Extension of penA diversity within the genus Neisseria: characterization of a penA/ftsI homolog in Neisseria bacilliformis associated with elevated ceftriaxone MICs
- 1Department of Clinical Sciences, Institute of Tropical Medicine Antwerp, Antwerp, Belgium
- 2Department of Infection Control and Prevention, Faculty of Nursing, Toho University, Tokyo, Japan
- 3Department of Medicine, University of Cape Town, Cape Town, South Africa
Abstract
Reduced susceptibility to extended-spectrum cephalosporins in Neisseria gonorrhoeae is primarily mediated by structural alterations in penicillin-binding protein 2 (PBP2), encoded by penA, frequently arising through interspecies recombination with commensal Neisseria. While mosaic penA diversity has been extensively characterized in coccoid Neisseria species, rod-shaped commensals such as Neisseria bacilliformis remain poorly explored. Here, we investigated the β-lactam target repertoire of N. bacilliformis using whole-genome sequencing, comparative genomics, mutation profiling, and structural modeling. Fifteen N. bacilliformis genomes were analyzed, including eight isolates with elevated ceftriaxone minimum inhibitory concentrations (MIC) (range 0.094–1 µg/mL; median 0.5 µg/mL). Interrogation of the PubMLST locus NEIS1753 did not identify matches under default parameters. However, de novo annotation revealed a syntenic high-molecular-mass transpeptidase annotated as ftsI, occupying the conserved rsmH-ftsL-ftsI-murE chromosomal context observed in N. gonorrhoeae. BLASTP analysis demonstrated ~59%–61% amino-acid identity to gonococcal PBP2. Structural modeling using AlphaFold and template-based approaches confirmed preservation of the canonical class B penicillin-binding protein fold, including conserved catalytic motifs. Across 24 positions previously associated with altered cephalosporin susceptibility in gonococci, multiple canonical substitutions were conserved in N. bacilliformis, alongside lineage-specific variants not reported in N. gonorrhoeae. Interestingly, polymorphism at positions A328 and A341 was observed in isolates with higher MICs (1 µg/mL). Definitive genotype-phenotype associations could not be established. Recombination analysis did not identify discrete parental donors but suggested a complex evolutionary history. These findings demonstrate that N. bacilliformis encodes a structurally conserved PBP2 homolog annotated as FtsI and expand the landscape of β-lactam target diversity within the genus Neisseria.
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BibTeX
@article{manoharanbasil2026extension,
title = {{Extension of penA diversity within the genus Neisseria: characterization of a penA/ftsI homolog in Neisseria bacilliformis associated with elevated ceftriaxone MICs}},
author = {Sheeba Santhini Manoharan-Basil and Tessa de Block and Izumo Kanesaka and Saïd Abdellati and Thibaut Vanbaelen and Chris Kenyon},
journal = {Antimicrobial Agents and Chemotherapy},
year = {2026},
month = jul,
doi = {10.1128/aac.00392-26},
url = {https://doi.org/10.1128/aac.00392-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Extension of penA diversity within the genus Neisseria: characterization of a penA/ftsI homolog in Neisseria bacilliformis associated with elevated ceftriaxone MICs
AU - Sheeba Santhini Manoharan-Basil
AU - Tessa de Block
AU - Izumo Kanesaka
AU - Saïd Abdellati
AU - Thibaut Vanbaelen
AU - Chris Kenyon
PY - 2026
DA - 2026/07/23
JO - Antimicrobial Agents and Chemotherapy
DO - 10.1128/aac.00392-26
UR - https://doi.org/10.1128/aac.00392-26
AB - Reduced susceptibility to extended-spectrum cephalosporins in Neisseria gonorrhoeae is primarily mediated by structural alterations in penicillin-binding protein 2 (PBP2), encoded by penA, frequently arising through interspecies recombination with commensal Neisseria. While mosaic penA diversity has been extensively characterized in coccoid Neisseria species, rod-shaped commensals such as Neisseria bacilliformis remain poorly explored. Here, we investigated the β-lactam target repertoire of N. bacilliformis using whole-genome sequencing, comparative genomics, mutation profiling, and structural modeling. Fifteen N. bacilliformis genomes were analyzed, including eight isolates with elevated ceftriaxone minimum inhibitory concentrations (MIC) (range 0.094–1 µg/mL; median 0.5 µg/mL). Interrogation of the PubMLST locus NEIS1753 did not identify matches under default parameters. However, de novo annotation revealed a syntenic high-molecular-mass transpeptidase annotated as ftsI, occupying the conserved rsmH-ftsL-ftsI-murE chromosomal context observed in N. gonorrhoeae. BLASTP analysis demonstrated ~59%–61% amino-acid identity to gonococcal PBP2. Structural modeling using AlphaFold and template-based approaches confirmed preservation of the canonical class B penicillin-binding protein fold, including conserved catalytic motifs. Across 24 positions previously associated with altered cephalosporin susceptibility in gonococci, multiple canonical substitutions were conserved in N. bacilliformis, alongside lineage-specific variants not reported in N. gonorrhoeae. Interestingly, polymorphism at positions A328 and A341 was observed in isolates with higher MICs (1 µg/mL). Definitive genotype-phenotype associations could not be established. Recombination analysis did not identify discrete parental donors but suggested a complex evolutionary history. These findings demonstrate that N. bacilliformis encodes a structurally conserved PBP2 homolog annotated as FtsI and expand the landscape of β-lactam target diversity within the genus Neisseria.
SN - 0066-4804
SN - 1098-6596
ER -