Bacterial Drug Efflux Pump Inhibitors from Plants

Seukep, Armel Jackson; Fokoua-Maxime, Christophe Dongmo; Mbuntcha, Hélène Gueaba; Chen, Guilin; Assob, Jules Clément Nguedia; Tenniswood, Martin; Sarker, Satyajit Dey; Kuete, Victor; Ming-Quan, Guo

doi:10.1007/978-981-16-3120-7_16

Armel Jackson Seukep^5,6,7,8,
Christophe Dongmo Fokoua-Maxime^9,10,
Hélène Gueaba Mbuntcha¹¹,
Guilin Chen^6,7,8,
Jules Clément Nguedia Assob⁵,
Martin Tenniswood¹²,
Satyajit Dey Sarker¹³,
Victor Kuete¹¹ &
…
Guo Ming-Quan^6,7,8

1458 Accesses
1 Citations

Abstract

The current global antimicrobial resistance (AMR) crisis is a serious hazard to public health, food security, and development. Drug-resistant pathogens diminish the effectiveness of conventional antibiotics, thereby leading to frequent therapeutic failures and reducing the available antibiotic armory. There is an increasing risk of therapeutic impasse if no action is taken now. Novel resistance modalities are appearing within bacterial species and disseminating worldwide, undermining our ability to cure common infectious diseases. Among the identified resistance strategies developed by bacteria, efflux pump systems (EPs) are widely acknowledged as the main mechanism leading to multidrug resistance (MDR). MDR is concomitant with the overexpression of the transporters (EPs) that identify and pump out from the cell a large array of structurally dissimilar compounds. The antibiotic pipeline is narrow, and the paucity of novel antimicrobial therapeutics in development is a growing concern. The inhibition of EPs in bacteria appears as a successful alternative in the fight against AMR. Indeed, efflux pump inhibitors (EPIs) offer considerable promise as therapeutic agents, under the hypothesis that they would increase the intracellular concentration of standard antibiotics and hence restore their antimicrobial activity. Considering the cellular toxicity of known synthetic EPIs, investigations are increasingly directed towards the discovery of naturally occurring agents. Plant-derived compounds are found as one of the most dependable sources of safe EPIs. In recent years, a plethora of plant-derived EPIs have been described, although so far, no compound has yet passed all the stages of drug development. The difficulties in developing plant-derived EPI drugs are ascribed to the complexity of EPs, the structural and functional requirements of EPIs, and their cellular toxicity and side effects. In this chapter, we emphasize the roles of EPs in multidrug resistance, describe the major plant-based EPIs, and lay out the challenges impeding the development of plant-derived EPI drugs.

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Abbreviations

ABC:: Adenosine triphosphate (ATP)-binding cassette
AMR:: Antimicrobial resistance
EPIs:: Efflux pump inhibitors
EPs:: Efflux pump systems
EtBr:: Ethidium bromide
MATE:: Multidrug and toxic extrusion
MDR:: Multidrug resistance
MFS:: Major facilitator superfamily
PACE:: Proteobacterial antimicrobial compound efflux
PDR:: Pandrug resistant
RND:: Resistance-nodulation-cell division
SMR:: Small multidrug resistance
XDR:: Extensively drug resistant

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Department of Biomedical Sciences, Faculty of Health Sciences, University of Buea, Buea, Cameroon
Armel Jackson Seukep & Jules Clément Nguedia Assob
CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan, China
Armel Jackson Seukep, Guilin Chen & Guo Ming-Quan
Sino-Africa Joint Research Center, Chinese Academy of Sciences, Wuhan, China
Armel Jackson Seukep, Guilin Chen & Guo Ming-Quan
Innovation Academy for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai, China
Armel Jackson Seukep, Guilin Chen & Guo Ming-Quan
Department of Epidemiology and Biostatistics, University of New York State - University at Albany School of Public Health, Albany, NY, USA
Christophe Dongmo Fokoua-Maxime
New York State Department of Health, Albany, NY, USA
Christophe Dongmo Fokoua-Maxime
Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon
Hélène Gueaba Mbuntcha & Victor Kuete
Cancer Research Center, University of New York State - University at Albany, Rensselaer, NY, USA
Martin Tenniswood
Centre for Natural Products Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
Satyajit Dey Sarker

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Seukep, A.J. et al. (2022). Bacterial Drug Efflux Pump Inhibitors from Plants. In: Kumar, V., Shriram, V., Paul, A., Thakur, M. (eds) Antimicrobial Resistance. Springer, Singapore. https://doi.org/10.1007/978-981-16-3120-7_16

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