebsiella pneumoniae

Abstract

The rise and global dissemination of extensively drug-resistant (XDR) bacteria are often related to plasmid-borne mobile antimicrobial resistance genes. Notably, isolates having multiple plasmids are often highly resistant to almost all the antibiotics available. In this study, we characterized an extensively drug-resistant Klebsiella pneumoniae 1678, which exhibited high-level resistance to almost all the available antibiotics. Through whole-genome sequencing (WGS), more than 20 resistant elements and 5 resistant plasmids were observed. Notably, the tigecycline resistance of K. pneumoniae 1678 was not related to the plasmid-borne tetA gene but associated with the overexpression of AcrAB and OqxAB efflux pumps, according to the susceptibility results of tetA-transformant and the related mRNA quantification of RND efflux pumps. Except for tigecycline resistance, three plasmids, mediating resistance to colistin, Fosfomycin, and ceftazidime–avibactam, respectively, were focused. Detailed comparative genetic analysis showed that all these plasmids belonged to dominated epidemic plasmids, and harbored completed conjugation systems. Results of conjugation assay indicated that these three plasmids not only could transfer to E. coli J53 with high conjugation frequencies, respectively, but also could co-transfer to E. coli J53 effectively, which was additionally confirmed by the S1-PFGE plasmids profile. Moreover, multiple insertion sequences (IS) and transposons (Tn) were also found surrounding the vital resistant genes, which may form several novel mechanisms involved in the resistant determinants’ mobilization. Overall, we characterized and reported the uncommon co-existence and co-transferring of FosA3-, NDM-5, and MCR-1-encoding plasmids in a K. pneumoniae isolate, which may increase the risk of spread of these resistant phenotypes and needing great concern.

Epidemiology, antimicrobial resistance profile and management of Carbapenem-resistant Klebsiella pneumoniae among mothers with suspected sepsis in Ethiopia

“…Those who frequently consumed alcohol, such as beer and tela, and were infected with K. pneumoniae had a greater likelihood of developing severe symptoms, accounting for 42.9% of the patients. These ndings are consistent with many related studies [1,3,6,16,17,34,36,39].The maternal sepsis incidence and treatment of K. pneumoniae vary by region. This could be due to different factors such as sample type, geographic location, patient demographics, immune status, and co-infections, can affect the magnitude and strain type of this bacterium, which is consistent with our ndings in ve tertiary hospitals [10,15,24,35,37].…”

“…Carbapenem-resistant Klebsiella pneumoniae (CRKP) constitute a signi cant concern, and urgent attention is needed to reduce maternal and neonatal sepsis [35,38]. Recent studies indicate that Klebsiella is responsible for 65.7% of antibiotic-resistant bacteria that cause healthcare-associated infections [39,40]. Among these bacteria, half are ESBL-producing K. pneumoniae isolates.…”

Characterization of Hypervirulent and Carbapenem-Resistant K. pneumoniae Isolated from Neurological Patients

“…The genomic DNA of these hv-CRKP was extracted using a commercial DNA extraction kit (Qiagen, Germany) and the genome sequencing was then performed by the Illumina NovaSeq 6000 platform. 16 The multilocus sequence typing (MLST), serotype, resistance and virulence determinants were determined by the Kleborate (version 0.3.0) ( https://github.com/katholt/Kleborate/ ). Plasmid replicons were identified using the PlasmidFinder database using the minimum coverage and minimum identities of 90% ( https://cge.cbs.dtu.dk/services/PlasmidFinder/ ).…”

Fosfomycin resistance mechanisms in Enterobacterales: an increasing threat

“…Additionally, the authors highlighted a clonal relation between KPC- and FosA3-producers, indicating a FOS R clonal dissemination in China ( Jiang et al., 2017 ). In K. pneumoniae plasmid-mediated fosA3 is largely associated with isolates belonging to ST 11 ( Xiang et al., 2015 ; Nishida et al., 2020 ), ST37 ( Taniguchi et al., 2017 ), ST485 ( Zhou et al., 2022 ). In recent years, a secondary spread of plasmid-mediated fosA3 occurred in Salmonella spp.…”