Journal Article

Genomic convergence of multidrug resistance, virulence-associated loci, and phage defense systems in Klebsiella pneumoniae from pharmaceutical wastewater in Bangladesh

Sarkar, Md. Murshed Hasan, Mehzabin, Kaniz, Mumtaz, Tabassum, Bhim, Manotush, Ahmed, Md Firoz, Faruk, Mohammad Omar, Hossain, Md. Ismail, Chowdhury, Sanjana Fatema, Naser, Showti Raheel

2026

Overview

Klebsiella pneumoniae strains that combine multidrug resistance and enhanced virulence pose a growing global public health threat. Understanding the genetic basis of these high-risk lineages is critical for surveillance and mitigation. We isolated K. pneumoniae JU-BAEC-01 from treated effluent of antibiotic-manufacturing pharmaceutical facilities in Bangladesh and performed whole-genome sequencing with comparative genomic analyses to characterize its phylogeny, resistome, virulence-associated loci, mobile genetic elements, and predicted antiviral defense systems. JU-BAEC-01 belongs to a phylogenetically distinct lineage, serotype O3b: KL150 with resistance to nearly all clinically relevant antibiotic classes except carbapenems and colistin, mediated by an extensive acquired resistome, including tmexCD3-toprJ3 (tigecycline), armA, aac(6’)-Ib-cr, qnrB4, oqxAB, blaDHA-1, blaSHV-182, and blaTEM-1B, mostly carried on conjugative IncC, IncFIB, IncHI1B, and IncR plasmids. Classical hypervirulence markers are present: complete aerobactin (iucABCD-iutA) and salmochelin (iroBCDEN) clusters, rmpA2, type 1 and type 3 fimbriae, T6SS, and pgaABCD. Notably, the strain encodes one of the most elaborate anti-phage defense arsenals reported in Klebsiella to date, comprising functional Type I-E, III-A, and IV-A CRISPR-Cas systems, multiple restriction-modification systems, BREX Type I, abortive infection systems (AbiE, AbiU), and additional novel defenses that coexist with phage-derived anti-CRISPR (AcrIE9) and anti-restriction (ArdA) proteins. K. pneumoniae  JU-BAEC-01 is a “perfect storm” pathogen that combines multi-drug resistance (MDR), hypervirulence, and a multilayered, highly developed defense against bacteriophages. Together, these findings highlight the environmental emergence of a genetically distinct, multidrug-resistant K. pneumoniae with substantial virulence potential and complex phage–host interaction capacity, underscoring the need for genomic surveillance of pharmaceutical wastewater systems.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326 / 631/337 / Aerobactin / Anti-Bacterial Agents - pharmacology / Antibiotics / Antimicrobial agents / Bacteria / Bacteriophages - genetics / Bangladesh / Carbapenems / Colistin / CRISPR / Drug resistance / Drug Resistance, Multiple, Bacterial - genetics / E coli / Effluent treatment / Effluents / Genome, Bacterial / Genomic analysis / Genomics / Health risks / Humanities and Social Sciences / Humans / Klebsiella pneumoniae / Klebsiella pneumoniae - drug effects / Klebsiella pneumoniae - genetics / Klebsiella pneumoniae - isolation & purification / Klebsiella pneumoniae - pathogenicity / Klebsiella pneumoniae - virology / Manufacturing / Medical wastes / multidisciplinary / Multidrug resistance / Multidrug resistant organisms / Nosocomial infections / Pathogens / Penicillin / Phages / Pharmaceutical industry wastes / Pharmaceuticals / Phylogenetics / Phylogeny / Pili / Plasmids / Public health / Restriction-modification / Science / Science (multidisciplinary) / Taxonomy / Tigecycline / Virulence / Virulence - genetics / Virulence Factors - genetics / Wastewater / Wastewater - microbiology / Wastewater treatment / Whole Genome Sequencing