Evidence map›Paper›PMID 39885543›Full record

ArticleGenome medicine2025

Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone.

Jianping Jiang, Astrid V Cienfuegos-Gallet, Tengfei Long, Gisele Peirano, Tingyu Chu, Johann D D Pitout, Barry N Kreiswirth, Liang Chen

Erratum issuedAbstract read
In one paragraph

Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

  1. Article
  2. Article
  3. Virulence and Invasion Profiles ofPathogens (Basel, Switzerland) · 2026
    Article
  4. The genomic landscape of Klebsiella pneumoniae in Russia.World journal of microbiology & biotechnology · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Lineage-specific evolution and resistance-virulence divergence inAntimicrobial agents and chemotherapy · 2025
    Article
  10. Review
  11. Antibiotic-ResistantMicroorganisms · 2025
    Review
  12. Article
  13. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Jianping Jiang *Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
Astrid V Cienfuegos-Gallet *Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
Tengfei Long *Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
Gisele Peirano *Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
Tingyu ChuCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
Johann D D PitoutCummings School of Medicine, University of Calgary, Calgary, AB, Canada.
Barry N KreiswirthCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA. barry.kreiswirth@hmh-cdi.org.
Liang ChenCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA. liangch@buffalo.edu.ORCID 0000-0001-5845-2235

Funding

The molecular basis of the epidemic blaKPC gene KlebsiellaR01AI090155 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI KREISWIRTH, BARRY NEAL · 2011 to 2021
$7.2M
NIAID NIH HHS R01 AI090155
6 · The paper itself

Abstract

backgroundKlebsiella pneumoniae is one of the most prevalent pathogens responsible for multiple infections in healthcare settings and the community. K. pneumoniae CG147, primarily including ST147 (the founder ST), ST273, and ST392, is one of the most globally successful MDR clone linked to various carbapenemases.

methodsOne hundred and one CG147 strains were sequenced and additional 911 publicly available CG147 genome sequences were included for analysis. The molecular epidemiology, population structure, and time phylogeny were investigated. The virulome, resistome, and mobilome were analyzed, and the recombination in the capsular region was studied. The CRISPR-Cas and anti-CRISPR were identified. The interplay between CRISPR-Cas, anti-CRISPR, and carbapenemase-encoding plasmids was analyzed and experimentally validated.

resultsWe analyzed 1012 global CG147 genomes, with 80.4% encoding at least one carbapenemase (NDM [529/1012, 52.3%], OXA-48-like [182/1012, 17.7%], and KPC [105/1012, 10.4%]). Surprisingly, almost all CG147 strains (99.7%, 1009/1,012) harbor a chromosomal type I-E CRISPR-Cas system, with 41.8% (423/1012) containing an additional plasmid-borne type IV-A3 CRISPR-Cas system, and both target IncF plasmids, e.g., the most prevalent KPC-encoding pKpQIL-like plasmids. We found the presence of IV-A3 CRISPR-Cas system showed a negative correlation with the presence of KPC. Interestingly, a prophage-encoding anti-CRISPR AcrIE8.1 and a plasmid-borne anti-CRISPR AcrIE9.2 were detected in 40.1% (406/1012) and 54.2% (548/1012) of strains, respectively, which displayed positive correlations with the presence of a carbapenemase. Plasmid transfer experiments confirmed that the I-E and IV-A3 CRISPR-Cas systems significantly decreased (p < 0.001) KPC-encoding pKpQIL plasmid conjugation frequencies, while the AcrIE8.1 and AcrIE9.2 significantly increased (p < 0.001) pKpQIL conjugation frequencies and protected plasmids from elimination by CRISPR-Cas I-E system.

conclusionsOur results indicated a complex interplay between CRISPR-Cas, anti-CRISPR, and mobile genetic elements that shape the evolution of CG147. Our findings advance the understanding of multi-drug resistance mechanisms and will aid in preventing the emergence of future MDR clones.

Indexed as

CRISPR-Cas SystemsDrug Resistance, Multiple, BacterialKlebsiella pneumoniaeAnti-Bacterial AgentsBacterial Proteinsbeta-LactamasesGenome, BacterialHumansKlebsiella InfectionsPhylogenyPlasmidsAnti-Bacterial AgentsBacterial Proteinsbeta-LactamasescarbapenemaseAnti-CRISPRCG147CRISPR-CasGenomic epidemiologyKlebsiella pneumoniae

Identifiers

PMID39885543
PMCPMC11781037

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.