JAC-antimicrobial resistance · 2026
Emergence and dissemination of an IncC plasmid co-harbouring bla KPC-2, bla NDM-1 and bla VIM-24 carbapenemase genes across multiple Gram-negative species in Colombia.
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Sierra Roberto, Castro Betsy, De La Cadena Elsa, Rojas Laura J, García-Betancur Juan Carlos, Roch Mélanie, Marshall Steven M, Bolaño-Ardila Nalleth, Rudin Susan D, Escobar-Arcos Janneth J, Salazar-Montes Clara J, Palacio-Villalba Belkis, Paz Elizabeth, Bonomo Robert A, Villegas María Virginia, Andrey Diego O
Аннотация
OBJECTIVES: Carbapenem-resistant Gram-negative bacilli (CRGNB) pose a public health threat, increasingly driven by plasmid-mediated dissemination of carbapenemase genes. As part of a Colombian genomic monitoring programme, we aimed to characterize CRGNB co-harbouring multiple carbapenemase genes and determine their genetic context.
METHODS: We screened 832 carbapenem-resistant isolates collected during 2011-2023 using carbapenemase-targeted qPCR. Ten isolates co-harbouring bla KPC, bla NDM and bla VIM underwent antimicrobial susceptibility testing, long-read whole-genome sequencing, comparative genomics and conjugation assays.
RESULTS: Nine Enterobacterales isolates and one Aeromonas caviae isolate from unrelated patients in geographically distant Colombian hospitals carried closely related IncC plasmids ranging from 160 to 317 kb. These plasmids co-harboured bla KPC-2, bla NDM-1 and bla VIM-24 within three conserved multidrug resistance regions, including a Tn21-associated region carrying bla NDM-1 and bla VIM-24 and a Tn6454-associated bla KPC-2 platform, alongside class 1 integrons, insertion sequences and multiple additional antimicrobial resistance determinants. The ten isolates were resistant to multiple β-lactam/β-lactamase inhibitor combinations, and five were cefiderocol resistant. Aztreonam/avibactam remained active against all isolates; colistin resistance was confined to intrinsically resistant Providencia rettgeri and Serratia sarumanii. Conjugation assays demonstrated plasmid transfer to Escherichia coli J53, and sequencing confirmed transfer of a 179 kb IncC plasmid with functional conjugation machinery. Comparative genomic analysis showed a highly conserved IncC plasmid backbone across multiple species, supporting broad dissemination of this resistance platform.
CONCLUSIONS: This first report of a single plasmid co-harbouring three carbapenemase genes. This finding highlights a concerning mechanism for interspecies dissemination of MDR Gram-negative pathogens and underscores the importance of long-read genomic surveillance focused on high-risk plasmids.
METHODS: We screened 832 carbapenem-resistant isolates collected during 2011-2023 using carbapenemase-targeted qPCR. Ten isolates co-harbouring bla KPC, bla NDM and bla VIM underwent antimicrobial susceptibility testing, long-read whole-genome sequencing, comparative genomics and conjugation assays.
RESULTS: Nine Enterobacterales isolates and one Aeromonas caviae isolate from unrelated patients in geographically distant Colombian hospitals carried closely related IncC plasmids ranging from 160 to 317 kb. These plasmids co-harboured bla KPC-2, bla NDM-1 and bla VIM-24 within three conserved multidrug resistance regions, including a Tn21-associated region carrying bla NDM-1 and bla VIM-24 and a Tn6454-associated bla KPC-2 platform, alongside class 1 integrons, insertion sequences and multiple additional antimicrobial resistance determinants. The ten isolates were resistant to multiple β-lactam/β-lactamase inhibitor combinations, and five were cefiderocol resistant. Aztreonam/avibactam remained active against all isolates; colistin resistance was confined to intrinsically resistant Providencia rettgeri and Serratia sarumanii. Conjugation assays demonstrated plasmid transfer to Escherichia coli J53, and sequencing confirmed transfer of a 179 kb IncC plasmid with functional conjugation machinery. Comparative genomic analysis showed a highly conserved IncC plasmid backbone across multiple species, supporting broad dissemination of this resistance platform.
CONCLUSIONS: This first report of a single plasmid co-harbouring three carbapenemase genes. This finding highlights a concerning mechanism for interspecies dissemination of MDR Gram-negative pathogens and underscores the importance of long-read genomic surveillance focused on high-risk plasmids.