Shared Resistance, Phage-Receptor, and Biofilm Determinants in Antibiotic-Resistant Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii: A Bibliometric and Gene-Network Analysis of Phage Cocktail Research.
- 1School of Public Health, Hebei Medical University, Shijiazhuang 050017, China.
- 2Hebei Key Laboratory of Pathogens and Epidemiology of Infectious Diseases, Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang 050021, China.
Abstract
Background/objectives
Antimicrobial resistance has renewed interest in bacteriophage cocktails as antibacterial and adjunctive agents, but the global research landscape and the bacterial determinants that constrain cocktail performance have not been mapped within a single framework. We quantified global phage-cocktail research and tested whether antibiotic-resistance, phage-receptor, and biofilm gene sets converge on shared genes in three Gram-negative pathogens representing three bacterial orders.Methods
The Web of Science Core Collection was searched on 5 July 2026 (query "phage" and "cocktail"). After deduplication and screening, 1598 articles and reviews (1992-2026) were analyzed with bibliometric workflows, citation-burst and co-citation analyses, and a focused China-United States comparison. Because these are the two leading producers and represent the dominant biocontrol and clinical research models, the comparison is deliberately restricted to them and is not presented as a global ranking. Resistance (R), phage receptor/defense (P), and biofilm (B) gene sets were curated for Pseudomonas aeruginosa PAO1, Escherichia coli K-12, and Acinetobacter baumannii ATCC 17978; overlaps were tested by one-sided hypergeometric tests with Benjamini-Hochberg correction and against size-matched control gene sets, followed by STRING protein-protein interaction and KEGG/GO enrichment. Orthologous conservation was assessed with KEGG Orthology in addition to gene-symbol matching.Results
Annual output grew from 2 records (1992-1996) to 873 (2022-2026; 54.6% of the corpus), led by the USA (322 records) and China (292). Phage-receptor-biofilm overlaps were strongly enriched in all three species (29, 7, and 28 genes; odds ratios 47.0, 8.1, and 31.7; all P ≤ 7.6 × 10⁻⁵), whereas resistance-phage-receptor overlaps were strongly enriched in PAO1 (18 genes; odds ratio 17.7) and K-12 (26 genes; odds ratio 30.2) but not in A. baumannii (9 genes; odds ratio 1.8; P = 0.088). Four unrelated control gene sets showed no enrichment in any species (odds ratios 0-1.9; P ≥ 0.42). Candidate networks formed alginate, Psl-Pel, lipopolysaccharide-modification, and SOS/porin modules; KEGG enrichment converged on biofilm formation and cationic antimicrobial peptide resistance; 14 of the 18 symbol-level conserved genes were corroborated by shared KEGG Orthology assignments.Conclusions
Phage-cocktail research has entered a phase of rapid growth, with hotspots converging on combination therapy and formulation. Biofilm-matrix synthesis and surface-appendage assembly form a transferable interface between phage adsorption and biofilm formation across three bacterial orders, whereas the coupling between antibiotic resistance and phage-receptor genes is lineage-restricted. Because the R, P, and B sets overlap by construction, these convergences are hypothesis-generating and require experimental validation before they can be used as design rules.
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BibTeX
@article{zhang2026shared,
title = {{Shared Resistance, Phage-Receptor, and Biofilm Determinants in Antibiotic-Resistant Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii: A Bibliometric and Gene-Network Analysis of Phage Cocktail Research.}},
author = {Wei Zhang and Peilin Zheng and Baohua He and Qi Li},
journal = {Antibiotics (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/antibiotics15100950},
url = {https://europepmc.org/article/MED/42938691},
note = {CC BY},
}
RIS
TY - JOUR
TI - Shared Resistance, Phage-Receptor, and Biofilm Determinants in Antibiotic-Resistant Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii: A Bibliometric and Gene-Network Analysis of Phage Cocktail Research.
AU - Wei Zhang
AU - Peilin Zheng
AU - Baohua He
AU - Qi Li
PY - 2026
DA - 2026/09/24
JO - Antibiotics (Basel, Switzerland)
DO - 10.3390/antibiotics15100950
UR - https://europepmc.org/article/MED/42938691
AB - Background/objectives Antimicrobial resistance has renewed interest in bacteriophage cocktails as antibacterial and adjunctive agents, but the global research landscape and the bacterial determinants that constrain cocktail performance have not been mapped within a single framework. We quantified global phage-cocktail research and tested whether antibiotic-resistance, phage-receptor, and biofilm gene sets converge on shared genes in three Gram-negative pathogens representing three bacterial orders.Methods The Web of Science Core Collection was searched on 5 July 2026 (query "phage" and "cocktail"). After deduplication and screening, 1598 articles and reviews (1992-2026) were analyzed with bibliometric workflows, citation-burst and co-citation analyses, and a focused China-United States comparison. Because these are the two leading producers and represent the dominant biocontrol and clinical research models, the comparison is deliberately restricted to them and is not presented as a global ranking. Resistance (R), phage receptor/defense (P), and biofilm (B) gene sets were curated for Pseudomonas aeruginosa PAO1, Escherichia coli K-12, and Acinetobacter baumannii ATCC 17978; overlaps were tested by one-sided hypergeometric tests with Benjamini-Hochberg correction and against size-matched control gene sets, followed by STRING protein-protein interaction and KEGG/GO enrichment. Orthologous conservation was assessed with KEGG Orthology in addition to gene-symbol matching.Results Annual output grew from 2 records (1992-1996) to 873 (2022-2026; 54.6% of the corpus), led by the USA (322 records) and China (292). Phage-receptor-biofilm overlaps were strongly enriched in all three species (29, 7, and 28 genes; odds ratios 47.0, 8.1, and 31.7; all P ≤ 7.6 × 10⁻⁵), whereas resistance-phage-receptor overlaps were strongly enriched in PAO1 (18 genes; odds ratio 17.7) and K-12 (26 genes; odds ratio 30.2) but not in A. baumannii (9 genes; odds ratio 1.8; P = 0.088). Four unrelated control gene sets showed no enrichment in any species (odds ratios 0-1.9; P ≥ 0.42). Candidate networks formed alginate, Psl-Pel, lipopolysaccharide-modification, and SOS/porin modules; KEGG enrichment converged on biofilm formation and cationic antimicrobial peptide resistance; 14 of the 18 symbol-level conserved genes were corroborated by shared KEGG Orthology assignments.Conclusions Phage-cocktail research has entered a phase of rapid growth, with hotspots converging on combination therapy and formulation. Biofilm-matrix synthesis and surface-appendage assembly form a transferable interface between phage adsorption and biofilm formation across three bacterial orders, whereas the coupling between antibiotic resistance and phage-receptor genes is lineage-restricted. Because the R, P, and B sets overlap by construction, these convergences are hypothesis-generating and require experimental validation before they can be used as design rules.
SN - 2079-6382
ER -