Standardized numbering and alignment of the KPC family of β-lactamases
Abstract
The KPC family of serine β-lactamases comprises more than 260 members. Some variants are associated with ceftazidime-avibactam resistance in clinical isolates, often linked to substitutions and/or insertions/deletions (i.e., INDELs) in three distinct loops of the KPC sequence: (i) the 164–179 loop (i.e., the Ω loop); (ii) the 237–243 loop; and (iii) the 267–275 loop. Inconsistencies in residue numbering across published reports, however, complicate the accurate annotation of KPC variants. We retrieved 267 KPC variant sequences from the Beta-Lactamase Database (BLDB) in September 2025 and analyzed sequence differences between variants using combined nucleotide and structure-guided alignment algorithms, supported by AlphaFold3 modeling in ambiguous cases. Variants were classified into four groups to comprehensively review sequence changes across the KPC family: substitutions only ( n = 126), deletions only ( n = 17), insertions only ( n = 66), and variants with two or more types of amino acid changes ( n = 57). Comparisons with previous reports indicate that many annotation errors stem from overlooking the absent residues 58 and 253 in the KPC consensus sequence, and that most inconsistencies in annotation and residue assignment occur in INDEL variants. To address these issues, we propose a standardized annotation scheme for substitutions, deletions, and insertions for the KPC family, based on the Ambler numbering system, and supported by structural information. This systematic scheme will help to standardize the description of newly emerging KPC variants and prevent discrepancies in future reports in the context of antimicrobial resistance.
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BibTeX
@article{brunetti2026standardized,
title = {{Standardized numbering and alignment of the KPC family of β-lactamases}},
author = {Florencia Brunetti and Steven Marshall and Christopher Bethel and Andrea Hujer and Kristine Hujer and Shozeb Haider and Karen Bush and Patricia Bradford and Barry Kreiswirth and James Spencer and Yoshikazu Ishii and Jean-Denis Docquier and Gian Maria Rossolini and Laurent Poirel and Mariagrazia Perilli and Gianfranco Amicosante and Moreno Galleni and Alejandro Vila and Gabriel Gutkind and Timothy Palzkill and Alessandra Carattoli and Catherine Tooke and Philip Hinchliffe and Christopher Schofield and Bogdan I. Iorga and Thierry Naas and Yu Chen and Cesar Arias and Andrea Endimiani and Krisztina Papp-Wallace and Ryan Shields and Pranita Tamma and Robert Bonomo and Pablo Power},
journal = {Antimicrobial Agents and Chemotherapy},
year = {2026},
month = may,
doi = {10.1128/aac.01868-25},
url = {https://hal.science/hal-05787390v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Standardized numbering and alignment of the KPC family of β-lactamases
AU - Florencia Brunetti
AU - Steven Marshall
AU - Christopher Bethel
AU - Andrea Hujer
AU - Kristine Hujer
AU - Shozeb Haider
AU - Karen Bush
AU - Patricia Bradford
AU - Barry Kreiswirth
AU - James Spencer
AU - Yoshikazu Ishii
AU - Jean-Denis Docquier
AU - Gian Maria Rossolini
AU - Laurent Poirel
AU - Mariagrazia Perilli
AU - Gianfranco Amicosante
AU - Moreno Galleni
AU - Alejandro Vila
AU - Gabriel Gutkind
AU - Timothy Palzkill
AU - Alessandra Carattoli
AU - Catherine Tooke
AU - Philip Hinchliffe
AU - Christopher Schofield
AU - Bogdan I. Iorga
AU - Thierry Naas
AU - Yu Chen
AU - Cesar Arias
AU - Andrea Endimiani
AU - Krisztina Papp-Wallace
AU - Ryan Shields
AU - Pranita Tamma
AU - Robert Bonomo
AU - Pablo Power
PY - 2026
DA - 2026/05/29
JO - Antimicrobial Agents and Chemotherapy
DO - 10.1128/aac.01868-25
UR - https://hal.science/hal-05787390v1
AB - The KPC family of serine β-lactamases comprises more than 260 members. Some variants are associated with ceftazidime-avibactam resistance in clinical isolates, often linked to substitutions and/or insertions/deletions (i.e., INDELs) in three distinct loops of the KPC sequence: (i) the 164–179 loop (i.e., the Ω loop); (ii) the 237–243 loop; and (iii) the 267–275 loop. Inconsistencies in residue numbering across published reports, however, complicate the accurate annotation of KPC variants. We retrieved 267 KPC variant sequences from the Beta-Lactamase Database (BLDB) in September 2025 and analyzed sequence differences between variants using combined nucleotide and structure-guided alignment algorithms, supported by AlphaFold3 modeling in ambiguous cases. Variants were classified into four groups to comprehensively review sequence changes across the KPC family: substitutions only ( n = 126), deletions only ( n = 17), insertions only ( n = 66), and variants with two or more types of amino acid changes ( n = 57). Comparisons with previous reports indicate that many annotation errors stem from overlooking the absent residues 58 and 253 in the KPC consensus sequence, and that most inconsistencies in annotation and residue assignment occur in INDEL variants. To address these issues, we propose a standardized annotation scheme for substitutions, deletions, and insertions for the KPC family, based on the Ambler numbering system, and supported by structural information. This systematic scheme will help to standardize the description of newly emerging KPC variants and prevent discrepancies in future reports in the context of antimicrobial resistance.
SN - 0066-4804
SN - 1098-6596
ER -