Comparative Analysis of Clinical and Genomic Characteristics of Hypervirulent Klebsiella pneumoniae from Hospital and Community Settings: Experience from a Tertiary Healthcare Center in India

Raj, Stephen M.L.; Sharma, Tanya; Pradhan, Dibyabhaba; Tyagi, Sonu; Gautam, Hitender; Singh, Harpreet; Sood, Seema; Dhawan, Benu; Das, Bimal Kumar; Kapil, Arti; Chaudhry, Rama; Mohapatra, Sarita

doi:10.1128/spectrum.00376-22

Cited by 9 publications

(9 citation statements)

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“…This observation suggests multiple instances of the strains being introduced inside and outside Saudi Arabia, indicating the rapid dissemination of these strains and highlighting the global clinical significance of ST2096. Moreover, ST2096, with its similar resistance and virulence characteristics, has been recently reported as a cause of hospital outbreaks in Turkey [ 60 ] and isolated from both community and clinical settings in India [ 15 , 24 ]. The phylodynamic of the total global ST2096 isolates shows that on five occasions, as shown in the phylodynamic tree, samples from Saudi Arabia appear to serve as ancestors to those from Turkey (Figure S 5).…”

Section: Resultsmentioning

confidence: 99%

“…The evolution of ST2096 may also take place beyond hospitals. A recent genomic survey of a smaller collection of ST2096 in India demonstrated the prevalence of these strains not only in clinical settings but also in the community [ 24 ]. In line with this, we detected three strains with confirmed community-acquired infections.…”

Section: Discussionmentioning

confidence: 99%

“…A study in India of blood samples between 2016 and 2017 identified ST231, ST14, and ST2096 as the most prevalent sequence types associated with colistin resistance [ 12 ]. Another study in India indicated the presence of the multidrug-resistant hypervirulent ST2096 strains in the hospital and community in India [ 24 ]. ST2096 strains were also reported in other collections from South Asia and showed genomic signatures of the convergence of resistance and virulence for the strains [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years

Hala,

Malaikah,

Huang

et al. 2024

Genome Med

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Background Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks. Methods In this study, we conducted an in-depth genomic analysis on a large-scale collection of 328 multidrug-resistant (MDR) K. pneumoniae strains recovered from 239 patients from a single major hospital in the western coastal city of Jeddah in Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the predominant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains. Results We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against colistin and extended spectrum β-lactamase (ESBL) and carbapenemase genes, namely blaOXA-48 and blaOXA-232, located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a high virulence level with the presence of the siderophore aerobactin (iuc) locus situated on the same mosaic plasmid as the ESBL gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality (p-value < 0.05). Conclusions Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years

Hala,

Malaikah,

Huang

et al. 2024

Genome Med

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“…Here, we investigate the differences in the epigenetic signatures between hvKp and cKp. Genomic DNA isolated from five cKp and six hvKp clinical isolates ( 3 ) was used to perform native DNA whole-genome sequencing (WGS) using Oxford Nanopore MinION. The six hvKp isolates, identified using string test and PCR for iucA gene, were previously characterized for antimicrobial resistance genes and hypervirulence genes by WGS ( 3 ).…”

Section: Observationmentioning

confidence: 99%

“…Genomic DNA isolated from five cKp and six hvKp clinical isolates ( 3 ) was used to perform native DNA whole-genome sequencing (WGS) using Oxford Nanopore MinION. The six hvKp isolates, identified using string test and PCR for iucA gene, were previously characterized for antimicrobial resistance genes and hypervirulence genes by WGS ( 3 ). Assessment of growth under laboratory conditions showed no significant difference between the cKp and hvKp isolates studied here ( Fig.…”

Section: Observationmentioning

confidence: 99%

Distinct epigenetic signatures of classical and hypervirulent Klebsiella pneumoniae

Ghosh,

Pal,

Mohapatra

et al. 2024

mSphere

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Emergence and spread of the hypervirulent pathotype of Klebsiella pneumoniae have significantly increased infection rates in community as well as healthcare settings. There is an increasing interest to identify discriminating features between classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp) to facilitate our understanding of the rapid emergence and dissemination of the hypervirulent pathotype. Here, we sought to identify unique epigenetic signatures of hvKp pathotype that differ from its classical counterpart using single-base resolution methylome analysis of native DNA sequencing on the Oxford Nanopore Technologies platform. The overall global adenine methylation in GATC motifs (i.e., Dam methylation motif) and cytosine methylation in CCWGG motifs (i.e., Dcm methylation motif) were significantly higher in hvKp isolates compared to that in cKp isolates, irrespective of their position in chromosomes or putative extra-chromosomal genetic elements. Notably, we observed significant enrichment of hypermethylated GATC and CCWGG motifs in the virulome of hvKp compared to hvKp genes not directly associated with virulence. We also observed increased methylation of GATC and CCWGG motifs in the capsule synthesis locus of hvKp isolates compared to cKp isolates. Furthermore, we identified several differentially methylated genes (DMGs) between the two pathotypes; interestingly, these DMGs include metal ion transporters, multidrug efflux pumps, transcriptional regulators of stress response, and genes associated with biofilm formation. Our results highlight hypermethylation of GATC and CCWGG motifs as unique epigenetic signatures of hvKp isolates. IMPORTANCE Hypervirulent Klebsiella pneumoniae (hvKp) is a more virulent and rapidly evolving hypermucoviscous pathotype of classical K. pneumoniae (cKp). The hypervirulent pathotype is a major public health concern and is associated with high infection rates in community as well as hospital settings. With the recent emergence of multidrug-resistant hvKp, it has become imperative to investigate non-classical mechanisms such as epigenetics in addition to canonical biochemical and genetic mechanisms that delineate and differentiate the hypervirulent pathotype from its classical counterpart. Here, we identify genome-wide differences in adenine and cytosine methylation marks at well-characterized motifs between the two pathotypes. Overall, significantly higher levels of methylation were observed across chromosomal DNA and extrachromosomal elements in hvKp compared to cKp. Among hvKp isolates, the genes associated with virulence are particularly enriched for methylation marks. Our findings shed light on how epigenetic signatures may help distinguish the pathogenic potential of bacteria.

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Genotypic characterization of hypervirulent Klebsiella pneumoniae (hvKp) in a tertiary care Indian hospital

Behera,

Swain,

Rout

et al. 2024

Int Microbiol

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Comparative Analysis of Clinical and Genomic Characteristics of Hypervirulent Klebsiella pneumoniae from Hospital and Community Settings: Experience from a Tertiary Healthcare Center in India

Abstract: To date, studies comparing the genomic characteristics of hospital- and community-acquired hvKp were very few in India. In this study, we analyzed the clinical and genomic characteristics of hvKp isolates from hospital and community settings.

Cited by 9 publications

References 46 publications

The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years

The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years

Distinct epigenetic signatures of classical and hypervirulent Klebsiella pneumoniae

Genotypic characterization of hypervirulent Klebsiella pneumoniae (hvKp) in a tertiary care Indian hospital

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