Plants as Latent Sources of New Antimicrobials and Resistance Modifying Agents Against Multi Drug Resistant ( MDR ) Strains (original) (raw)
Related papers
The problem of antibiotic resistance, which has limited the use of cheap and old antibiotics, has necessitated the need for a continued search for new antimicrobial compounds. Understanding the mechanisms of resistance is important in the development of strategies to solving the problem. Active efflux of drugs, alteration of target sites and enzymatic degradations are the strategies by which pathogenic bacteria acquire or develop intrinsic resistance to antibiotics. Multi-drug resistance (MDR) pumps, capable of recognizing and expelling a variety of structurally unrelated compounds from the bacterial cell and conferring resistance to a wide range of antibiotics have since been characterized in many gram positive and gram negative pathogens like Staphylococcus aureus , Pseudomonas aeruginosa , Escherichia coli and, more recently, in mycobacteria. The ability of some chemical compounds (called MDR inhibitors or resistance modifying agents) to modify the resistance phenotype in bacteri...
Journal of Antimicrobial Agents, 2018
The emergence of multiple drug resistant pathogenic bacteria has severely constricted the antimicrobial options of treating infectious diseases. One of the powerful mechanisms of antibacterial resistance employed by the antibiotic resistant bacteria is the active extrusion of antimicrobials with the help of membrane transporters known as efflux pumps. Efflux pumps effectively reduce the intracellular concentrations of antimicrobials by their antiporter activity in which antimicrobials are extruded outside the bacterial cell using energy derived from ionic gradient across the cell membrane. While a few efflux pumps are capable of conferring clinical levels of resistance to antibiotics, while many others only marginally increase the minimum inhibitory concentrations (MIC) of antibiotics. However, the role of efflux pumps in gradual development of antibiotic resistance by pathogenic bacteria due to mutations and other molecular mechanisms during the course of antimicrobial therapy is well recognized. The inhibition of active efflux can result in maintenance of an intracellular concentration of antibiotics necessary to inhibit or kill bacteria. Plant-derived compounds have historically been recognized as effective antimicrobial agents. Advances in analytical techniques have enabled purification of natural compounds responsible for efflux pump inhibition and these compounds and their derivatives can act as lead compounds for designing more effective efflux pump inhibitors. Efflux pump inhibition is promising as an effective method of confronting bacterial resistance to antimicrobials either alone or as adjuvants with antibiotics, and thereby restoring the antibacterial efficacy of antibiotics.
Plants as sources of new antimicrobials and resistance-modifying agents
Natural Product Reports, 2012
Infections caused by multidrug-resistant bacteria are an increasing problem due to the emergence and propagation of microbial drug resistance and the lack of development of new antimicrobials. Traditional methods of antibiotic discovery have failed to keep pace with the evolution of resistance. Therefore, new strategies to control bacterial infections are highly desirable. Plant secondary metabolites (phytochemicals) have already demonstrated their potential as antibacterials when used alone and as synergists or potentiators of other antibacterial agents. The use of phytochemical products and plant extracts as resistance-modifying agents (RMAs) represents an increasingly active research topic. Phytochemicals frequently act through different mechanisms than conventional antibiotics and could, therefore be of use in the treatment of resistant bacteria. The therapeutic utility of these products, however, remains to be clinically proven. The aim of this article is to review the advances in in vitro and in vivo studies on the potential chemotherapeutic value of phytochemical products and plant extracts as RMAs to restore the efficacy of antibiotics against resistant pathogenic bacteria. The mode of action of RMAs on the potentiation of antibiotics is also described. 7
Modern Phytomedicine, 2006
The use of the medicinal plants in the treatment of human diseases is an age-old practise in traditional systems of medicine throughout the world. Medicinal plants are an important source of diverse bioactive and therapeutic compounds, and the recent increase in the numbers of multidrug-resistant (MDR) bacteria has triggered immense interest in new drugs or preparations from natural sources, including plants. Particularly problematic groups of MDR bacteria include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), รข-lactamase-producing enteric bacteria (E. coli, Salmonella, Klebsiella, Shigella spp.) and other MDR Pseudomonas spp., Campylobacter spp., and Mycobacterium tuberculosis. Excessive and indiscriminate use of antibiotics has led to the development of such drug-resistant bacteria both in hospitals and communities all over the world.
Phytochemicals increase the antibacterial activity of antibiotics by acting on a drug efflux pump
MicrobiologyOpen, 2014
Drug efflux pumps confer resistance upon bacteria to a wide range of antibiotics from various classes. The expression of efflux pumps are also implicated in virulence and biofilm formation. Moreover, organisms can only acquire resistance in the presence of active drug efflux pumps. Therefore, efflux pump inhibitors (EPIs) are attractive compounds to reverse multidrug resistance and to prevent the development of resistance in clinically relevant bacterial pathogens. We investigated the potential of pure compounds isolated from plants to act as EPIs. In silico screening was used to predict the bioactivity of plant compounds and to compare that with the known EPI, phe-arg-b-naphthylamide (PAbN). Subsequently, promising products have been tested for their ability to inhibit efflux. Plumbagin nordihydroguaretic acid (NDGA) and to a lesser degree shikonin, acted as sensitizers of drug-resistant bacteria to currently used antibiotics and were able to inhibit the efflux pump-mediated removal of substrate from cells. We demonstrated the feasibility of in silico screening to identify compounds that potentiate the action of antibiotics against drug-resistant strains and which might be potentially useful lead compounds for an EPI discovery program.
Molecules, 2017
Multidrug resistance (MDR) has appeared in response to selective pressures resulting from the incorrect use of antibiotics and other antimicrobials. This inappropriate application and mismanagement of antibiotics have led to serious problems in the therapy of infectious diseases. Bacteria can develop resistance by various mechanisms and one of the most important factors resulting in MDR is efflux pump-mediated resistance. Because of the importance of the efflux-related multidrug resistance the development of new therapeutic approaches aiming to inhibit bacterial efflux pumps is a promising way to combat bacteria having over-expressed MDR efflux systems. The definition of an efflux pump inhibitor (EPI) includes the ability to render the bacterium increasingly more sensitive to a given antibiotic or even reverse the multidrug resistant phenotype. In the recent years numerous EPIs have been developed, although so far their clinical application has not yet been achieved due to their in vivo toxicity and side effects. In this review, we aim to give a short overview of efflux mediated resistance in bacteria, EPI compounds of plant and synthetic origin, and the possible methods to investigate and screen EPI compounds in bacterial systems.
New Hope in Microbial Multidrug Resistance
Community Acquired Infection
From the last some decades, microbial multidrug resistance (MDR) has developed one of the big treats in the many drug therapy. Due to this effect, so many sectors were get affected including the pharmaceutical sector, animal husbandry sector as well as in some way the agriculture sector too. There are so many mechanisms were developed by the microbes to developed resistance towards the medicines consisting of the development of degrading enzymes, structural modification in the microbes which is responsible to bind the drug, as well as last but not the least developing many effluxes pumps to push drug molecules outside of the microbial cell. Many studies demonstrated that lots of antibiotics and anticancer agents are majorly get affected by efflux pumps present on the cell wall. These mechanisms are observed in many common microbes including gram-positive and gram-negative microbes. As a result, efflux pumps are to be taken on top priority for the minimization of multidrug resistance...
Antibiotics
The unprecedented use of antibiotics that led to development of resistance affect human health worldwide. Prescription of antibiotics imprudently and irrationally in different diseases progressed with the acquisition and as such development of antibiotic resistant microbes that led to the resurgence of pathogenic strains harboring enhanced armors against existing therapeutics. Compromised the treatment regime of a broad range of antibiotics, rise in resistance has threatened human health and increased the treatment cost of diseases. Diverse on metabolic, genetic and physiological fronts, rapid progression of resistant microbes and the lack of a strategic management plan have led researchers to consider plant-derived substances (PDS) as alternative or in complementing antibiotics against the diseases. Considering the quantitative characteristics of plant constituents that attribute health beneficial effects, analytical procedures for their isolation, characterization and phytochemica...