Abstract
Resistance-Nodulation-Cell Division (RND) pumps play important roles in bacterial resistance to antibiotics. Pseudomonas aeruginosa is an important human pathogen which exhibits high level resistance to antibiotics. There are total of 12 RND pumps present in the P. aeruginosa PAO1 genome. The recently characterized MuxABC-OpmB system has been shown to play a role in resistance to novobiocin, aztreonam, macrolides, and tetracycline in a multiple knockout mutation. In this study, we examined the expression levels of all the 12 RND pump gene clusters and tested the involvement of MuxABC-OpmB in pathogenicity. The results indicated that in addition to the four known constitutively expressed RND pumps, mexAB-oprM, mexGHIopmD, mexVW, and mexXY, relatively high levels of expression were observed with mexJK and muxABCopmB in the conditions tested. Inactivation of muxA in the muxABC-opmB operon resulted in elevated resistance to ampicillin and carbenicillin. The mutant also showed attenuated virulence in both Brassica rapa
pekinensis and Drosophila melanogaster infection models. The decreased virulence at least in part was due to decreased twitching motility in the mutant. These results indicate that the RND pump MuxABC-OpmB is associated with ampicillin and carbenicillin susceptibility and also involved in pathogenesis in P. aeruginosa.
Citations
Citations to this article as recorded by

- RND/HAE-1 members in the Pseudomonadota phylum: exploring multidrug resistance
Vinnícius Machado Schelk Gomes, Ana Carolina Silva Bulla, Pedro Henrique Monteiro Torres, Manuela Leal da Silva
Biophysical Reviews.2025; 17(2): 687. CrossRef - MexB‐Mediated Efflux Pumps in Pseudomonas aeruginosa: Mechanistic Insights, Inhibition Strategies, and Future Perspectives
Adarsha Sarmah, Neksha Shethia, Pooja Rao, S. L. Rath, Renitta Jobby, Jamuna Bai Aswathanarayan, Vinothkannan Ravichandran
ChemistrySelect.2025;[Epub] CrossRef - Efflux pumps of Pseudomonas aeruginosa and their regulatory mechanisms underlying multidrug resistance
Wen-Ru Li, Zhi-Qing Zhang, Kang Liao, Qing-Shan Shi, Xu-Bin Huang, Xiao-Bao Xie
International Biodeterioration & Biodegradation.2025; 202: 106096. CrossRef - Understanding Smog's impact on healthy male rat physiology: A multi-dimensional analysis
Muhammad Imran Khan, Arshia Amin, Wasim Sajjad, Yousef Abdullah M Bin Jardan
Heliyon.2025; 11(5): e42877. CrossRef - Challenges of quaternary ammonium antimicrobial agents: Mechanisms, resistance, persistence and impacts on the microecology
Jiaxin Zhang, Lei Cheng, Hao Li, Xi Chen, Lin Zhang, Tiantian Shan, Jiannan Wang, Ding Chen, Jiawei Shen, Xinxuan Zhou, Lichen Gou, Lixin Zhang, Xuedong Zhou, Biao Ren
Science of The Total Environment.2025; 958: 178020. CrossRef - Siderophores promote cooperative interspecies and intraspecies cross-protection against antibiotics in vitro
Anna Clara M. Galdino, Mylene Vaillancourt, Diana Celedonio, Kara Huse, Yohei Doi, Janet S. Lee, Peter Jorth
Nature Microbiology.2024; 9(3): 631. CrossRef - Assessment of antibiotic resistance genes in soils polluted by chemical and technogenic ways with poly-aromatic hydrocarbons and heavy metals
Ming Hung Wong, Tatiana Minkina, Nikita Vasilchenko, Svetlana Sushkova, Yanina Delegan, Anuj Ranjan, Pallavi Saxena, Sarieh Tarigholizadeh, Tamara Dudnikova, Andrey Barbashev, Aleksey Maksimov, Alexandr Faenson, Rıdvan Kızılkaya
Environmental Research.2024; 252: 118949. CrossRef - Distribution and Characterization of Quaternary Ammonium Biocides Resistant Bacteria in Different Soils, in South-Western China
Ziyi Guo, Cunli Qin, Lilan Zhang
Microorganisms.2024; 12(8): 1742. CrossRef - Developing antibiotics-based strategies to efficiently enrich ammonia-oxidizing archaea from wastewater treatment plants
Lai Peng, Mengwen Jia, Shengjun Li, Xi Wang, Chuanzhou Liang, Yifeng Xu
Science of The Total Environment.2024; 923: 171479. CrossRef - A brief update on the controversial and opposing roles of Pseudomonas aeruginosa efflux pumps in virulence regulation
Sheryl Erica Fernandes, Peter Jorth
Frontiers in Bacteriology.2023;[Epub] CrossRef - The balance between antibiotic resistance and fitness/virulence in Pseudomonas aeruginosa: an update on basic knowledge and fundamental research
Elena Jordana-Lluch, Isabel Mª Barceló, María Escobar-Salom, Miguel A. Estévez, Laura Zamorano, Silvia Gómez-Zorrilla, Elena Sendra, Antonio Oliver, Carlos Juan
Frontiers in Microbiology.2023;[Epub] CrossRef - Drug resistance and physiological roles of RND multidrug efflux pumps in Salmonella enterica, Escherichia coli and Pseudomonas aeruginosa
Seiji Yamasaki, Martijn Zwama, Tomohiro Yoneda, Mitsuko Hayashi-Nishino, Kunihiko Nishino
Microbiology
.2023;[Epub] CrossRef -
Antitoxin MqsA decreases antibiotic susceptibility through the global regulator AgtR in
Pseudomonas fluorescens
Si-Ping Zhang, Yi-Ping Ye, Jun Hou, Zi-Rui Ye, Zhi-Song Wang, Xiao-Quan Yu, Ding-Ding Guo, Yong Wang, Yong-Xing He, Laurent Poirel
Antimicrobial Agents and Chemotherapy.2023;[Epub] CrossRef - Metagenome meta-analysis reveals an increase in the abundance of some multidrug efflux pumps and mobile genetic elements in chemically polluted environments
Jessica Subirats, Hannah Sharpe, Vera Tai, Michael Fruci, Edward Topp, Christopher A. Elkins
Applied and Environmental Microbiology.2023;[Epub] CrossRef - Nutrient condition modulates the antibiotic tolerance of Pseudomonas aeruginosa
Huizhong Liu, Yingsi Wang, Zhiqing Zhang, Hong Qi, Yu Zhang, Wenru Li, Qingshan Shi, Xiaobao Xie
Science of The Total Environment.2023; 904: 166749. CrossRef - Making sense of drug-efflux transporters in the physiological environment
Helen I Zgurskaya, Justyna W Adamiak, Inga V Leus
Current Opinion in Microbiology.2022; 69: 102179. CrossRef - Pseudomonas aeruginosa efflux pump superfamily (review of literature)
Mikhail Eduardovich Ivanov, N. K. Fursova, V. D. Potapov
Russian Clinical Laboratory Diagnostics.2022; 67(1): 53. CrossRef - Effect of black pepper essential oil on quorum sensing and efflux pump systems in the fish-borne spoiler Pseudomonas psychrophila KM02 identified by RNA-seq, RT-qPCR and molecular docking analyses
Natalia Tomaś, Kamila Myszka, Łukasz Wolko, Katarzyna Nuc, Artur Szwengiel, Anna Grygier, Małgorzata Majcher
Food Control.2021; 130: 108284. CrossRef - Potential Therapeutic Targets for Combination Antibody Therapy against Pseudomonas aeruginosa Infections
Luke L. Proctor, Whitney L. Ward, Conner S. Roggy, Alexandra G. Koontz, Katie M. Clark, Alyssa P. Quinn, Meredith Schroeder, Amanda E. Brooks, James M. Small, Francina D. Towne, Benjamin D. Brooks
Antibiotics.2021; 10(12): 1530. CrossRef - Loss of RND-Type Multidrug Efflux Pumps Triggers Iron Starvation and Lipid A Modifications in Pseudomonas aeruginosa
Justyna W. Adamiak, Varsha Jhawar, Vincent Bonifay, Courtney E. Chandler, Inga V. Leus, Robert K. Ernst, Herbert P. Schweizer, Helen I. Zgurskaya
Antimicrobial Agents and Chemotherapy.2021;[Epub] CrossRef - Dynamic Adaptive Response of Pseudomonas aeruginosa to Clindamycin/Rifampicin-Impregnated Catheters
Kidon Sung, Jungwhan Chon, Ohgew Kweon, Seongwon Nho, Seongjae Kim, Miseon Park, Angel Paredes, Jin-Hee Lim, Saeed A. Khan, Kenneth Scott Phillips, Carl E. Cerniglia
Antibiotics.2021; 10(7): 752. CrossRef - Importance of twitching and surface-associated motility in the virulence of Acinetobacter baumannii
Jordi Corral, María Pérez-Varela, Miquel Sánchez-Osuna, Pilar Cortés, Jordi Barbé, Jesús Aranda
Virulence.2021; 12(1): 2201. CrossRef - A Screen for Antibiotic Resistance Determinants Reveals a Fitness Cost of the Flagellum in Pseudomonas aeruginosa
E. A. Rundell, N. Commodore, A. L. Goodman, B. I. Kazmierczak, Yves V. Brun
Journal of Bacteriology.2020;[Epub] CrossRef - Phylogenetic analysis reveals an ancient gene duplication as the origin of the MdtABC efflux pump
Kamil Górecki, Megan M. McEvoy, William M Shafer
PLOS ONE.2020; 15(2): e0228877. CrossRef - Two Component Regulatory Systems and Antibiotic Resistance in Gram-Negative Pathogens
Anjali Y. Bhagirath, Yanqi Li, Rakesh Patidar, Katherine Yerex, Xiaoxue Ma, Ayush Kumar, Kangmin Duan
International Journal of Molecular Sciences.2019; 20(7): 1781. CrossRef - Genomic and Transcriptomic Insights into How Bacteria Withstand High Concentrations of Benzalkonium Chloride Biocides
Minjae Kim, Janet K. Hatt, Michael R. Weigand, Raj Krishnan, Spyros G. Pavlostathis, Konstantinos T. Konstantinidis, Andrew J. McBain
Applied and Environmental Microbiology.2018;[Epub] CrossRef - Calcium induces tobramycin resistance in Pseudomonas aeruginosa by regulating RND efflux pumps
Sharmily Khanam, Manita Guragain, Dirk L. Lenaburg, Ryan Kubat, Marianna A. Patrauchan
Cell Calcium.2017; 61: 32. CrossRef - Cystic fibrosis lung environment and Pseudomonas aeruginosa infection
Anjali Y. Bhagirath, Yanqi Li, Deepti Somayajula, Maryam Dadashi, Sara Badr, Kangmin Duan
BMC Pulmonary Medicine.2016;[Epub] CrossRef - Multidrug-Resistance Transporter AbcA SecretesStaphylococcus aureusCytolytic Toxins
Hirono Yoshikai, Hayato Kizaki, Yuki Saito, Yosuke Omae, Kazuhisa Sekimizu, Chikara Kaito
Journal of Infectious Diseases.2016; 213(2): 295. CrossRef - Mechanism of coupling drug transport reactions located in two different membranes
Helen I. Zgurskaya, Jon W. Weeks, Abigail T. Ntreh, Logan M. Nickels, David Wolloscheck
Frontiers in Microbiology.2015;[Epub] CrossRef - The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria
Xian-Zhi Li, Patrick Plésiat, Hiroshi Nikaido
Clinical Microbiology Reviews.2015; 28(2): 337. CrossRef - Bacterial resistance mechanism: what proteomics can elucidate
Thais Bergamin Lima, Michelle Flaviane Soares Pinto, Suzana Meira Ribeiro, Loiane Alves Lima, Juliana Cançado Viana, Nelson Gomes Júnior, Elizabete Souza Cândido, Simoni Campos Dias, Octávio Luiz Franco
The FASEB Journal.2013; 27(4): 1291. CrossRef - Construction of a tightly-controlled expression system for use in Pseudomonas
Liang Yang, Lin Chen, Lixin Shen, Kangmin Duan
Biotechnology Letters.2013; 35(11): 1901. CrossRef - Resistance-Nodulation-Division Multidrug Efflux Pumps in Gram-Negative Bacteria: Role in Virulence
Dinesh Fernando, Ayush Kumar
Antibiotics.2013; 2(1): 163. CrossRef - Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World?
Alejandro Beceiro, María Tomás, Germán Bou
Clinical Microbiology Reviews.2013; 26(2): 185. CrossRef - The Drosophila melanogaster host model
Christina O. Igboin, Ann L. Griffen, Eugene J. Leys
Journal of Oral Microbiology.2012; 4(1): 10368. CrossRef - Role of the MexEF-OprN Efflux System in Low-Level Resistance of Pseudomonas aeruginosa to Ciprofloxacin
Catherine Llanes, Thilo Köhler, Isabelle Patry, Barbara Dehecq, Christian van Delden, Patrick Plésiat
Antimicrobial Agents and Chemotherapy.2011; 55(12): 5676. CrossRef