Hackensack Meridian: CRISPR-Cas, anti-CRISPR proteins, and AMR genes in MDR Klebsiella pneumoniae’s success

Research in Barry Kreiswirth’s lab at the Center for Discovery & Innovation, Hackensack Meridian Health, focuses on unraveling the molecular epidemiology of carbapenem-resistant Enterobacteriaceae.  Klebsiella pneumoniae is a pathogen responsible for a range of infections (blood, abdominal, respiratory, urinary tract, etc.), with the CG147 clone being a globally successful multi-drug resistant (MDR) clone that has disseminated worldwide and is linked to various carbapenemases.  Horizontal gene transfer of mobile genetic elements and CRISPR-Cas systems play a role in developing and spreading globally successful K. pneumoniae clones.  Almost all CG147 strains harbor a chromosomal type I-E CRISPR-Cas system, and over 40% also have a plasmid-borne type IV-A3 CRISPR-Cas system, both of which target IncF plasmids that harbor carbapenemase.  The presence of the IV-A3 CRISPR-Cas system is negatively correlated with carbapenemases, while the anti-CRISPR proteins AcrIE8.1 and AcrIE9.2 are positively correlated with carbapenemases.  The success of the globally successful multi-drug resistant Klebsiella pneumoniae clone CG147 is driven by a complex interplay between its CRISPR-Cas immunity systems, acquisition of anti-CRISPR mechanisms, and adaptation to antimicrobial resistance plasmids.

A proposed model depicting the interactions between CRISPR-Cas systems, anti-CRISPR protein, and AMR plasmids in CG147. Chromosomal type I-E CRISPR-Cas confers immunity to AMR plasmid harboring the protospacer; prophage or plasmid borne anti-CRISPR protein hinder the function of CRISPR-Cas system; plasmid borne type IV-A3 CRISPR-Cas provides additional immunity against AMR plasmid; and AMR plasmid lacking CRISPR-Cas protospacer remain unaffected and can persist within the bacterial host

Jiang J, Cienfuegos-Galletd AV, Long T, Peirano G, Chu T, Pitout JDD, Kreiswirth BN, Chen L. Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone. Genome Med. 2025 Jan 30;17(1):9. doi: 10.1186/s13073-025-01428-6. PMID: 39885543; PMCID: PMC11781037.  https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-025-01428-6