Novel approaches to developing new antibiotics for bacterial infections

Abstract

Antibiotics are an essential part of modern medicine. The emergence of antibiotic‐resistant mutants among bacteria is seemingly inevitable, and results, within a few decades, in decreased efficacy and withdrawal of the antibiotic from widespread usage. The traditional answer to this problem has been to introduce new antibiotics that kill the resistant mutants. Unfortunately, after more than 50 years of success, the pharmaceutical industry is now producing too few antibiotics, particularly against Gram‐negative organisms, to replace antibiotics that are no longer effective for many types of infection. This paper reviews possible new ways to discover novel antibiotics. The genomics route has proven to be target rich, but has not led to the introduction of a marketed antibiotic as yet. Non‐culturable bacteria may be an alternative source of new antibiotics. Bacteriophages have been shown to be antibacterial in animals, and may find use in specific infectious diseases. Developing new antibiotics that target non‐multiplying bacteria is another approach that may lead to drugs that reduce the emergence of antibiotic resistance and increase patient compliance by shortening the duration of antibiotic therapy. These new discovery routes have given rise to compounds that are in preclinical development, but, with one exception, have not yet entered clinical trials. For the time being, the majority of new antibiotics that reach the marketplace are likely to be structural analogues of existing families of antibiotics or new compounds, both natural and non‐natural which are screened in a conventional way against live multiplying bacteria. British Journal of Pharmacology (2007) 152, 1147–1154; doi:; published online 20 August 2007

Bioprospecting microbial natural product libraries from the marine environment for drug discovery

“…The analysis of DNA isolated from environmental samples has proved very useful for these bacteria, which may be a new source of novel antibiotics. [111][112][113] For example, metagenomes of sponge microbial communities have been shown to contain genes and gene clusters typical for the biosynthesis of biologically active natural products. 114 Heterologous expression approaches have also led to the isolation of secondary metabolism gene clusters from uncultured microbial symbionts of marine invertebrates, and soil metagenomic libraries.…”

Nitric oxide-releasing poly(lactic-co-glycolic acid)-polyethylenimine nanoparticles for prolonged nitric oxide release, antibacterial efficacy, and in vivo wound healing activity

“…The dorsal hair was shaved with an electric razor and the back skin was excised to create 5-mm diameter full-thickness wounds. Then, a suspension containing 6×10 8 MRSA US300…”

“…Owing to growing health care costs and increasing antibiotic resistance, the economic burden of the treatment of chronic wounds is rapidly growing. Considering that resistance against newly approved antibiotics develops within 2 years, 8 there is an urgent need for new generations of antibiotics to fight infections.…”

New perspectives on antibacterial drug research

“…Moreover, systemic use of phages for treating patients is likely to be immunogenic and may induce neutralizing antibodies. Apart from human therapy, bacteriophages have also been evaluated for use in the poultry and cattle industries, aquaculture and sewage treatment [80,81].…”