{"id":169394,"date":"2025-09-30T01:43:09","date_gmt":"2025-09-30T01:43:09","guid":{"rendered":"https:\/\/www.newsbeep.com\/uk\/169394\/"},"modified":"2025-09-30T01:43:09","modified_gmt":"2025-09-30T01:43:09","slug":"polymyxin-b-lethality-requires-energy-dependent-outer-membrane-disruption","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/uk\/169394\/","title":{"rendered":"Polymyxin B lethality requires energy-dependent outer membrane disruption"},"content":{"rendered":"

Fanous, J. et al. Limited impact of Salmonella stress and persisters on antibiotic clearance. Nature https:\/\/doi.org\/10.1038\/s41586-024-08506-6<\/a> (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lopatkin, A. J. et al. Metabolic state more accurately predicts antibiotic lethality than growth rate. Nat. Microbiol. 4, 2109\u20132117 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Conlon, B. P. et al. Persister formation in Staphylococcus aureus is associated with ATP depletion. Nat. Microbiol. 1, 16051 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Manuse, S. et al. Bacterial persisters are a stochastically formed subpopulation of low-energy cells. PLoS Biol. 19, e3001194 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ahmad, M., Aduru, S. V., Smith, R. P., Zhao, Z. & Lopatkin, A. J. The role of bacterial metabolism in antimicrobial resistance. Nat. Rev. Microbiol. https:\/\/doi.org\/10.1038\/s41579-025-01155-0<\/a> (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hurdle, J. G., O\u2019Neill, A. J., Chopra, I. & Lee, R. E. Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections. Nat. Rev. Microbiol. 9, 62\u201375 (2011).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Fisher, R. A., Gollan, B. & Helaine, S. Persistent bacterial infections and persister cells. Nat. Rev. Microbiol. 15, 453\u2013464 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Stokes, J. M., Lopatkin, A. J., Lobritz, M. A. & Collins, J. J. Bacterial metabolism and antibiotic efficacy. Cell Metab. 30, 251\u2013259 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, B. et al. Antibacterial diamines targeting bacterial membranes. J. Med. Chem. 59, 3140\u20133151 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Uppu, D.S.S.M. et al. Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria. PLoS One 12, e0183263 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kim, W. et al. A new class of synthetic retinoid antibiotics effective against bacterial persisters. Nature 556, 103\u2013107 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gray, D. A. et al. Membrane depolarization kills dormant Bacillus subtilis cells by generating a lethal dose of ROS. Nat. Commun. 15, 6877 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zheng, E. J. et al. Discovery of antibiotics that selectively kill metabolically dormant bacteria. Cell Chem. Biol. 31, 712\u2013728.e9 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ledger, E. V. K., Sabnis, A. & Edwards, A. M. Polymyxin and lipopeptide antibiotics: membrane-targeting drugs of last resort. Microbiology 168, 001136 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Nang, S. C., Azad, M. A. K., Velkov, T., Zhou, Q. T. & Li, J. Rescuing the last-line polymyxins: achievements and challenges. Pharm. Rev. 73, 679\u2013728 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kaye, K. S. et al. Efficacy and safety of sulbactam-durlobactam versus colistin for the treatment of patients with serious infections caused by Acinetobacter baumannii-calcoaceticus complex: a multicentre, randomised, active-controlled, phase 3, non-inferiority clinical trial (ATTACK). Lancet Infect. Dis. 23, 1072\u20131084 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Paul, M. et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect. Dis. 18, 391\u2013400 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Velkov, T., Thompson, P. E., Nation, R. L. & Li, J. Structure-activity relationships of polymyxin antibiotics. J. Med Chem. 53, 1898\u20131916 (2010).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pristovsek, P. & Kidric, J. Solution structure of polymyxins B and E and effect of binding to lipopolysaccharide: an NMR and molecular modeling study. J. Med Chem. 42, 4604\u20134613 (1999).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Buchholz, K. R. et al. Potent activity of polymyxin B is associated with long-lived super-stoichiometric accumulation mediated by weak-affinity binding to lipid A. Nat. Commun. 15, 4733 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Trimble, M. J., Mlyn\u00e1r\u010dik, P., Kol\u00e1\u0159, M. & Hancock, R. E. Polymyxin: alternative mechanisms of action and resistance. Cold Spring Harb. Perspect. Med. 6, a025288 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Manioglu, S. et al. Antibiotic polymyxin arranges lipopolysaccharide into crystalline structures to solidify the bacterial membrane. Nat. Commun. 13, 6195 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Benn, G., Silhavy, T. J., Kleanthous, C. & Hoogenboom, B. W. Antibiotics and hexagonal order in the bacterial outer membrane. Nat. Commun. 14, 4772 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Manioglu, S. et al. Reply to: Antibiotics and hexagonal order in the bacterial outer membrane. Nat. Commun. 14, 4773 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dixon, R. A. & Chopra, I. Polymyxin B and polymyxin B nonapeptide alter cytoplasmic membrane permeability in Escherichia coli. J. Antimicrob. Chemother. 18, 557\u2013563 (1986).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dixon, R. A. & Chopra, I. Leakage of periplasmic proteins from Escherichia coli mediated by polymyxin B nonapeptide. Antimicrob. Agents Chemother. 29, 781\u2013788 (1986).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sabnis, A. et al. Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane. Elife 10, e65836 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Humphrey, M. et al. Colistin resistance in Escherichia coli confers protection of the cytoplasmic but not outer membrane from the polymyxin antibiotic. Microbiology 167, 001104 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hancock, R. E. & Bell, A. Antibiotic uptake into gram-negative bacteria. Eur. J. Clin. Microbiol. Infect. Dis. 7, 713\u2013720 (1988).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hancock, R. E. & Chapple, D. S. Peptide antibiotics. Antimicrob. Agents Chemother. 43, 1317\u20131323 (1999).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chung, E. S., Wi, Y. M. & Ko, K. S. Variation in formation of persister cells against colistin in Acinetobacter baumannii isolates and its relationship with treatment failure. J. Antimicrob. Chemother. 72, 2133\u20132135 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Cui, P. et al. Disruption of membrane by colistin kills uropathogenic Escherichia coli persisters and enhances killing of other antibiotics. Antimicrob. Agents Chemother. 60, 6867\u20136871 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

McCall, I. C., Shah, N., Govindan, A., Baquero, F. & Levin, B. R. Antibiotic killing of diversely generated populations of nonreplicating bacteria. Antimicrob. Agents Chemother. 63, e02360\u201318 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zavascki, A. P. et al. Pharmacokinetics of intravenous polymyxin B in critically ill patients. Clin. Infect. Dis. 47, 1298\u20131304 (2008).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Hanafin, P. O. et al. A population pharmacokinetic model of polymyxin B based on prospective clinical data to inform dosing in hospitalized patients. Clin. Microbiol. Infect. 29, 1174\u20131181 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Pogue, J. M. et al. Polymyxin susceptibility testing and interpretive breakpoints: recommendations from the United States Committee on Antimicrobial Susceptibility Testing (USCAST). Antimicrob. Agents Chemother. 64, e01495\u201319 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Benn, G. et al. Phase separation in the outer membrane of Escherichia coli. Proc. Natl Acad. Sci. USA 118, e2112237118 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Benn, G. et al. OmpA controls order in the outer membrane and shares the mechanical load. Proc. Natl Acad. Sci. USA 121, e2416426121 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

MacNair, C. R. et al. Overcoming mcr-1 mediated colistin resistance with colistin in combination with other antibiotics. Nat. Commun. 9, 458 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Heesterbeek, D. A. et al. Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases. EMBO J. 38, e99852 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sabnis, A. & Edwards, A. M. Lipopolysaccharide as an antibiotic target. Biochim. Biophys. Acta Mol. Cell Res. 1870, 119507 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

May, J. M. et al. The antibiotic novobiocin binds and activates the ATPase that powers lipopolysaccharide transport. J. Am. Chem. Soc. 139, 17221\u201317224 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mandler, M. D. et al. Novobiocin enhances polymyxin activity by stimulating lipopolysaccharide transport. J. Am. Chem. Soc. 140, 6749\u20136753 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yokota, S. I. et al. Release of large amounts of lipopolysaccharides from Pseudomonas aeruginosa cells reduces their susceptibility to colistin. Int. J. Antimicrob. Agents 51, 888\u2013896 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Zhang, B. et al. Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage. Commun. Biol. 6, 409 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ling, Z. et al. Epidemiology of mobile colistin resistance genes mcr-1 to mcr-9. J. Antimicrob. Chemother. 75, 3087\u20133095 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Liu et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect. Dis. 16, 161\u2013168 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Schumann, A. et al. Site-selective modifications by lipid A phosphoethanolamine transferases linked to colistin resistance and bacterial fitness. mSphere 9, e0073124 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Yang, Q. et al. Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms. Nat. Commun. 8, 2054 (2017).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Weerakoon, D., Petrov, K., Pedebos, C. & Khalid, S. Polymyxin B1 within the E. coli cell envelope: insights from molecular dynamics simulations. Biophys. Rev. 13, 1061\u20131070 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Chung, E. S. & Ko, K. S. Eradication of persister cells of Acinetobacter baumannii through combination of colistin and amikacin antibiotics. J. Antimicrob. Chemother. 74, 1277\u20131283 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sahalan, A. Z. & Dixon, R. A. Role of the cell envelope in the antibacterial activities of polymyxin B and polymyxin B nonapeptide against Escherichia coli. Int J. Antimicrob. Agents 31, 224\u2013227 (2008).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Paracini, N., Clifton, L. A., Skoda, M. W. A. & Lakey, J. H. Liquid crystalline bacterial outer membranes are critical for antibiotic susceptibility. Proc. Natl Acad. Sci. USA 115, E7587\u2013E7594 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ginez, L. D. et al. Changes in fluidity of the E. coli outer membrane in response to temperature, divalent cations and polymyxin-B show two different mechanisms of membrane fluidity adaptation. FEBS J. 289, 3550\u20133567 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

McLeod, G. I. & Spector, M. P. Starvation- and stationary-phase-induced resistance to the antimicrobial peptide polymyxin B in Salmonella typhimurium is RpoS (sigma(S)) independent and occurs through both phoP-dependent and -independent pathways. J. Bacteriol. 178, 3683\u20133688 (1996).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Seo, J., Na, I. Y. & Ko, K. S. Antibiotic efficacy in Escherichia coli and Klebsiella pneumoniae under nutrient limitation and effectiveness of colistin-based antibiotic combinations to eradicate persister cells. Curr. Microbiol. 81, 34 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dwyer, D. J., Kohanski, M. A. & Collins, J. J. Role of reactive oxygen species in antibiotic action and resistance. Curr. Opin. Microbiol. 12, 482\u2013489 (2009).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ma, B. et al. The antimicrobial peptide thanatin disrupts the bacterial outer membrane and inactivates the NDM-1 metallo-\u03b2-lactamase. Nat. Commun. 10, 3517 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wei, X. et al. Murepavadin induces envelope stress response and enhances the killing efficacies of \u03b2-lactam antibiotics by impairing the outer membrane integrity of Pseudomonas aeruginosa. Microbiol. Spectr. 11, e0125723 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Werneburg, M. et al. Inhibition of lipopolysaccharide transport to the outer membrane in Pseudomonas aeruginosa by peptidomimetic antibiotics. Chembiochem 13, 1767\u20131775 (2012).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Goode, A., Yeh, V. & Bonev, B. B. Interactions of polymyxin B with lipopolysaccharide-containing membranes. Faraday Discuss. 232, 317\u2013329 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sampson, T. R. et al. Rapid killing of Acinetobacter baumannii by polymyxins is mediated by a hydroxyl radical death pathway. Antimicrob. Agents Chemother. 56, 5642\u20135649 (2012).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Gadar, K. et al. Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-negative bacteria. Commun. Biol. 6, 937 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Brochmann, R. P. et al. Bactericidal effect of colistin on planktonic Pseudomonas aeruginosa is independent of hydroxyl radical formation. Int. J. Antimicrob. Agents 43, 140\u2013147 (2014).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kolpen, M. et al. Increased bactericidal activity of colistin on Pseudomonas aeruginosa biofilms in anaerobic conditions. Pathog. Dis. 74, ftv086 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Koike, M., Iida, K. & Matsuo, T. Electron microscopic studies on mode of action of polymyxin. J. Bacteriol. 97, 448\u2013452 (1969).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lounatmaa, K., M\u00e4kel\u00e4, P. H. & Sarvas, M. Effect of polymyxin on the ultrastructure of the outer membrane of wild-type and polymyxin-resistant strain of Salmonella. J. Bacteriol. 127, 1400\u20131407 (1976).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Manning, A. J. & Kuehn, M. J. Contribution of bacterial outer membrane vesicles to innate bacterial defense. BMC Microbiol. 11, 258 (2011).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Park, J. et al. A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii. Elife 10, e66988 (2021).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Kulkarni, H. M., Nagaraj, R. & Jagannadham, M. V. Protective role of E. coli outer membrane vesicles against antibiotics. Microbiol. Res. 181, 1\u20137 (2015).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sabnis, A., Ledger, E. V. K., Pader, V. & Edwards, A. M. Antibiotic interceptors: creating safe spaces for bacteria. PLoS Pathog. 14, e1006924 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

McBroom, A. J. & Kuehn, M. J. Release of outer membrane vesicles by Gram-negative bacteria is a novel envelope stress response. Mol. Microbiol. 63, 545\u2013558 (2007).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Brand, C., Newton-Foot, M., Grobbelaar, M. & Whitelaw, A. Antibiotic-induced stress responses in Gram-negative bacteria and their role in antibiotic resistance. J. Antimicrob. Chemother. 80, 1165\u20131184 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Steenhuis, M., Ten Hagen-Jongman, C. M., van Ulsen, P. & Luirink, J. Stress-based high-throughput screening assays to identify inhibitors of cell envelope biogenesis. Antibiotics 9, 808 (2020).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Audrain, B. et al. Induction of the Cpx envelope stress pathway contributes to Escherichia coli tolerance to antimicrobial peptides. Appl. Environ. Microbiol. 79, 7770\u20137779 (2013).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Erickson, K.D. & Detweiler, C.S. The Rcs phosphorelay system is specific to enteric pathogens\/commensals and activates ydeI, a gene important for persistent Salmonella infection of mice. Mol. Microbiol. 62, 883\u2013894 (2006).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wang, D., Korban, S. S. & Zhao, Y. The Rcs phosphorelay system is essential for pathogenicity in Erwinia amylovora. Mol. Plant Pathol. 10, 277\u2013290 (2009).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Rojas, E. R. et al. The outer membrane is an essential load-bearing element in Gram-negative bacteria. Nature 559, 617\u2013621 (2018).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Arunmanee, W. et al. Gram-negative trimeric porins have specific LPS binding sites that are essential for porin biogenesis. Proc. Natl Acad. Sci. USA 113, E5034\u2013E5043 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Peterson, J. H., Yang, L., Gumbart, J. C. & Bernstein, H. D. Conserved lipid-facing basic residues promote the insertion of the porin OmpC into the E. coli outer membrane. mBio 16, e0331924 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Webby, M. N. et al. Lipids mediate supramolecular outer membrane protein assembly in bacteria. Sci. Adv. 8, eadc9566 (2022).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Davis, K. P. et al. Critical role of growth medium for detecting drug interactions in Gram-negative bacteria that model in vivo responses. mBio 15, e0015924 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Heithoff, D. M. et al. Re-evaluation of FDA-approved antibiotics with increased diagnostic accuracy for assessment of antimicrobial resistance. Cell Rep. Med. 4, 101023 (2023).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Duong, L. et al. Bactericidal activity of mammalian histones is caused by large membrane pore formation. Cell Rep. 44, 115658 (2025).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Fierer, J. & Finley, F. Lethal effect of complement and lysozyme on polymyxin-treated, serum-resistant Gram-negative bacilli. J. Infect. Dis. 140, 581\u2013589 (1979).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Leeson, M. C., Fujihara, Y. & Morrison, D. C. Evidence for lipopolysaccharide as the predominant proinflammatory mediator in supernatants of antibiotic-treated bacteria. Infect. Immun. 62, 4975\u20134980 (1994).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Jensen, K. F. The Escherichia coli K-12 \u201cwild types\u201d W3110 and MG1655 have an rph frameshift mutation that leads to pyrimidine starvation due to low pyrE expression levels. J. Bacteriol. 175, 3401\u20133407 (1993).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Silhavy T. J., Berman M. L. & Enquist L. W. Experiments with Gene Fusions (Cold Spring Harbor Laboratory Press, 1984).<\/p>\n

Braun, M. & Silhavy, T. J. Imp\/OstA is required for cell envelope biogenesis in Escherichia coli. Mol. Microbiol. 45, 1289\u20131302 (2002).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Sampson, B. A., Misra, R. & Benson, S. A. Identification and characterization of a new gene of Escherichia coli K-12 involved in outer membrane permeability. Genetics 122, 491\u2013501 (1989).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Mobley, H. L. et al. Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains. Infect. Immun. 58, 1281\u20131289 (1990).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Dortet, L., Br\u00e9chard, L., Poirel, L. & Nordmann, P. Rapid detection of carbapenemase-producing Enterobacteriaceae from blood cultures. Clin. Microbiol Infect. 20, 340\u2013344 (2014).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wan, Y. et al. Integrated analysis of patient networks and plasmid genomes to investigate a regional, multispecies outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes. J. Infect. Dis. 230, e159\u2013e170 (2024).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Lee, D. G. et al. Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial. Genome Biol. 7, R90 (2006).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Wiegand, I., Hilpert, K. & Hancock, R. E. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat. Protoc. 3, 163\u2013175 (2008).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Odds, F. C. Synergy, antagonism, and what the chequerboard puts between them. J. Antimicrob. Chemother. 52, 1 (2003).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Benn, G., Pyne, A. L. B., Ryadnov, M. G. & Hoogenboom, B. W. Imaging live bacteria at the nanoscale: comparison of immobilisation strategies. Analyst 144, 6944\u20136952 (2019).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n

Ne\u010das, D. & Klapetek, P. Gwyddion: an open-source software for SPM data analysis. Cent. Eur. J. Phys. 10, 181\u2013188 (2012).<\/p>\n


\n Google Scholar<\/a>\u00a0\n <\/p>\n

Buttress, J. A. et al. A guide for membrane potential measurements in Gram-negative bacteria using voltage-sensitive dyes. Microbiology https:\/\/doi.org\/10.1099\/mic.0.001227<\/a> (2022).<\/p>\n

Larrouy-Maumus, G., Clements, A., Filloux, A., McCarthy, R. R. & Mostowy, S. Direct detection of lipid A on intact Gram-negative bacteria by MALDI-TOF mass spectrometry. J. Microbiol. Methods 120, 68\u201371 (2016).<\/p>\n

Article<\/a>\u00a0
\n PubMed<\/a>\u00a0
\n PubMed Central<\/a>\u00a0
\n CAS<\/a>\u00a0
\n
\n Google Scholar<\/a>\u00a0\n <\/p>\n","protected":false},"excerpt":{"rendered":"Fanous, J. et al. Limited impact of Salmonella stress and persisters on antibiotic clearance. Nature https:\/\/doi.org\/10.1038\/s41586-024-08506-6 (2025). Article\u00a0…\n","protected":false},"author":2,"featured_media":169395,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[4414,53883,76405,59,3250,102,7925,6194,33193,33192,33194,56,54,55,181],"class_list":{"0":"post-169394","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-antibiotics","9":"tag-antimicrobial-resistance","10":"tag-bacterial-physiology","11":"tag-gb","12":"tag-general","13":"tag-health","14":"tag-infectious-diseases","15":"tag-life-sciences","16":"tag-medical-microbiology","17":"tag-microbiology","18":"tag-parasitology","19":"tag-uk","20":"tag-united-kingdom","21":"tag-unitedkingdom","22":"tag-virology"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/posts\/169394","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/comments?post=169394"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/posts\/169394\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/media\/169395"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/media?parent=169394"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/categories?post=169394"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/uk\/wp-json\/wp\/v2\/tags?post=169394"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}