Emergence of Hypermucoviscous Colistin-Resistant High-Risk Convergent
            <i>Klebsiella Pneumoniae</i>
            ST-2096 Clone From Pakistan

Urooj, Maleeha; Shoukat, Mehreen; Imran, Muhammad; Ansar, Muhammad; Faryal, Rani

doi:10.2217/fmb-2021-0292

Cited by 5 publications

(2 citation statements)

References 40 publications

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“…Consistent with our findings, carbapenemase-carrying plasmids have been shown to occur in diverse lineages and are associated with previously reported high-risk clones that frequently spread across healthcare networks [43]. In addition to the global high-risk clones, our results highlight the significance of ST2096, which appears to be currently limited to Saudi Arabia, the Middle East, and South Asia [16,[44][45][46]. An expanding ST2096 clone was reported in a single-hospital study over an 8-year period in Jeddah and was proposed to be an emerging clone, with pervasive transmission within the hospital wards and links to sepsis and adverse clinical manifestations [16].…”

Section: Discussionsupporting

confidence: 91%

The Dissemination of Multidrug-Resistant and HypervirulentKlebsiella pneumoniaeClones Across the Kingdom of Saudi Arabia

Huang,

Alhejaili,

Alkherd

et al. 2024

Preprint

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The Gram-negative bacterium Klebsiella pneumoniae is a major human health threat underlying a broad range of community- and hospital-associated infections. The emergence of clonal hypervirulent strains often resistant to last-resort antimicrobial agents has become a global burden as treatment options are limited. The Kingdom of Saudi Arabia (KSA) has a dynamic and diverse population and serves as a major global tourist hub facilitating the dissemination of multidrug-resistant (MDR) strains of K. pneumoniae. To examine the spread of clinically relevant Klebsiella pneumoniae strains, we characterized the population structure and dynamics of multidrug-resistant K. pneumoniae across the KSA hospitals. Methods We conducted a large genomic survey on a Saudi Arabian collection of multidrug-resistant K. pneumoniae isolates from bloodstream and urinary tract infections. The isolates were collected from 32 hospitals located in 15 major cities across the country in 2022 and 2023. We subjected 352 K. pneumoniae isolates to whole-genome sequencing and employed a broad range of genomic epidemiological and phylodynamic methods to analyse population structure and dynamics at high resolution. We employed an integrated short- and long-read sequencing approach to fully characterize multiple plasmids carrying resistance and virulence genes. Results Our results indicate that, despite a diverse K. pneumoniae population underlying hospital infections, the population is characterized by the rapid expansion of a few dominant clones, including ST096 (n=115), ST147 (n=75), ST231 (n=35), ST101 (n=30), ST11 (n=18), ST16 (n=15) and ST14 (n=12). ST2096, ST231, and ST147 clones were estimated to have formed within the past two decades and spread between hospitals across the country on an epidemiological time scale. All STs were genetically linked with globally circulating clones, particularly strains from the Middle East and South Asia. All of the major clones harboured plasmid-borne ESBLs and a range of carbapenemase genes. Plasmidome analysis revealed multiple mosaic plasmids with resistance and virulence gene cassettes, some of which were shared between the major clades and account for multidrug resistant hypervirulent (MDR/hv) phenotype, especially in the ST2096 strains. Integration of phylodynamic data and resistance plasmid profiles showed that the acquisition of plasmids occurred on the same time scales as did the expansion of major clones across the country. Conclusion Taken together, these results indicate the dissemination of MDR and MDR-hv K. pneumoniae strains across the kingdom and provide evidence for pervasive plasmid sharing and horizontal gene transfer of resistance genes. The results demonstrate the independent introduction of endemic ST147, ST231, and ST101 clones into the country and highlight the clinical significance of ST2096 as an emerging clone with dual resistance and virulence risks. These results highlight the need for continuous surveillance of circulating and newly emergent strains (STs) and of their plasmidome footprints carrying MDR determinants.

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Section: Discussionsupporting

confidence: 91%

The Dissemination of Multidrug-Resistant and HypervirulentKlebsiella pneumoniaeClones Across the Kingdom of Saudi Arabia

Huang,

Alhejaili,

Alkherd

et al. 2024

Preprint

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“…The genes for type I fimbriae ( fimA-fimK ) and type III fimbriae ( mrkB-mrkJ ) and pili ( ecpA) have established roles in biofilm formation and UTI [ 47 , 49 ] and were present in all the isolates. In addition to fimbriae and pili, we have detected genetic elements like adhesion genes pgaABC and bcsA, luxS in quorum sensing, treC and sugE for capsule production, the combined effect of which have been reported crucial to produce an excellent biofilm [ 50 , 51 ]. Several snps were observed in treC and wza genes in all the isolates as previously reported [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the resistome, virulome, and mobilome of multidrug-resistant Klebsiella pneumoniae isolates: deciphering the molecular basis of carbapenem resistance

Rahmat Ullah,

Irum,

Mahnoor

et al. 2024

BMC Genomics

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Background Klebsiella pneumoniae, a notorious pathogen for causing nosocomial infections has become a major cause of neonatal septicemia, leading to high morbidity and mortality worldwide. This opportunistic bacterium has become highly resistant to antibiotics due to the widespread acquisition of genes encoding a variety of enzymes such as extended-spectrum beta-lactamases (ESBLs) and carbapenemases. We collected Klebsiella pneumoniae isolates from a local tertiary care hospital from February 2019–February 2021. To gain molecular insight into the resistome, virulome, and genetic environment of significant genes of multidrug-resistant K. pneumoniae isolates, we performed the short-read whole-genome sequencing of 10 K. pneumoniae isolates recovered from adult patients, neonates, and hospital tap water samples. Results The draft genomes of the isolates varied in size, ranging from 5.48 to 5.96 Mbp suggesting the genome plasticity of this pathogen. Various genes conferring resistance to different classes of antibiotics e.g., aminoglycosides, quinolones, sulfonamides, tetracycline, and trimethoprim were identified in all sequenced isolates. The highest resistance was observed towards carbapenems, which has been putatively linked to the presence of both class B and class D carbapenemases, blaNDM, and blaOXA, respectively. Moreover, the biocide resistance gene qacEdelta1 was found in 6/10 of the sequenced strains. The sequenced isolates exhibited a broad range of sequence types and capsular types. The significant antibiotic resistance genes (ARGs) were bracketed by a variety of mobile genetic elements (MGEs). Various spontaneous mutations in genes other than the acquired antibiotic-resistance genes were observed, which play an indirect role in making these bugs resistant to antibiotics. Loss or deficiency of outer membrane porins, combined with ESBL production, played a significant role in carbapenem resistance in our sequenced isolates. Phylogenetic analysis revealed that the study isolates exhibited evolutionary relationships with strains from China, India, and the USA suggesting a shared evolutionary history and potential dissemination of similar genes amongst the isolates of different origins. Conclusions This study provides valuable insight into the presence of multiple mechanisms of carbapenem resistance in K. pneumoniae strains including the acquisition of multiple antibiotic-resistance genes through mobile genetic elements. Identification of rich mobilome yielded insightful information regarding the crucial role of insertion sequences, transposons, and integrons in shaping the genome of bacteria for the transmission of various resistance-associated genes. Multi-drug resistant isolates that had the fewest resistance genes exhibited a significant number of mutations. K. pneumoniae isolate from water source displayed comparable antibiotic resistance determinants to clinical isolates and the highest number of virulence-associated genes suggesting the possible interplay of ARGs amongst bacteria from different sources.

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Genomic analysis of extensively drug resistant (XDR) Klebsiella pneumoniae high-risk clone ST14 co-harboring blaNDM and blaOXA-48 recovered from Saudi Arabia

Al-Zahrani,

Aljabri,

Alhazmi

et al. 2024

Journal of Infection and Public Health

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Emergence of Hypermucoviscous Colistin-Resistant High-Risk Convergent Klebsiella Pneumoniae ST-2096 Clone From Pakistan

Cited by 5 publications

References 40 publications

The Dissemination of Multidrug-Resistant and HypervirulentKlebsiella pneumoniaeClones Across the Kingdom of Saudi Arabia

The Dissemination of Multidrug-Resistant and HypervirulentKlebsiella pneumoniaeClones Across the Kingdom of Saudi Arabia

Exploring the resistome, virulome, and mobilome of multidrug-resistant Klebsiella pneumoniae isolates: deciphering the molecular basis of carbapenem resistance

Genomic analysis of extensively drug resistant (XDR) Klebsiella pneumoniae high-risk clone ST14 co-harboring blaNDM and blaOXA-48 recovered from Saudi Arabia

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