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

Yannik K Schneider

doi:10.3390/antibiotics10070842

Yannik K Schneider

Open Access

https://doi.org/10.3390/antibiotics10070842

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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.

Highlights

Development of Antibiotic Resistance in Staphylococcus aureus
Myxobacterial genomes contain a high number of polyketide syntethases (PKS), non-ribosomal peptide synthetases (NRPS), and NRPS/PKS-hybrid gene clusters, and antibiotic compounds of the mentioned classes have been isolated from myxobacteria [85,86]
When it comes to natural products with strong pharmaceutical activities, they often turn out to be produced by bacteria

Summary

Introduction

Development of Antibiotic Resistance in Staphylococcus aureus. An Example for Acquisition of Resistance to Antibiotics in Clinical Use. Alexander Fleming warned already in 1945 that frequent and irresponsible use of antibiotics triggered by public demand would lead to a loss of efficacy [2] His statement that “microbes are educated to resist penicillin” was an early warning that deserved much more attention than it received. The development of new antibiotics in the first decades of the antibiotic era kept pace with the evolving development of resistance in an “arms race” with the pathogens. The first resistance against vancomycin and teicoplanin was reported in 1988 in Enterococcus faecium [10], and nearly one decade later, in 1997, an MRSA isolate from a wound infection exhibited decreased vancomycin susceptibility [11]. MRSA: Penicillin G (1), methicillin (2), vancomycin, (3), oxacillin (4) and teixobactin (5)

Mechanisms and Acquisition of Antibiotic Resistance

The Ancient Origin of Antibiotic Resistance

Suitability of Natural Products for Drug Discovery

Microorganisms as Producer of Natural Products and Hurdles in Bioprospecting

Findings

Conclusions