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<p><i>Klebsiella pneumoniae</i> 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 <i>K. pneumoniae</i> 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 <i>Klebsiella</i> 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. <i>K. pneumoniae</i>&#xa0;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 <i>K. pneumoniae</i> with substantial virulence potential and complex phage–host interaction capacity, underscoring the need for genomic surveillance of pharmaceutical wastewater systems.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月23日

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

摘要

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.