Secondary plant metabolites as potent drug candidates against antimicrobial-resistant pathogens

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Abstract

Antibiotic resistance is a major public health threat of the twenty-first century and represents an important risk to the global economy. Healthcare-associated infections mainly caused by drug-resistant bacteria are wreaking havoc in patient care worldwide. The spread of such pathogens limits the utility of available drugs and complicates the treatment of bacterial diseases. As a result, there is an urgent need for new drugs with mechanisms of action capable of curbing resistance. Plants synthesize and utilize various metabolic compounds to deter pathogens and predators. Utilizing these plant-based metabolites is a promising option in identifying novel bioactive compounds that could be harnessed to develop new potent antimicrobial drugs to treat multidrug-resistant pathogens. The purpose of this review is to highlight medicinal plants as important sources of novel antimicrobial agents that could be developed to help combat antimicrobial resistance.

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The antibiotic resistance crisis: part 1: causes and threats.

C Lee Ventola (2015)

Decades after the first patients were treated with antibiotics, bacterial infections have again become a threat because of the rapid emergence of resistant bacteria-a crisis attributed to abuse of these medications and a lack of new drug development.

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Mechanisms of Antibiotic Resistance.

Jose Munita, César Arias (2016)

Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic "attack" is the prime example of bacterial adaptation and the pinnacle of evolution. "Survival of the fittest" is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.

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Is Open Access

Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review

Mansura Mulani, Ekta E. Kamble, Shital N. Kumkar … (2019)

The acronym ESKAPE includes six nosocomial pathogens that exhibit multidrug resistance and virulence: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. Persistent use of antibiotics has provoked the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria, which render even the most effective drugs ineffective. Extended spectrum β-lactamase (ESBL) and carbapenemase producing Gram negative bacteria have emerged as an important therapeutic challenge. Development of novel therapeutics to treat drug resistant infections, especially those caused by ESKAPE pathogens is the need of the hour. Alternative therapies such as use of antibiotics in combination or with adjuvants, bacteriophages, antimicrobial peptides, nanoparticles, and photodynamic light therapy are widely reported. Many reviews published till date describe these therapies with respect to the various agents used, their dosage details and mechanism of action against MDR pathogens but very few have focused specifically on ESKAPE. The objective of this review is to describe the alternative therapies reported to treat ESKAPE infections, their advantages and limitations, potential application in vivo, and status in clinical trials. The review further highlights the importance of a combinatorial approach, wherein two or more therapies are used in combination in order to overcome their individual limitations, additional studies on which are warranted, before translating them into clinical practice. These advances could possibly give an alternate solution or extend the lifetime of current antimicrobials.

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Author and article information

Contributors

Charles Darkoh:

ORCID: http://orcid.org/0000-0003-0063-7856

Charles.Darkoh@uth.tmc.edu

Journal

Journal ID (nlm-ta): SN Appl Sci

Journal ID (iso-abbrev): SN Appl Sci

Title: Sn Applied Sciences

Publisher: Springer International Publishing (Cham )

ISSN (Print): 2523-3963

ISSN (Electronic): 2523-3971

Publication date (Electronic): 8 July 2022

Publication date PMC-release: 8 July 2022

Publication date (Print): 2022

Volume: 4

Issue: 8

Electronic Location Identifier: 209

Affiliations

[1 ]GRID grid.251973.b, ISNI 0000 0001 2151 1959, Biological & Environmental Sciences, , Alabama Agricultural & Mechanical University, ; Normal, AL 35762 USA

[2 ]GRID grid.267308.8, ISNI 0000 0000 9206 2401, Department of Epidemiology, School of Public Health, Center for Infectious Diseases, Human Genetics, and Environmental Sciences, , University of Texas Health Science Center, ; Houston, TX 77030 USA

[3 ]GRID grid.240145.6, ISNI 0000 0001 2291 4776, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Microbiology and Infectious Diseases Program, ; Houston, TX 77030 USA

Author information

Charles Darkoh http://orcid.org/0000-0003-0063-7856

Article

Publisher ID: 5084

DOI: 10.1007/s42452-022-05084-y

PMC ID: 9264742

PubMed ID: 35821909

SO-VID: a3942aaa-4181-4260-a4b3-b69daf624b83

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 6 March 2022

Date accepted : 20 June 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: R01AI116914

Award ID: R01AI150685

Award Recipient : Charles Darkoh

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Keywords: antimicrobial resistance,plant metabolites,plant secondary metabolites,multidrug-resistant pathogens,plant-based medical compounds,anti-infective agents,antibacterial drug screening

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Keywords: antimicrobial resistance, plant metabolites, plant secondary metabolites, multidrug-resistant pathogens, plant-based medical compounds, anti-infective agents, antibacterial drug screening

Secondary plant metabolites as potent drug candidates against antimicrobial-resistant pathogens

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Point-Of-Care Testing for AMR

Most cited references 98

The antibiotic resistance crisis: part 1: causes and threats.

Mechanisms of Antibiotic Resistance.

Emerging Strategies to Combat ESKAPE Pathogens in the Era of Antimicrobial Resistance: A Review

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