• Gigante, V. et al. Multi-year analysis of the global preclinical antibacterial pipeline: trends and gaps. Antimicrob. Agents Chemother. 68, e0053524 (2024).


    Google Scholar
     

  • GBD 2021 Antimicrobial Resistance Collaborators Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. Lancet 404, 1199–1226 (2024).


    Google Scholar
     

  • Murray, C. J. et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399, 629–655 (2022).


    Google Scholar
     

  • Sati, H. et al. The WHO Bacterial Priority Pathogens List 2024: a prioritisation study to guide research, development, and public health strategies against antimicrobial resistance. Lancet Infect. Dis. 25, 1033–1043 (2025).


    Google Scholar
     

  • Müller, C. et al. A global view on carbapenem-resistant Acinetobacter baumannii. mBio 14, e02260-23 (2023).

  • Wenzler, E., Goff, D. A., Humphries, R. & Goldstein, E. J. C. Anticipating the unpredictable: a review of antimicrobial stewardship and acinetobacter infections. Infect. Dis. Ther. 6, 149–172 (2017).


    Google Scholar
     

  • Bostanghadiri, N. et al. Prevalence of colistin resistance in clinical isolates of Acinetobacter baumannii: a systematic review and meta-analysis. Antimicrob. Resist. Infect. Control 13, 24 (2024).


    Google Scholar
     

  • Mohamed, Y. F., Abou-Shleib, H. M., Khalil, A. M., El-Guink, N. M. & El-Nakeeb, M. A. Membrane permeabilization of colistin toward pan-drug resistant Gram-negative isolates. Braz. J. Microbiol. 47, 381–388 (2016).


    Google Scholar
     

  • Sabnis, A. et al. Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane. eLife 10, 1–26 (2021).


    Google Scholar
     

  • Aghapour, Z. et al. Molecular mechanisms related to colistin resistance in Enterobacteriaceae. Infect. Drug Resist. 12, 965–975 (2019).


    Google Scholar
     

  • Moffatt, J. H. et al. Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob. Agents Chemother. 54, 4971–4977 (2010).


    Google Scholar
     

  • Moffatt, J. H. et al. Insertion sequence ISAba11 is involved in colistin resistance and loss of lipopolysaccharide in Acinetobacter baumannii. Antimicrob. Agents Chemother. 55, 3022–3024 (2011).


    Google Scholar
     

  • Dahdouh, E. et al. A novel mutation in pmrB mediates colistin resistance during therapy of Acinetobacter baumannii. Int J. Antimicrob. Agents 49, 727–733 (2017).


    Google Scholar
     

  • Seleim, S. M., Mostafa, M. S., Ouda, N. H. & Shash, R. Y. The role of pmrCAB genes in colistin-resistant Acinetobacter baumannii. Sci. Rep. 12, 20951 (2022).


    Google Scholar
     

  • Lin, M.-F., Lin, Y.-Y. & Lan, C.-Y. Contribution of EmrAB efflux pumps to colistin resistance in Acinetobacter baumannii. J. Microbiol. 55, 130–136 (2017).


    Google Scholar
     

  • Tyers, M. & Wright, G. D. Drug combinations: a strategy to extend the life of antibiotics in the 21st century. Nat. Rev. Microbiol. 17, 141–155 (2019).


    Google Scholar
     

  • Shields, R. K. et al. High mortality rates among solid organ transplant recipients infected with extensively drug-resistant Acinetobacter baumannii: using in vitro antibiotic combination testing to identify the combination of a carbapenem and colistin as an effective treatment regimen. Diagn. Microbiol Infect. Dis. 70, 246–252 (2011).


    Google Scholar
     

  • Wareham, D. W. & Bean, D. C. In-vitro activity of polymyxin B in combination with imipenem, rifampicin and azithromycin versus multidrug resistant strains of Acinetobacter baumannii producing OXA-23 carbapenemases. Ann. Clin. Microbiol. Antimicrob. 5, 10 (2006).


    Google Scholar
     

  • Pankuch, G. A., Lin, G., Seifert, H. & Appelbaum, P. C. Activity of meropenem with and without ciprofloxacin and colistin against Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrob. Agents Chemother. 52, 333–336 (2008).


    Google Scholar
     

  • Guelfi, K. C. et al. In vitro evaluation of the antimicrobial activity of meropenem in combination with polymyxin B and gatifloxacin against Pseudomonas aeruginosa and Acinetobacter baumannii. J. Chemother. 20, 180–185 (2008).


    Google Scholar
     

  • Wang, X. et al. Colistin-phage combinations decrease antibiotic resistance in Acinetobacter baumannii via changes in envelope architecture. Emerg. Microbes Infect. 10, 2205–2219 (2021).


    Google Scholar
     

  • Sugrue, I., Ross, R. P. & Hill, C. Bacteriocin diversity, function, discovery and application as antimicrobials. Nat. Rev. Microbiol. 22, 556–571 (2024).


    Google Scholar
     

  • Soltani, S. et al. Bacteriocins as a new generation of antimicrobials: toxicity aspects and regulations. FEMS Microbiol. Rev. 45, fuaa039 (2021).


    Google Scholar
     

  • Telhig, S., Ben Said, L., Zirah, S., Fliss, I. & Rebuffat, S. Bacteriocins to Thwart Sbacterial resistance in gram negative bacteria. Front. Microbiol. 11, 586433 (2020).


    Google Scholar
     

  • Cotter, P. D., Ross, R. P. & Hill, C. Bacteriocins – A viable alternative to antibiotics? Nat. Rev. Microbiol 11, 95–105 (2013).


    Google Scholar
     

  • Naghmouchi, K. et al. Synergistic effect between colistin and bacteriocins in controlling Gram-negative pathogens and their potential to reduce antibiotic toxicity in mammalian epithelial cells. Antimicrob. Agents Chemother. 57, 2719–2725 (2013).


    Google Scholar
     

  • Chi, H. & Holo, H. Synergistic antimicrobial activity between the broad spectrum bacteriocin garvicin KS and nisin, farnesol and polymyxin B against gram-positive and gram-negative bacteria. Curr. Microbiol. 75, 272–277 (2018).


    Google Scholar
     

  • Thomas, V. M., Brown, R. M., Ashcraft, D. S. & Pankey, G. A. Synergistic effect between nisin and polymyxin B against pandrug-resistant and extensively drug-resistant Acinetobacter baumannii. Int. J. Antimicrob. Agents 53, 663–668 (2019).


    Google Scholar
     

  • Jahangiri, A. et al. Synergistic effect of two antimicrobial peptides, Nisin and P10 with conventional antibiotics against extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates. Micro. Pathog. 150, 104700 (2021).


    Google Scholar
     

  • Brunati, C. et al. Expanding the potential of NAI-107 for treating serious ESKAPE pathogens: synergistic combinations against Gram-negatives and bactericidal activity against non-dividing cells. J. Antimicrob. Chemother. 73, 414–424 (2018).


    Google Scholar
     

  • Mortzfeld, B. M., Bhattarai, S. K. & Bucci, V. Novel class IIb microcins show activity against Gram-negative ESKAPE and plant pathogens. Elife 13, RP102912 (2024).


    Google Scholar
     

  • Valcek, A. et al. Phenotypic Characterization and Heterogeneity among Modern Clinical Isolates of Acinetobacter baumannii. Microbiol. Spectr. 11, e0306122 (2023).


    Google Scholar
     

  • Jacobs, A. C. et al. AB5075, a highly virulent isolate of acinetobacter baumannii, as a model strain for the evaluation of pathogenesis and antimicrobial treatments. mBio 5, 10–1128 (2014).

  • Ayoub Moubareck, C. & Hammoudi Halat, D. Insights into acinetobacter baumannii: a review of microbiological, virulence, and resistance traits in a threatening nosocomial pathogen. Antibiotics 9, 119 (2020).


    Google Scholar
     

  • Iwatani, S., Zendo, T., Yoneyama, F., Nakayama, J. & Sonomoto, K. Characterization and structure analysis of a novel bacteriocin, lacticin Z, produced by Lactococcus lactis QU 14. Biosci. Biotechnol. Biochem. 71, 1984–1992 (2007).


    Google Scholar
     

  • Cintas, L. M. et al. Enterocins L50A and L50B, two novel bacteriocins from Enterococcus faecium L50, are related to staphylococcal hemolysins. J. Bacteriol. 180, 1988–1994 (1998).


    Google Scholar
     

  • Yoneyama, F. et al. Lacticin Q-mediated selective toxicity depending on physicochemical features of membrane components. Antimicrob. Agents Chemother. 55, 2446–2450 (2011).


    Google Scholar
     

  • Hofkens, N. et al. Microbisporicin (NAI-107) protects Galleria mellonella from infection with Neisseria gonorrhoeae. Microbiol. Spectr. 11, e0282523 (2023).


    Google Scholar
     

  • Hofkens, N. et al. Protective effect of microbisporicin (NAI-107) against vancomycin resistant Enterococcus faecium infection in a Galleria mellonella model. Sci. Rep. 14, 4786 (2024).


    Google Scholar
     

  • Fujita, K. et al. Structural analysis and characterization of lacticin Q, a novel bacteriocin belonging to a new family of unmodified bacteriocins of gram-positive bacteria. Appl. Environ. Microbiol. 73, 2871–2877 (2007).


    Google Scholar
     

  • Liu, X. et al. Identification of an N-terminal formylated, two-peptide bacteriocin from Enterococcus faecalis 710C. J. Agric. Food Chem. 59, 5602–5608 (2011).


    Google Scholar
     

  • Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493–500 (2024).


    Google Scholar
     

  • Acedo, J. Z. et al. Nuclear magnetic resonance solution structures of lacticin Q and aureocin A53 reveal a structural motif conserved among leaderless bacteriocins with broad-spectrum activity. Biochemistry 55, 733–742 (2016).


    Google Scholar
     

  • Yoneyama, F. et al. Lacticin Q, a lactococcal bacteriocin, causes high-level membrane permeability in the absence of specific receptors. Appl. Environ. Microbiol 75, 538–541 (2009).


    Google Scholar
     

  • Yoneyama, F. et al. Peptide-lipid huge toroidal pore, a new antimicrobial mechanism mediated by a lactococcal bacteriocin, lacticin Q. Antimicrob. Agents Chemother. 53, 3211–3217 (2009).


    Google Scholar
     

  • Netz, D. J. A., Bastos, M., do, C., de, F. & Sahl, H.-G. Mode of action of the antimicrobial peptide aureocin A53 from Staphylococcus aureus. Appl. Environ. Microbiol. 68, 5274–5280 (2002).


    Google Scholar
     

  • Lopalco, P., Stahl, J., Annese, C., Averhoff, B. & Corcelli, A. Identification of unique cardiolipin and monolysocardiolipin species in Acinetobacter baumannii. Sci. Rep. 7, 2972 (2017).


    Google Scholar
     

  • Ushiyama, F. et al. Lead optimization of 2-hydroxymethyl imidazoles as non-hydroxamate LpxC inhibitors: discovery of TP0586532. Bioorg. Med. Chem. 30, 115964 (2021).


    Google Scholar
     

  • Yoshida, I., Takata, I., Fujita, K., Takashima, H. & Sugiyama, H. TP0586532, a novel non-hydroxamate LpxC inhibitor: potentiating effect on in vitro activity of meropenem against carbapenem-resistant Enterobacteriaceae. Microbiol. Spectr. 10, e0082822 (2022).


    Google Scholar
     

  • Simpson, B. W. et al. Acinetobacter baumannii can survive with an outer membrane lacking lipooligosaccharide due to structural support from elongasome peptidoglycan synthesis. mBio 12, e0309921 (2021).


    Google Scholar
     

  • Carretero-Ledesma, M. et al. Phenotypic changes associated with Colistin resistance due to Lipopolysaccharide loss in Acinetobacter baumannii. Virulence 9, 930–942 (2018).


    Google Scholar
     

  • Kamoshida, G. et al. Lipopolysaccharide-deficient Acinetobacter baumannii due to colistin resistance is killed by neutrophil-produced lysozyme. Front. Microbiol. 11, 573 (2020).


    Google Scholar
     

  • Powers, M. J. & Trent, M. S. Phospholipid retention in the absence of asymmetry strengthens the outer membrane permeability barrier to last-resort antibiotics. Proc. Natl. Acad. Sci. USA 115, E8518–E8527 (2018).


    Google Scholar
     

  • Beceiro, A. et al. Biological cost of different mechanisms of colistin resistance and their impact on virulence in Acinetobacter baumannii. Antimicrob. Agents Chemother. 58, 518–526 (2014).


    Google Scholar
     

  • Boll, J. M. et al. A penicillin-binding protein inhibits selection of colistin-resistant, lipooligosaccharide-deficient Acinetobacter baumannii. Proc. Natl. Acad. Sci. USA 113, E6228–E6237 (2016).


    Google Scholar
     

  • Hernandez-Bird, J. et al. Resistance, heteroresistance, and fitness costs drive colistin treatment failure during Acinetobacter baumannii pneumonia. Proc. Natl. Acad. Sci. USA 123, e2515303123 (2026).


    Google Scholar
     

  • Charretier, Y. et al. Colistin heteroresistance and involvement of the PmrAB regulatory system in Acinetobacter baumannii. Antimicrob. Agents Chemother. 62, e00788–18 (2018).


    Google Scholar
     

  • Yau, W. et al. Colistin hetero-resistance in multidrug-resistant Acinetobacter baumannii clinical isolates from the Western Pacific region in the SENTRY antimicrobial surveillance programme. J. Infect. 58, 138–144 (2009).


    Google Scholar
     

  • Andersson, D. I., Nicoloff, H. & Hjort, K. Mechanisms and clinical relevance of bacterial heteroresistance. Nat. Rev. Microbiol 17, 479–496 (2019).


    Google Scholar
     

  • Novović, K. & Jovčić, B. Colistin resistance in Acinetobacter baumannii: molecular mechanisms and epidemiology. Antibiotics 12, 516 (2023).


    Google Scholar
     

  • Veeraraghavan, B. et al. A microbiological and structural analysis of the interplay between sulbactam/durlobactam and imipenem against penicillin-binding proteins (PBPs) of Acinetobacter spp. Antimicrob. Agents Chemother. 69, e0162724 (2025).


    Google Scholar
     

  • Hashizume, T., Ishino, F., Nakagawa, J., Tamaki, S. & Matsuhashi, M. Studies on the mechanism of action of imipenem (N-formimidoylthienamycin) in vitro: binding to the penicillin-binding proteins (PBPs) in Escherichia coli and Pseudomonas aeruginosa, and inhibition of enzyme activities due to the PBPs in E. coli. J. Antibiot. 37, 394–400 (1984).


    Google Scholar
     

  • Atanaskovic, I. & Kleanthous, C. Tools and approaches for dissecting protein bacteriocin import in gram-negative bacteria. Front. Microbiol. 10, 646 (2019).


    Google Scholar
     

  • Tenaillon, O., Denamur, E. & Matic, I. Evolutionary significance of stress-induced mutagenesis in bacteria. Trends Microbiol. 12, 264–270 (2004).


    Google Scholar
     

  • Pribis, J. P., Zhai, Y., Hastings, P. J. & Rosenberg, S. M. Stress-induced mutagenesis, gambler cells, and stealth targeting antibiotic-induced evolution. mBio 13, e0107422 (2022).


    Google Scholar
     

  • Manuse, S. et al. Bacterial persisters are a stochastically formed subpopulation of low-energy cells. PLoS Biol. 19, e3001194 (2021).


    Google Scholar
     

  • Shan, Y. et al. ATP-dependent persister formation in Escherichia coli. mBio 8, e02267–16 (2017).


    Google Scholar
     

  • Edelmann, D. & Berghoff, B. A. A shift in perspective: a role for the type I toxin TisB as persistence-stabilizing factor. Front. Microbiol. 13, 871699 (2022).


    Google Scholar
     

  • MacNair, C. R. et al. Overcoming mcr-1 mediated colistin resistance with colistin in combination with other antibiotics. Nat. Commun. 9, 458 (2018).


    Google Scholar
     

  • Maharramov, E. et al. Exploring the principles behind antibiotics with limited resistance. Nat. Commun. 16, 1842 (2025).


    Google Scholar
     

  • Kaneti, G., Sarig, H., Marjieh, I., Fadia, Z. & Mor, A. Simultaneous breakdown of multiple antibiotic resistance mechanisms in S. aureus. FASEB J. 27, 4834–4843 (2013).


    Google Scholar
     

  • Stokes, J. M. et al. Pentamidine sensitizes Gram-negative pathogens to antibiotics and overcomes acquired colistin resistance. Nat. Microbiol 2, 17028 (2017).


    Google Scholar
     

  • Lázár, V. et al. Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides. Nat. Microbiol 3, 718–731 (2018).


    Google Scholar
     

  • Blattner, F. R. et al. The complete genome sequence of Escherichia coli K-12. Science 277, 1453–1462 (1997).


    Google Scholar
     

  • Gabant, P. & Borrero, J. PARAGEN 1.0: a standardized synthetic gene library for fast cell-free bacteriocin synthesis. Front Bioeng. Biotechnol. 7, 213 (2019).


    Google Scholar
     

  • Lin, Y. et al. Assembly of long error-prone reads using de Bruijn graphs. Proc. Natl. Acad. Sci. USA 113, E8396–E8405 (2016).


    Google Scholar
     

  • Simão, F. A., Waterhouse, R. M., Ioannidis, P., Kriventseva, E. V. & Zdobnov, E. M. BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs. Bioinformatics 31, 3210–3212 (2015).


    Google Scholar
     

  • Cuccuru, G. et al. Orione, a web-based framework for NGS analysis in microbiology. Bioinformatics 30, 1928–1929 (2014).


    Google Scholar
     

  • Feldgarden, M. et al. AMRFinderPlus and the Reference Gene Catalog facilitate examination of the genomic links among antimicrobial resistance, stress response, and virulence. Sci. Rep. 11, 12728 (2021).


    Google Scholar
     

  • Krawczyk, P. S., Lipinski, L. & Dziembowski, A. PlasFlow: predicting plasmid sequences in metagenomic data using genome signatures. Nucleic Acids Res 46, e35 (2018).


    Google Scholar
     

  • Perrin, A. & Rocha, E. P. C. PanACoTA: a modular tool for massive microbial comparative genomics. NAR Genom. Bioinform. 3, lqaa106 (2021).


    Google Scholar
     

  • Morrissey, I. & Patel, J. B. Modification of antimicrobial susceptibility testing methods. J. Antimicrob. Chemother. 80, 2887–2888 (2025).


    Google Scholar
     

  • Cannella, S. E. et al. Stability, structural and functional properties of a monomeric, calcium-loaded adenylate cyclase toxin, CyaA, from Bordetella pertussis. Sci. Rep. 7, 42065 (2017).


    Google Scholar
     

  • Voegele, A. et al. A high-affinity calmodulin-binding site in the CyaA toxin translocation domain is essential for invasion of eukaryotic cells. Adv. Sci. 8, 2003630 (2021).


    Google Scholar
     

  • Subrini, O. et al. Characterization of a membrane-active peptide from the Bordetella pertussis CyaA toxin. J. Biol. Chem. 288, 32585–32598 (2013).


    Google Scholar
     

  • Sadi, M. et al. B2LiVe, a label-free 1D-NMR method to quantify the binding of amphitropic peptides or proteins to membrane vesicles. Cell Rep. Methods 3, 100624 (2023).


    Google Scholar