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- Pioneering strategies for overcoming bacterial drug resistance (2026)
- Advancing microbial engineering through synthetic biology (2025)
- Host-associated microbiome (2024)
- Bacterial regulatory mechanisms for the control of complex cellular mechanisms (2023)
- Two years into COVID-19 pandemic: Where are we? (2022)
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- From resistance mechanisms to therapy: Antimicrobial resistance in Gram-negative bacteria
- Minho Lee
- Received April 20, 2026 Accepted June 5, 2026 Published online August 6, 2026
- DOI: https://doi.org/10.71150/jm.2604017 [Epub ahead of print]
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- 3 Download
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Abstract
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Supplementary Material -
Antimicrobial resistance poses a major global health challenge, and infections caused by multidrug-resistant Gram-negative bacteria are associated with substantial morbidity and mortality. In contrast to many Gram-positive pathogens, Gram-negative bacteria combine intrinsic barriers with acquired determinants, including enzymatic drug inactivation, reduced outer membrane permeability, active efflux, and target modifications, which collectively compromise the efficacy of multiple antibiotic classes. Previous reviews have largely catalogued resistant pathogens or antimicrobial agents. This review provides a mechanism-focused overview of antimicrobial resistance in clinically important Gram-negative bacteria and explains how dominant resistance determinants translate into clinically relevant failure modes, such as delayed effective therapy, limited treatment options, and increased reliance on toxic last-line agents. Current and emerging therapeutic strategies are discussed through a mechanism-based lens, emphasizing newer β-lactam/β-lactamase inhibitor combinations and nontraditional approaches, including phages, antivirulence, and microbiome-based interventions. This review highlights the conceptual links between resistance mechanisms, clinical impact, and rational therapeutic choices and identifies priorities for future research aimed at mitigating antimicrobial-resistant Gram-negative infections.
- Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening
- Soo Min Kim , Iliana Escorbar , Kiho Lee , Beth Burgwyn Fuchs , Eleftherios Mylonakis , Wooseong Kim
- J. Microbiol. 2020;58(6):431-444. Published online May 27, 2020
- DOI: https://doi.org/10.1007/s12275-020-0163-8
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- 10 Web of Science
- 11 Crossref
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Abstract
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- Staphylococcus aureus is a leading cause of hospital- and community- acquired infections. Despite current advances in antimicrobial chemotherapy, the infections caused by S. aureus remain challenging due to their ability to readily develop resistance. Indeed, antibiotic resistance, exemplified by methicillin- resistant S. aureus (MRSA) is a top threat to global health security. Furthermore, the current rate of antibiotic discovery is much slower than the rate of antibiotic-resistance development. It seems evident that the conventional in vitro bacterial growth-based screening strategies can no longer effectively supply new antibiotics at the rate needed to combat bacterial antibiotic-resistance. To overcome this antibiotic resistance crisis, screening assays based on host–pathogen interactions have been developed. In particular, the free-living nematode Caenorhabditis elegans has been used for drug screening against MRSA. In this review, we will discuss the general principles of the C. elegans-based screening platform and will highlight its unique strengths by comparing it with conventional antibiotic screening platforms. We will outline major hits from high-throughput screens of more than 100,000 small molecules using the C. elegans–MRSA infection assay and will review the mode-of-action of the identified hit compounds. Lastly, we will discuss the potential of a C. elegansbased screening strategy as a paradigm shift screening platform.
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Citations
Citations to this article as recorded by
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Advances in methicillin-resistant
Staphylococcus aureus
drug discovery: developments and challenges
Stephanos Vassilopoulos, Eleftherios Mylonakis
Expert Opinion on Drug Discovery.2026; 21(2): 231. CrossRef - Investigation of anti-aging and anti-infection properties of Jingfang Granules using the Caenorhabditis elegans model
Xin Yin, Yiwei Meng, Chenghong Sun, Yanqiu Zhao, Weitao Wang, Peipei Zhao, Mengmeng Wang, Jingli Ren, Jingchun Yao, Lixin Zhang, Xuekui Xia
Biogerontology.2024; 25(3): 433. CrossRef - PHPGAT: predicting phage hosts based on multimodal heterogeneous knowledge graph with graph attention network
Fu Liu, Zhimiao Zhao, Yun Liu
Briefings in Bioinformatics.2024;[Epub] CrossRef - Alternatives to animal models to study bacterial infections
Chengming Hu, Wenlong Yang
Folia Microbiologica.2023; 68(5): 703. CrossRef - Gold nanoparticle-DNA aptamer-assisted delivery of antimicrobial peptide effectively inhibits Acinetobacter baumannii infection in mice
Jaeyeong Park, Eunkyoung Shin, Ji-Hyun Yeom, Younkyung Choi, Minju Joo, Minho Lee, Je Hyeong Kim, Jeehyeon Bae, Kangseok Lee
Journal of Microbiology.2022; 60(1): 128. CrossRef - Antimicrobial activity of the membrane-active compound nTZDpa is enhanced at low pH
Soo Min Kim, Guijin Zou, Hyerim Kim, Minjeong Kang, Soyeon Ahn, Hee Young Heo, Jae-Seok Kim, Kyung-Min Lim, Frederick M. Ausubel, Eleftherios Mylonakis, Huajian Gao, Wooseong Kim
Biomedicine & Pharmacotherapy.2022; 150: 112977. CrossRef - Antibiotic resistant bacteria: current situation and treatment options to accelerate the development of a new antimicrobial arsenal
Antonio Tarín-Pelló, Beatriz Suay-García, María-Teresa Pérez-Gracia
Expert Review of Anti-infective Therapy.2022; 20(8): 1095. CrossRef - Therapeutic potentials of endophytes for healthcare sustainability
Ayodeji O. Falade, Kayode E. Adewole, Temitope C. Ekundayo
Egyptian Journal of Basic and Applied Sciences.2021; 8(1): 117. CrossRef -
Novel Immune Modulators Enhance
Caenorhabditis elegans
Resistance to Multiple Pathogens
Nicholas A. Hummell, Alexey V. Revtovich, Natalia V. Kirienko, Paul Dunman
mSphere.2021;[Epub] CrossRef - Caenorhabditis elegans, a Host to Investigate the Probiotic Properties of Beneficial Microorganisms
Cyril Poupet, Christophe Chassard, Adrien Nivoliez, Stéphanie Bornes
Frontiers in Nutrition.2020;[Epub] CrossRef - New Antimicrobial Bioactivity against Multidrug-Resistant Gram-Positive Bacteria of Kinase Inhibitor IMD0354
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Antibiotics.2020; 9(10): 665. CrossRef
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Advances in methicillin-resistant
Staphylococcus aureus
drug discovery: developments and challenges
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