Permeability Barrier of Gram-Negative Cell Envelopes and Approaches To Bypass ItClick to copy article linkArticle link copied!
Abstract
Gram-negative bacteria are intrinsically resistant to many antibiotics. Species that have acquired multidrug resistance and cause infections that are effectively untreatable present a serious threat to public health. The problem is broadly recognized and tackled at both the fundamental and applied levels. This paper summarizes current advances in understanding the molecular bases of the low permeability barrier of Gram-negative pathogens, which is the major obstacle in discovery and development of antibiotics effective against such pathogens. Gaps in knowledge and specific strategies to break this barrier and to achieve potent activities against difficult Gram-negative bacteria are also discussed.
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(21)
, 8310-8321. https://doi.org/10.1021/acs.jcim.4c01249
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(43)
, 13574-13582. https://doi.org/10.1021/acs.nanolett.4c03166
- Dominik Schum, Franziska A. V. Elsen, Stuart Ruddell, Kenji Schorpp, Howard Junca, Mathias Müsken, Shu-Yu Chen, Michaela K. Fiedler, Thomas Pickl, Dietmar H. Pieper, Kamyar Hadian, Martin Zacharias, Stephan A. Sieber. Screening Privileged Alkyl Guanidinium Motifs under Host-Mimicking Conditions Reveals a Novel Antibiotic with an Unconventional Mode of Action. JACS Au 2024, 4
(8)
, 3125-3134. https://doi.org/10.1021/jacsau.4c00449
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(22)
, 9151-9158. https://doi.org/10.1021/acs.analchem.4c00952
- Chuchu Guo, Kwo-Kwang A. Wang, Elizabeth M. Nolan. Investigation of Siderophore–Platinum(IV) Conjugates Reveals Differing Antibacterial Activity and DNA Damage Depending on the Platinum Cargo. ACS Infectious Diseases 2024, 10
(4)
, 1250-1266. https://doi.org/10.1021/acsinfecdis.3c00686
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(7)
, 1046-1056. https://doi.org/10.1021/acs.accounts.3c00814
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(12)
, 14385-14404. https://doi.org/10.1021/acsami.3c16490
- Rachel N. Motz, Chuchu Guo, Artur Sargun, Gregory T. Walker, Martina Sassone-Corsi, Manuela Raffatellu, Elizabeth M. Nolan. Conjugation to Native and Nonnative Triscatecholate Siderophores Enhances Delivery and Antibacterial Activity of a β-Lactam to Gram-Negative Bacterial Pathogens. Journal of the American Chemical Society 2024, 146
(11)
, 7708-7722. https://doi.org/10.1021/jacs.3c14490
- Santhni Subramaniam, Paul Joyce, Abiodun D. Ogunniyi, Admire Dube, Samantha L. Sampson, Claus-Michael Lehr, Clive A. Prestidge. Minimum Information for Conducting and Reporting In Vitro Intracellular Infection Assays. ACS Infectious Diseases 2024, 10
(2)
, 337-349. https://doi.org/10.1021/acsinfecdis.3c00613
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(5)
, 4478-4494. https://doi.org/10.1021/acsnano.3c11179
- Ana L. Santos, Dongdong Liu, Alexis van Venrooy, Jacob L. Beckham, Antonio Oliver, George P. Tegos, James M. Tour. Nonlethal Molecular Nanomachines Potentiate Antibiotic Activity Against Gram-Negative Bacteria by Increasing Cell Permeability and Attenuating Efflux. ACS Nano 2024, 18
(4)
, 3023-3042. https://doi.org/10.1021/acsnano.3c08041
- Alexis M. Stoorza, Adam S. Duerfeldt. Guiding the Way: Traditional Medicinal Chemistry Inspiration for Rational Gram-Negative Drug Design. Journal of Medicinal Chemistry 2024, 67
(1)
, 65-80. https://doi.org/10.1021/acs.jmedchem.3c01831
- Ruihao Yang, Haoran Zhang, Kang Sun, Congli Yuan, Ke Tao. Nano-Emulsified Perfluorooctyl Bromide Can Infiltrate Gram-Negative Bacteria and Sensitize Them to Ultrasound. Nano Letters 2024, 24
(1)
, 501-510. https://doi.org/10.1021/acs.nanolett.3c04545
- Pingxian Liu, Yunhan Jiang, Ling Jiao, Youfu Luo, Xiaodong Wang, Tao Yang. Strategies for the Discovery of Oxazolidinone Antibacterial Agents: Development and Future Perspectives. Journal of Medicinal Chemistry 2023, 66
(20)
, 13860-13873. https://doi.org/10.1021/acs.jmedchem.3c01040
- Danzel Marie Ramirez, Danyel Ramirez, Shiv Dhiman, Rajat Arora, Christian Lozeau, Gilbert Arthur, George Zhanel, Frank Schweizer. Guanidinylated Amphiphilic Tobramycin Derivatives Synergize with β-Lactam/β-Lactamase Inhibitor Combinations against Pseudomonas aeruginosa. ACS Infectious Diseases 2023, 9
(9)
, 1754-1768. https://doi.org/10.1021/acsinfecdis.3c00217
- Katie M. Kuo, Jinchan Liu, Anna Pavlova, James C. Gumbart. Drug Binding to BamA Targets Its Lateral Gate. The Journal of Physical Chemistry B 2023, 127
(34)
, 7509-7517. https://doi.org/10.1021/acs.jpcb.3c04501
- Samir Nandi, Karthika S. Nair, Harsha Bajaj. Bacterial Outer-Membrane-Mimicking Giant Unilamellar Vesicle Model for Detecting Antimicrobial Permeability. Langmuir 2023, 39
(16)
, 5891-5900. https://doi.org/10.1021/acs.langmuir.3c00378
- Do Young Kim, Suyeon Yeom, Jimin Park, Heeyeong Lee, Hak Joong Kim. Cytoplasmic Delivery of an Antibiotic, Trimethoprim, with a Simple Bidentate Catechol Analog as a Siderophore Mimetic. ACS Infectious Diseases 2023, 9
(3)
, 554-566. https://doi.org/10.1021/acsinfecdis.2c00556
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(2)
, 276-292. https://doi.org/10.1021/jacsau.2c00532
- Ziwei Hu, Inga V. Leus, Brinda Chandar, Bradley S. Sherborne, Quentin P. Avila, Valentin V. Rybenkov, Helen I. Zgurskaya, Adam S. Duerfeldt. Structure–Uptake Relationship Studies of Oxazolidinones in Gram-Negative ESKAPE Pathogens. Journal of Medicinal Chemistry 2022, 65
(20)
, 14144-14179. https://doi.org/10.1021/acs.jmedchem.2c01349
- Rebeka C. Fanti, Stanley N. S. Vasconcelos, Carolina M. C. Catta-Preta, Jaryd R. Sullivan, Gustavo P. Riboldi, Caio V. dos Reis, Priscila Z. Ramos, Aled M. Edwards, Marcel A. Behr, Rafael M. Couñago. A Target Engagement Assay to Assess Uptake, Potency, and Retention of Antibiotics in Living Bacteria. ACS Infectious Diseases 2022, 8
(8)
, 1449-1467. https://doi.org/10.1021/acsinfecdis.2c00073
- Karan Bali, Zeinab Mohamed, Anna Scheeder, Anna-Maria Pappa, Susan Daniel, Clemens F. Kaminski, Róisín M. Owens, Ioanna Mela. Nanoscale Features of Tunable Bacterial Outer Membrane Models Revealed by Correlative Microscopy. Langmuir 2022, 38
(29)
, 8773-8782. https://doi.org/10.1021/acs.langmuir.2c00628
- Joshua D. Shirley, Kelsie M. Nauta, Erin E. Carlson. Live-Cell Profiling of Penicillin-Binding Protein Inhibitors in Escherichia coli MG1655. ACS Infectious Diseases 2022, 8
(7)
, 1241-1252. https://doi.org/10.1021/acsinfecdis.2c00004
- Dominik Gurvic, Andrew G. Leach, Ulrich Zachariae. Data-Driven Derivation of Molecular Substructures That Enhance Drug Activity in Gram-Negative Bacteria. Journal of Medicinal Chemistry 2022, 65
(8)
, 6088-6099. https://doi.org/10.1021/acs.jmedchem.1c01984
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(2)
, 284-291. https://doi.org/10.1021/acsmedchemlett.1c00648
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(12)
, 2719-2730. https://doi.org/10.1021/acschembio.1c00572
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(12)
, 3345-3354. https://doi.org/10.1021/acsinfecdis.1c00501
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(13)
, 5256-5260. https://doi.org/10.1021/acs.orglett.1c01786
- Peter J. F. Henderson, Claire Maher, Liam D. H. Elbourne, Bart A. Eijkelkamp, Ian T. Paulsen, Karl A. Hassan. Physiological Functions of Bacterial “Multidrug” Efflux Pumps. Chemical Reviews 2021, 121
(9)
, 5417-5478. https://doi.org/10.1021/acs.chemrev.0c01226
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(5)
, 1827-1835. https://doi.org/10.1021/acsbiomaterials.0c01271
- Pedro D. Manrique, S. Gnanakaran. Microscopic Approach to Intrinsic Antibiotic Resistance. The Journal of Physical Chemistry B 2021, 125
(12)
, 3114-3118. https://doi.org/10.1021/acs.jpcb.1c00607
- Qicai Xiao, Bingjie Mai, Yichu Nie, Chuang Yuan, Menghua Xiang, Zihan Shi, Juan Wu, Wingnang Leung, Chuanshan Xu, Shao Q. Yao, Pan Wang, Liqian Gao. In Vitro and In Vivo Demonstration of Ultraefficient and Broad-Spectrum Antibacterial Agents for Photodynamic Antibacterial Chemotherapy. ACS Applied Materials & Interfaces 2021, 13
(10)
, 11588-11596. https://doi.org/10.1021/acsami.0c20837
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(2)
, 735-742. https://doi.org/10.1021/acs.molpharmaceut.0c00820
- Vadim Baidin, Tristan W. Owens, Michael B. Lazarus, Daniel Kahne. Simple Secondary Amines Inhibit Growth of Gram-Negative Bacteria through Highly Selective Binding to Phenylalanyl-tRNA Synthetase. Journal of the American Chemical Society 2021, 143
(2)
, 623-627. https://doi.org/10.1021/jacs.0c11113
- Pham Thu Phuong, Susan Oliver, Junchen He, Edgar H. H. Wong, Robert T. Mathers, Cyrille Boyer. Effect of Hydrophobic Groups on Antimicrobial and Hemolytic Activity: Developing a Predictive Tool for Ternary Antimicrobial Polymers. Biomacromolecules 2020, 21
(12)
, 5241-5255. https://doi.org/10.1021/acs.biomac.0c01320
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(23)
, 14937-14950. https://doi.org/10.1021/acs.jmedchem.0c01506
- Sol R. Martínez, Andrés M. Durantini, María C. Becerra, Gonzalo Cosa. Real-Time Single-Cell Imaging Reveals Accelerating Lipid Peroxyl Radical Formation in Escherichia coli Triggered by a Fluoroquinolone Antibiotic. ACS Infectious Diseases 2020, 6
(9)
, 2468-2477. https://doi.org/10.1021/acsinfecdis.0c00317
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(34)
, 37834-37844. https://doi.org/10.1021/acsami.0c06501
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(14)
, 7773-7816. https://doi.org/10.1021/acs.jmedchem.0c00347
- Rachael A. Mansbach, Inga V. Leus, Jitender Mehla, Cesar A. Lopez, John K. Walker, Valentin V. Rybenkov, Nicolas W. Hengartner, Helen I. Zgurskaya, S. Gnanakaran. Machine Learning Algorithm Identifies an Antibiotic Vocabulary for Permeating Gram-Negative Bacteria. Journal of Chemical Information and Modeling 2020, 60
(6)
, 2838-2847. https://doi.org/10.1021/acs.jcim.0c00352
- Stephen E. Motika, Rebecca J. Ulrich, Emily J. Geddes, Hyang Yeon Lee, Gee W. Lau, Paul J. Hergenrother. Gram-Negative Antibiotic Active Through Inhibition of an Essential Riboswitch. Journal of the American Chemical Society 2020, 142
(24)
, 10856-10862. https://doi.org/10.1021/jacs.0c04427
- Doris Mia Taylor, Justin Anglin, Suhyeorn Park, Melek N. Ucisik, John C. Faver, Nicholas Simmons, Zhuang Jin, Murugesan Palaniappan, Pranavanand Nyshadham, Feng Li, James Campbell, Liya Hu, Banumathi Sankaran, B. V. Venkataram Prasad, Hongbing Huang, Martin M. Matzuk, Timothy Palzkill. Identifying Oxacillinase-48 Carbapenemase Inhibitors Using DNA-Encoded Chemical Libraries. ACS Infectious Diseases 2020, 6
(5)
, 1214-1227. https://doi.org/10.1021/acsinfecdis.0c00015
- Samuel A. Juliano, Leonardo F. Serafim, Searle S. Duay, Maria Heredia Chavez, Gaurav Sharma, Mary Rooney, Fatih Comert, Scott Pierce, Andrei Radulescu, Myriam L. Cotten, Mihaela Mihailescu, Eric R. May, Alexander I. Greenwood, Rajeev Prabhakar, Alfredo M. Angeles-Boza. A Potent Host Defense Peptide Triggers DNA Damage and Is Active against Multidrug-Resistant Gram-Negative Pathogens. ACS Infectious Diseases 2020, 6
(5)
, 1250-1263. https://doi.org/10.1021/acsinfecdis.0c00051
- Anh K. Lam, Hannah Panlilio, Jennifer Pusavat, Cassandra L. Wouters, Erika L. Moen, Charles V. Rice. Overcoming Multidrug Resistance and Biofilms of Pseudomonas aeruginosa with a Single Dual-Function Potentiator of β-Lactams. ACS Infectious Diseases 2020, 6
(5)
, 1085-1097. https://doi.org/10.1021/acsinfecdis.9b00486
- Paramita Saha, Samapan Sikdar, Ganesh Krishnamoorthy, Helen I. Zgurskaya, Valentin V. Rybenkov. Drug Permeation against Efflux by Two Transporters. ACS Infectious Diseases 2020, 6
(4)
, 747-758. https://doi.org/10.1021/acsinfecdis.9b00510
- Soojeung Kim, Haeun Lee, Woon Young Song, Hak Joong Kim. Total Syntheses of Fimsbactin A and B and Their Stereoisomers to Probe the Stereoselectivity of the Fimsbactin Uptake Machinery in Acinetobacter baumannii. Organic Letters 2020, 22
(7)
, 2806-2810. https://doi.org/10.1021/acs.orglett.0c00790
- Mohini Mohan Konai, Jayanta Haldar. Lysine-Based Small Molecule Sensitizes Rifampicin and Tetracycline against Multidrug-Resistant Acinetobacter baumannii and Pseudomonas aeruginosa. ACS Infectious Diseases 2020, 6
(1)
, 91-99. https://doi.org/10.1021/acsinfecdis.9b00221
- Xuan Xin, Mengmeng Zhang, Xiao-Feng Li, Guanglei Zhao. Biocatalytic Synthesis of Lipophilic Baicalin Derivatives as Antimicrobial Agents. Journal of Agricultural and Food Chemistry 2019, 67
(42)
, 11684-11693. https://doi.org/10.1021/acs.jafc.9b04667
- Anindita Gayen, Deepak Kumar, Saravanan Matheshwaran, Manabendra Chandra. Unveiling the Modulating Role of Extracellular pH in Permeation and Accumulation of Small Molecules in Subcellular Compartments of Gram-negative Escherichia coli using Nonlinear Spectroscopy. Analytical Chemistry 2019, 91
(12)
, 7662-7671. https://doi.org/10.1021/acs.analchem.9b00574
- Hans Prochnow, Verena Fetz, Sven-Kevin Hotop, Mariel A. García-Rivera, Axel Heumann, Mark Brönstrup. Subcellular Quantification of Uptake in Gram-Negative Bacteria. Analytical Chemistry 2019, 91
(3)
, 1863-1872. https://doi.org/10.1021/acs.analchem.8b03586
- Vern L. Schramm. Enzymatic Transition States and Drug Design. Chemical Reviews 2018, 118
(22)
, 11194-11258. https://doi.org/10.1021/acs.chemrev.8b00369
- Carolina Pasero, Ilaria D’Agostino, Filomena De Luca, Claudio Zamperini, Davide Deodato, Giuseppina I. Truglio, Filomena Sannio, Rosita Del Prete, Teresa Ferraro, Daniela Visaggio, Arianna Mancini, Mario B. Guglielmi, Paolo Visca, Jean-Denis Docquier, Maurizio Botta. Alkyl-guanidine Compounds as Potent Broad-Spectrum Antibacterial Agents: Chemical Library Extension and Biological Characterization. Journal of Medicinal Chemistry 2018, 61
(20)
, 9162-9176. https://doi.org/10.1021/acs.jmedchem.8b00619
- Haeun Lee, Woon Young Song, Minju Kim, Min Wook Lee, Soojeung Kim, Ye Song Park, Kyungwon Kwak, Man Hwan Oh, Hak Joong Kim. Synthesis and Characterization of Anguibactin To Reveal Its Competence To Function as a Thermally Stable Surrogate Siderophore for a Gram-Negative Pathogen, Acinetobacter baumannii. Organic Letters 2018, 20
(20)
, 6476-6479. https://doi.org/10.1021/acs.orglett.8b02789
- Florian Graef, Robert Richter, Verena Fetz, Xabier Murgia, Chiara De Rossi, Nicole Schneider-Daum, Giuseppe Allegretta, Walid Elgaher, Jörg Haupenthal, Martin Empting, Felix Beckmann, Mark Brönstrup, Rolf Hartmann, Sarah Gordon, Claus-Michael Lehr. In Vitro Model of the Gram-Negative Bacterial Cell Envelope for Investigation of Anti-Infective Permeation Kinetics. ACS Infectious Diseases 2018, 4
(8)
, 1188-1196. https://doi.org/10.1021/acsinfecdis.7b00165
- Connor J. Cooper, Ganesh Krishnamoorthy, David Wolloscheck, John K. Walker, Valentin V. Rybenkov, Jerry M. Parks, Helen I. Zgurskaya. Molecular Properties That Define the Activities of Antibiotics in Escherichia coli and Pseudomonas aeruginosa. ACS Infectious Diseases 2018, 4
(8)
, 1223-1234. https://doi.org/10.1021/acsinfecdis.8b00036
- Robert J. Moreau, Colin K. Skepper, Brent A. Appleton, Anke Blechschmidt, Carl J. Balibar, Bret M. Benton, Joseph E. Drumm, III, Brian Y. Feng, Mei Geng, Cindy Li, Mika K. Lindvall, Andreas Lingel, Yipin Lu, Mulugeta Mamo, Wosenu Mergo, Valery Polyakov, Thomas M. Smith, Kenneth Takeoka, Kyoko Uehara, Lisha Wang, Jun-Rong Wei, Andrew H. Weiss, Lili Xie, Wenjian Xu, Qiong Zhang, Javier de Vicente. Fragment-Based Drug Discovery of Inhibitors of Phosphopantetheine Adenylyltransferase from Gram-Negative Bacteria. Journal of Medicinal Chemistry 2018, 61
(8)
, 3309-3324. https://doi.org/10.1021/acs.jmedchem.7b01691
- Colin K. Skepper, Robert J. Moreau, Brent A. Appleton, Bret M. Benton, Joseph E. Drumm, III, Brian Y. Feng, Mei Geng, Cheng Hu, Cindy Li, Andreas Lingel, Yipin Lu, Mulugeta Mamo, Wosenu Mergo, Mina Mostafavi, Christopher M. Rath, Micah Steffek, Kenneth T. Takeoka, Kyoko Uehara, Lisha Wang, Jun-Rong Wei, Lili Xie, Wenjian Xu, Qiong Zhang, Javier de Vicente. Discovery and Optimization of Phosphopantetheine Adenylyltransferase Inhibitors with Gram-Negative Antibacterial Activity. Journal of Medicinal Chemistry 2018, 61
(8)
, 3325-3349. https://doi.org/10.1021/acs.jmedchem.7b01861
- David Wolloscheck, Ganesh Krishnamoorthy, Jennifer Nguyen, and Helen I. Zgurskaya . Kinetic Control of Quorum Sensing in Pseudomonas aeruginosa by Multidrug Efflux Pumps. ACS Infectious Diseases 2018, 4
(2)
, 185-195. https://doi.org/10.1021/acsinfecdis.7b00160
- Jessica L Alexander, Zhen Yu, and J. A Cowan . Amino Terminal Copper and Nickel Binding Motif Derivatives of Ovispirin-3 Display Increased Antimicrobial Activity via Lipid Oxidation. Journal of Medicinal Chemistry 2017, 60
(24)
, 10047-10055. https://doi.org/10.1021/acs.jmedchem.7b01117
- Erin P. McCauley, Hanh Lam, Nicholas Lorig-Roach, Justin Luu, Cameron Lloyd, Karen Tenney, Halina Pietraszkiewicz, Cristina Diaz, Frederick A. Valeriote, Victoria Auerbuch, and Phillip Crews . Investigation of the Physical and Bioactive Properties of Bromo- and Iodo-Containing Sponge-Derived Compounds Possessing an Oxyphenylethanamine Core. Journal of Natural Products 2017, 80
(12)
, 3255-3266. https://doi.org/10.1021/acs.jnatprod.7b00694
- Chee Wei Ang, Angie M. Jarrad, Matthew A. Cooper, and Mark A. T. Blaskovich . Nitroimidazoles: Molecular Fireworks That Combat a Broad Spectrum of Infectious Diseases. Journal of Medicinal Chemistry 2017, 60
(18)
, 7636-7657. https://doi.org/10.1021/acs.jmedchem.7b00143
- Manuka Ghosh, Patricia A. Miller, Ute Möllmann, William D. Claypool, Valerie A. Schroeder, William R. Wolter, Mark Suckow, Honglin Yu, Shuang Li, Weiqiang Huang, Jaroslav Zajicek, and Marvin J. Miller . Targeted Antibiotic Delivery: Selective Siderophore Conjugation with Daptomycin Confers Potent Activity against Multidrug Resistant Acinetobacter baumannii Both in Vitro and in Vivo. Journal of Medicinal Chemistry 2017, 60
(11)
, 4577-4583. https://doi.org/10.1021/acs.jmedchem.7b00102
- Jean-Philippe Surivet, Cornelia Zumbrunn, Thierry Bruyère, Daniel Bur, Christopher Kohl, Hans H. Locher, Peter Seiler, Eric A. Ertel, Patrick Hess, Michel Enderlin-Paput, Stéphanie Enderlin-Paput, Jean-Christophe Gauvin, Azely Mirre, Christian Hubschwerlen, Daniel Ritz, and Georg Rueedi . Synthesis and Characterization of Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Antibacterial Activity against Gram-Negative Bacteria. Journal of Medicinal Chemistry 2017, 60
(9)
, 3776-3794. https://doi.org/10.1021/acs.jmedchem.6b01831
- Ramkumar Iyer, Mark A. Sylvester, Camilo Velez-Vega, Ruben Tommasi, Thomas F. Durand-Reville, and Alita A. Miller . Whole-Cell-Based Assay To Evaluate Structure Permeation Relationships for Carbapenem Passage through the Pseudomonas aeruginosa Porin OprD. ACS Infectious Diseases 2017, 3
(4)
, 310-319. https://doi.org/10.1021/acsinfecdis.6b00197
- Venkateswarlu Yarlagadda, Goutham B. Manjunath, Paramita Sarkar, Padma Akkapeddi, Krishnamoorthy Paramanandham, Bibek R. Shome, Raju Ravikumar, and Jayanta Haldar . Glycopeptide Antibiotic To Overcome the Intrinsic Resistance of Gram-Negative Bacteria. ACS Infectious Diseases 2016, 2
(2)
, 132-139. https://doi.org/10.1021/acsinfecdis.5b00114
- Maya A Farha, Megan M Tu, Eric D Brown. Important challenges to finding new leads for new antibiotics. Current Opinion in Microbiology 2025, 83 , 102562. https://doi.org/10.1016/j.mib.2024.102562
- Alessandra M. Martorana, Paola Sperandeo, Alessandra Polissi. How to fight bacteria without inducing drug resistance?. 2025, 247-280. https://doi.org/10.1016/B978-0-12-823994-0.00001-3
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- Daniel Palberg, Emma Kaszecki, Chetan Dhanjal, Anna Kisiała, Erin N. Morrison, Naomi Stock, R. J. Neil Emery. Impact of glyphosate and glyphosate-based herbicides on phyllospheric Methylobacterium. BMC Plant Biology 2024, 24
(1)
https://doi.org/10.1186/s12870-024-04818-x
- Dominik Gurvic, Ulrich Zachariae. Multidrug efflux in Gram-negative bacteria: structural modifications in active compounds leading to efflux pump avoidance. npj Antimicrobials and Resistance 2024, 2
(1)
https://doi.org/10.1038/s44259-024-00023-w
- Pedro D. Manrique, Inga V. Leus, César A. López, Jitender Mehla, Giuliano Malloci, Silvia Gervasoni, Attilio V. Vargiu, Rama K. Kinthada, Liam Herndon, Nicolas W. Hengartner, John K. Walker, Valentin V. Rybenkov, Paolo Ruggerone, Helen I. Zgurskaya, S. Gnanakaran. Predicting permeation of compounds across the outer membrane of P. aeruginosa using molecular descriptors. Communications Chemistry 2024, 7
(1)
https://doi.org/10.1038/s42004-024-01161-y
- Kamal el Battioui, Sohini Chakraborty, András Wacha, Dániel Molnár, Mayra Quemé-Peña, Imola Cs. Szigyártó, Csenge Lilla Szabó, Andrea Bodor, Kata Horváti, Gergő Gyulai, Szilvia Bősze, Judith Mihály, Bálint Jezsó, Loránd Románszki, Judit Tóth, Zoltán Varga, István Mándity, Tünde Juhász, Tamás Beke-Somfai. In situ captured antibacterial action of membrane-incising peptide lamellae. Nature Communications 2024, 15
(1)
https://doi.org/10.1038/s41467-024-47708-4
- Cristina Elías-López, Montserrat Muñoz-Rosa, Julia Guzmán-Puche, Elena Pérez-Nadales, Eduardo Chicano-Galvez, Luis Martínez-Martínez. Porin expression in clinical isolates of Klebsiella pneumoniae: a comparison of SDS-PAGE and MALDI-TOF/MS and limitations of whole genome sequencing analysis. Annals of Clinical Microbiology and Antimicrobials 2024, 23
(1)
https://doi.org/10.1186/s12941-024-00761-9
- Md Aquib, Wenting Yang, Luofeng Yu, Vinod Kumar Kannaujiya, Yuhao Zhang, Peng Li, Andrew Whittaker, Changkui Fu, Cyrille Boyer. Effect of cyclic topology
versus
linear terpolymers on antibacterial activity and biocompatibility: antimicrobial peptide avatars. Chemical Science 2024, 15
(45)
, 19057-19069. https://doi.org/10.1039/D4SC05797J
- Zhao Xia, Hao Xiang, Yi‐Ming Shi. Bacterial Secondary Metabolites Embedded in Producer Cell Membranes and Antibiotics Targeting Their Biosynthesis. ChemMedChem 2024, 37 https://doi.org/10.1002/cmdc.202400469
- Zeinab Raoufi, Sajad Abdollahi. Vaccination with OprB porin, and its epitopes offers protection against A. baumannii infections in mice. International Immunopharmacology 2024, 141 , 112972. https://doi.org/10.1016/j.intimp.2024.112972
- Nadia T. A. Dawoud, Hamada El‐Gendi, Doaa R. Lotfy, Esmail M. El‐Fakharany, Magda H. Abdellattif. Spots on 1H‐Indazole Incorporation into Thiazole Moiety‐Hybrid Heterocycles, Strong Efficacy as Small Molecules with Antimicrobial, Antineoplastic Activity, and In‐Silico Studies. ChemistrySelect 2024, 9
(40)
https://doi.org/10.1002/slct.202402828
- Jiumei Hu, Liben Chen, Pengfei Zhang, Fan‐En Chen, Hui Li, Kuangwen Hsieh, Sixuan Li, Johan H. Melendez, Tza‐Huei Wang. Exploiting β‐Lactams‐Induced Lysis and DNA Fragmentation for Rapid Molecular Antimicrobial Susceptibility Testing of
Neisseria Gonorrhoeae
via Dual‐Digital PCR. Advanced Science 2024, 10 https://doi.org/10.1002/advs.202405272
- Rachel Bargabos, Akira Iinishi, Bryson Hawkins, Thomas Privalsky, Norman Pitt, Sangkeun Son, Rachel Corsetti, Michael F. Gates, Ryan D. Miller, Kim Lewis, . Small molecule produced by
Photorhabdus
interferes with ubiquinone biosynthesis in Gram-negative bacteria. mBio 2024, 15
(10)
https://doi.org/10.1128/mbio.01167-24
- Eric M. Kofoed, Ignacio Aliagas, Terry Crawford, Jialin Mao, Seth F. Harris, Min Xu, Shumei Wang, Ping Wu, Fang Ma, Kevin Clark, Jessica Sims, Yiming Xu, Yutian Peng, Elizabeth Skippington, Ying Yang, Janina Reeder, Savita Ubhayakar, Matt Baumgardner, Zhengyin Yan, Jacob Chen, Summer Park, Hua Zhang, Chun-Wan Yen, Maria Lorenzo, Nicholas Skelton, Xiaorong Liang, Liuxi Chen, Bridget Hoag, Chun Sing Li, Zhiguo Liu, John Wai, Xingrong Liu, Jun Liang, Man Wah Tan, . Discovery of GuaB inhibitors with efficacy against
Acinetobacter baumannii
infection. mBio 2024, 15
(10)
https://doi.org/10.1128/mbio.00897-24
- Rodah C. Soy, Balaji Babu, John Mack, Tebello Nyokong. Photodynamic anticancer and antibacterial properties of a series of Sn(IV) tetraarylporphyrins. Journal of Porphyrins and Phthalocyanines 2024, 28
(09n10)
, 601-617. https://doi.org/10.1142/S1088424624500275
- William Best, Maya Ferrell, Andrew Boris, Neda Heydarian, Hannah Panlilio, Charles V. Rice. Acquisition of Resistance to PEGylated Branched Polyethylenimine Increases
Pseudomonas Aeruginosa
Susceptibility to Aminoglycosides. ChemMedChem 2024, 19
(17)
https://doi.org/10.1002/cmdc.202300689
- Haiyan Fan, Kanat Dukenbayev, Lazzat Nurtay, Faisal Nazir, Nurgul Daniyeva, Tri T. Pham, Enrico Benassi. Mechanism of the antimicrobial activity induced by phosphatase inhibitor sodium ortho-vanadate. Journal of Inorganic Biochemistry 2024, 258 , 112619. https://doi.org/10.1016/j.jinorgbio.2024.112619
- Cezara Bucataru, Corina Ciobanasu. Antimicrobial peptides: Opportunities and challenges in overcoming resistance. Microbiological Research 2024, 286 , 127822. https://doi.org/10.1016/j.micres.2024.127822
- Okan Yildirim, Dipti Barman, Mia Chung, Samantha Stone, Raphael Geißen, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan. Design and synthesis of a library of C8-substituted sulfamidoadenosines to probe bacterial permeability. Bioorganic & Medicinal Chemistry Letters 2024, 110 , 129844. https://doi.org/10.1016/j.bmcl.2024.129844
- Rachael Nilson, Swathi Penumutchu, Francesco S. Pagano, Peter Belenky, . Metabolic changes associated with polysaccharide utilization reduce susceptibility to some β-lactams in
Bacteroides thetaiotaomicron. mSphere 2024, 9
(8)
https://doi.org/10.1128/msphere.00103-24
- Ayesha Firdose, Toshinari Maeda, Mohd Asif Mohd Sukri, Nazlina Haiza Mohd Yasin, Noramiza Sabturani, Wan Syaidatul Aqma. Antibacterial mechanism of Pseudomonas aeruginosa UKMP14T rhamnolipids against multidrug resistant Acinetobacter baumannii. Microbial Pathogenesis 2024, 193 , 106743. https://doi.org/10.1016/j.micpath.2024.106743
- Pawan Kumar, Rohit Bhatia, Naresh Kumar Rangra. Scaffolds imparting anthelmintic activity: recent advancements and SAR studies. Molecular Diversity 2024, 9 https://doi.org/10.1007/s11030-024-10869-x
- Justyna W. Adamiak, Laiba Ajmal, Helen I. Zgurskaya, . Non-interchangeable functions of efflux transporters of
Pseudomonas aeruginosa
in survival under infection-associated stress. Journal of Bacteriology 2024, 206
(7)
https://doi.org/10.1128/jb.00054-24
- Rodah C. Soy, Donovan Mafukidze, John Mack, Tebello Nyokong. The Photodynamic Antibacterial Activity Properties of a Series of Indium(III) Porphyrins and their Gold and Silver Nanoparticle Conjugates. European Journal of Inorganic Chemistry 2024, 27
(20)
https://doi.org/10.1002/ejic.202400072
- Mohamed E.I. Badawy, Kareem E.E. Esmaiel, Mai M. Badr, Saad R. El-Zemity. Synthesis, antimicrobial, antioxidant and molecular docking studies of novel multifunctional chloroacetamide derivatives. Analytical Chemistry Letters 2024, 14
(4)
, 458-498. https://doi.org/10.1080/22297928.2024.2396323
- Rodah C. Soy, Pertunia R. Macigane, John Mack, Tebello Nyokong. Photodynamic antibacterial chemotherapy activities of P(V) and Ga(III) triarylcorroles and their silver nanoparticle conjugates. Journal of Porphyrins and Phthalocyanines 2024, 28
(07)
, 469-486. https://doi.org/10.1142/S1088424624500408
- Tarosha Salpadoru, Kevin E. Pinks, Jacob A. Lieberman, Kaitlyn Cotton, Karen L. Wozniak, Nikolay Gerasimchuk, Marianna A. Patrauchan, . Novel antimony-based antimicrobial drug targets membranes of Gram-positive and Gram-negative bacterial pathogens. Microbiology Spectrum 2024, 12
(6)
https://doi.org/10.1128/spectrum.04234-23
- Magdalena Metzger, Stefan Manhartseder, Leonie Krausgruber, Lea Scholze, David Fuchs, Carina Wagner, Michaela Stainer, Johannes Grillari, Andreas Kubin, Lionel Wightman, Peter Dungel. The Multifaceted Actions of PVP–Curcumin for Treating Infections. International Journal of Molecular Sciences 2024, 25
(11)
, 6140. https://doi.org/10.3390/ijms25116140
- Mohamad Azmeer Hissam, Zainab Ngaini, Nor Hisam Zamakshshari, Fatin Nur Amira Mohammad Hejemi, Fatin Salihah Arni, Ainaa Nadiah Abd Halim. Synthesis and molecular docking simulation on the antimicrobial effects of halogenated vanillin-azo dyes and schiff base derivatives. Discover Applied Sciences 2024, 6
(6)
https://doi.org/10.1007/s42452-024-05830-4
- Aldo S. de Oliveira, Arthur R. Cenci, Lucas Gonçalves, Maria Eduarda C. Thedy, Angelica Justino, Antônio L. Braga, Lidiane Meier. Chalcone Derivatives as Antibacterial Agents: An Updated Overview. Current Medicinal Chemistry 2024, 31
(17)
, 2314-2329. https://doi.org/10.2174/0929867330666230220140819
- Divyapriya Karthikeyan, Sanjit Kumar, N.S. Jayaprakash. A comprehensive review of recent developments in the gram-negative bacterial UDP-2,3-diacylglucosamine hydrolase (LpxH) enzyme. International Journal of Biological Macromolecules 2024, 267 , 131327. https://doi.org/10.1016/j.ijbiomac.2024.131327
- Andrew M. Hogan, Anna Motnenko, A. S. M. Zisanur Rahman, Silvia T. Cardona, . Cell envelope structural and functional contributions to antibiotic resistance in
Burkholderia cenocepacia. Journal of Bacteriology 2024, 206
(4)
https://doi.org/10.1128/jb.00441-23
- Danzel Marie Ramirez, Shiv Dhiman, Ayan Mukherjee, Ruwani Wimalasekara, Frank Schweizer. Application of tobramycin benzyl ether as an antibiotic adjuvant capable of sensitizing multidrug-resistant Gram-negative bacteria to rifampicin. RSC Medicinal Chemistry 2024, 15
(3)
, 1055-1065. https://doi.org/10.1039/D3MD00602F
- Surajit Bhattacharjya, Zhizhuo Zhang, Ayyalusamy Ramamoorthy. LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases. Biomolecules 2024, 14
(3)
, 320. https://doi.org/10.3390/biom14030320
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