Bacterial Natural Product Drug Discovery for New Antibiotics: Strategies for Tackling the Problem of Antibiotic Resistance by Efficient Bioprospecting

Abstract

The problem of antibiotic resistance has become a challenge for our public health and society; it has allowed infectious diseases to re-emerge as a risk to human health. New antibiotics that are introduced to the market face the rise of resistant pathogens after a certain period of use. The relatively fast development of resistance against some antibiotics seems to be closely linked to their microbial origin and function in nature. Antibiotics in clinical use are merely products of microorganisms or derivatives of microbial products. The evolution of these antimicrobial compounds has progressed with the evolution of the respective resistance mechanisms in microbes for billions of years. Thus, antimicrobial resistance genes are present within the environment and can be taken up by pathogens through horizontal gene transfer. Natural products from bacteria are an important source of leads for drug development, and microbial natural products have contributed the most antibiotics in current clinical use. Bioprospecting for new antibiotics is a labor-intensive task as obstacles such as redetection of known compounds and low compound yields consume significant resources. The number of bacterial isolates one can theoretically investigate for new secondary metabolites is, on the other hand, immense. Therefore, the available capacity for biodiscovery should be focused on the most promising sources for chemical novelty and bioactivity, employing the appropriate scientific tools. This can be done by first looking into under- or unexplored environments for bacterial isolates and by focusing on the promising candidates to reduce the number of subjects.

Antimicrobial potentials of natural products against multidrug resistance pathogens: a comprehensive review

“…6 Globally, excessive use of antibiotics in animal husbandry and aquaculture, use of multiple broadspectrum agents, and lack of good antimicrobial stewardship can be listed as the factors mostly responsible for the spread of antibiotic resistance species. 7 The increase in the prevalence of antibiotic-resistant pathogens implies fewer antimicrobial agents to treat infections caused by these bacteria. 8 This raises consequently the need to search for alternative drugs or methods for controlling antibiotic-resistant pathogens.…”

Isolation and identification of endophytic actinobacteria from Citrullus colocynthis (L.) Schrad and their antibacterial properties

“…In addition, natural products provide key scaffolds for development of semi and synthetic drugs. The majority of antibiotics currently used in clinic are derived from microbes [ 9 , 10 ] which are either naturally occurring products or directly derived from such [ 7 ]. Among microbes, actinobacteria in particular Streptomyces , are responsible for suppling two-thirds of all known antibiotics utilized in modern medicine [ 11 , 12 ].…”

“…Microbial competition, nutritional status, and physical pressures from the natural habitat are all important factors in actinomycetes' development and antibiotic production [ 16 , 17 ]. Scientific literature evidenced that due to generating an unprecedented potential of bioactive compounds with diverse activities [ 18 ], actinobacteria have many pharmaceutical and medicinal functions [ 6 , 7 , 19 ]. This encourages researchers to search and screen under-explored or untapped habitats to isolate potential EA strains with antibacterial activities [ 20 , 21 ].…”

Analysis of the Distribution and Antibiotic Resistance of Pathogens Causing Infections in Hospitals from 2017 to 2019

“…ese included Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii, which, together with Enterobacter faecium as the [11]. ESKAPEE pathogens have developed resistance mechanisms against most antibiotic treatments, including those that are the last line of defense, such as carbapenems and polymyxins [12].…”