Novel bifunctional antibacterial peptides mediated by a covalent conjugation strategy combat priority multidrug-resistant gram-negative pathogens through dual targets

Murray CJL, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, et al. Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. Lancet. 2022;399:629–55.

Article  CAS  Google Scholar 

WHO bacterial priority pathogens list, 2024: Bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. 2024. https://www.who.int/publications/i/item/9789240093461.

El-Sayed Ahmed M, Zhong LL, Shen C, Yang Y, Doi Y, Tian GB. Colistin and Its Role in the Era of Antibiotic Resistance: An Extended Review (2000–2019). Emerg Microbes Infect. 2020;9:868–85.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee JY, Na IY, Park YK, Ko KS. Genomic Variations between Colistin-Susceptible and -Resistant Pseudomonas Aeruginosa Clinical Isolates and Their Effects on Colistin Resistance. J Antimicrob Chemother. 2014;69:1248–56.

Article  CAS  PubMed  Google Scholar 

Miller AK, Brannon MK, Stevens L, Johansen HK, Selgrade SE, Miller SI, et al. PhoQ Mutations Promote Lipid A Modification and Polymyxin Resistance of Pseudomonas Aeruginosa Found in Colistin-Treated Cystic Fibrosis Patients. Antimicrob Agents Chemother. 2011;55:5761–69.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mlynarcik P, Kolar M. Molecular Mechanisms of Polymyxin Resistance and Detection of Mcr Genes. Biomed Pap. 2019;163:28–38.

Article  Google Scholar 

Trebosc V, Gartenmann S, Tötzl M, Lucchini V, Schellhorn B, Pieren M, et al. Dissecting Colistin Resistance Mechanisms in Extensively Drug-Resistant Acinetobacter Baumannii Clinical Isolates. mBio. 2019;10:e01083–19.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lima WG, Alves MC, Cruz WS, Paiva MC. Chromosomally Encoded and Plasmid-mediated Polymyxins Resistance in Acinetobacter Baumannii: A Huge Public Health Threat. Eur J Clin Microbiol Infect Dis. 2018;37:1009–19.

Article  CAS  PubMed  Google Scholar 

Perez F, El Chakhtoura NG, Yasmin M, Bonomo RA. Polymyxins: To Combine or Not to Combine?. Antibiotics. 2019;8:38.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Poirel L, Jayol A, Nordmann P. Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes. Clin Microbiol Rev. 2017;30:557–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sherry N, Howden B. Emerging Gram-negative Resistance to Last-Line Antimicrobial Agents Fosfomycin, Colistin and Ceftazidime-Avibactam – Epidemiology, Laboratory Detection and Treatment Implications. Expert Rev Anti Infect Ther. 2018;16:289–306.

Article  CAS  PubMed  Google Scholar 

Jeannot K, Bolard A, Plésiat P. Resistance to Polymyxins in Gram-Negative Organisms. Int J Antimicrob Agents. 2017;49:526–35.

Article  CAS  PubMed  Google Scholar 

Roberts KD. A Synthetic Lipopeptide Targeting Top-Priority Multidrug-Resistant Gram-Negative Pathogens. Nat Commun. 2022;13:1625.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang Y, Zhao C, Wang Q, Wang X, Chen H, Li H, et al. Evaluation of the in Vitro Activity of New Polymyxin B Analogue SPR206 against Clinical MDR, Colistin-Resistant and Tigecycline-Resistant Gram-Negative Bacilli. J Antimicrob Chemother. 2020;75:2609–15.

Article  CAS  PubMed  Google Scholar 

Cui AL, Yang HX, Yi H, Lv M, Peng XJ, Zheng GH, et al. Design, Synthesis, and Bioactivity Investigation of Novel Cyclic Lipopeptide Antibiotics Targeting Top-Priority Multidrug-Resistant Gram-Negative Bacteria. Eur J Med Chem. 2024;280:116924.

Article  CAS  PubMed  Google Scholar 

Brown P, Abbott E, Abdulle O, Boakes S, Coleman S, Divall N, et al. Design of Next Generation Polymyxins with Lower Toxicity: The Discovery of SPR206. ACS Infect Dis. 2019;5:1645–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sherman DJ, Xie R, Taylor RJ, George AH, Okuda S, Foster PJ, et al. Lipopolysaccharide is transported to the cell surface by a membrane-to-membrane protein bridge. Science. 2018;359:798–801.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Okuda S, Sherman DJ, Silhavy TJ, Ruiz N, Kahne D. Lipopolysaccharide Transport and Assembly at the Outer Membrane: The PEZ Model. Nat Rev Microbiol. 2016;14:337–45.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vetterli SU, Moehle K, Robinson JA. Synthesis and Antimicrobial Activity against Pseudomonas Aeruginosa of Macrocyclic β-Hairpin Peptidomimetic Antibiotics Containing N-Methylated Amino Acids. Bioorg Med Chem. 2016;24:6332–9.

Article  CAS  PubMed  Google Scholar 

Martin-Loeches I, Dale GE, Torres A. Murepavadin: A New Antibiotic Class in the Pipeline. Expert Rev Anti Infect Ther. 2018;16:259–68.

Article  CAS  PubMed  Google Scholar 

Schuster M, Brabet E, Oi KK, Desjonquères N, Moehle K, Le Poupon K, et al. Peptidomimetic Antibiotics Disrupt the Lipopolysaccharide Transport Bridge of Drug-Resistant Enterobacteriaceae. Sci Adv. 2023;9:eadg3683.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pahil KS, Gilman M, Baidin V, Clairfeuille T, Mattei P, Bieniossek C, et al. A New Antibiotic Traps Lipopolysaccharide in Its Intermembrane Transporter. Nature. 2024;625:572–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Miller RD, Iinishi A, Modaresi SM, Yoo BK, Curtis TD, Lariviere PJ, et al. Computational Identification of a Systemic Antibiotic for Gram-Negative Bacteria. Nat Microbiol. 2022;7:1661–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Imai Y, Meyer KJ, Iinishi A, Favre-Godal Q, Green R, Manuse S, et al. A New Antibiotic Selectively Kills Gram-Negative Pathogens. Nature. 2019;576:459–64.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clairfeuille T, Buchholz KR, Li Q, Verschueren E, Liu P, Sangaraju D, et al. Structure of the Essential Inner Membrane Lipopolysaccharide-PbgA Complex. Nature. 2020;584:479–83.

Article  CAS  PubMed  Google Scholar 

Yamauchi R, Kawano K, Yamaoka Y, Taniguchi A, Yano Y, Takasu K, et al. Development of Antimicrobial Peptide-Antibiotic Conjugates to Improve the Outer Membrane Permeability of Antibiotics Against Gram-Negative Bacteria. ACS Infect Dis. 2022;8:2339–47.

Article  CAS  PubMed  Google Scholar 

Li Y, Dong Y, Lu J, Zhang J, Feng M, Feng J. Design, synthesis and antibacterial activity of novel colistin derivatives with thioether bond-mediated cyclic scaffold. J Antibiot. 2023;76:260–9.

Article  CAS  Google Scholar 

Campbell RE, Chen CH, Edelstein CL. Overview of Antibiotic-Induced Nephrotoxicity. Kidney Int Rep. 2023;8:2211–25.

Article  PubMed  PubMed Central  Google Scholar 

Espinel-Ingroff A, Fothergill A, Ghannoum M, Manavathu E, Ostrosky-Zeichner L, Pfaller M, et al. Quality control and reference guidelines for CLSI broth microdilution susceptibility method (M 38-A document) for amphotericin B, itraconazole, posaconazole, and voriconazole. J Clin Microbiol. 2005;43:5243–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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