Bioprospecting for Antibacterial Drugs: a Multidisciplinary Perspective on Natural Product Source Material, Bioassay Selection and Avoidable Pitfalls.

Bioprospecting is the exploration, extraction and screening of biological material and sometimes indigenous knowledge to discover and develop new drugs and other products. Most antibiotics in current clinical use (eg. ß-lactams, aminoglycosides, tetracyclines, macrolides) were discovered using this approach, and there are strong arguments to reprioritize bioprospecting over other strategies in the search for new antibacterial drugs. Academic institutions should be well positioned to lead the early stages of these efforts given their many thousands of locations globally and because they are not constrained by the same commercial considerations as industry. University groups can lack the full complement of knowledge and skills needed though (eg. how to tailor screening strategy to biological source material). In this article, we review three key aspects of the bioprospecting literature (source material and in vitro antibacterial and toxicity testing) and present an integrated multidisciplinary perspective on (a) source material selection, (b) legal, taxonomic and other issues related to source material, (c) cultivation methods, (d) bioassay selection, (e) technical standards available, (f) extract/compound dissolution, (g) use of minimum inhibitory concentration and selectivity index values to identify progressible extracts and compounds, and (h) avoidable pitfalls. The review closes with recommendations for future study design and information on subsequent steps in the bioprospecting process.

Comparative proteomics of Helicobacter species: the discrimination of gastric and enterohepatic Helicobacter species.

Helicobacter pylori is a major human pathogen that infects the gastric mucosa and is responsible for a range of infections including gastritis and gastric carcinoma. Although other bacteria within the Helicobacter genus can also infect the gastric mucosa, there are Helicobacter species that infect alternative sites within the gastrointestinal (GI) tract. Two-dimensional gel electrophoresis was used to compare the cellular proteomes of seven non-pylori Helicobacters (H. mustelae, H. felis, H. cinaedi, H. hepaticus, H. fennelliae, H. bilis and H. cholecystus) against the more extensively characterised H. pylori. The different Helicobacter species showed distinctive 2D protein profiles, it was possible to combine them into a single dataset using Progenesis SameSpots software. Principal Component Analysis was used to search for correlations between the bacterial proteomes and their sites of infection. This approach clearly discriminated between gastric (i.e. those which infect in the gastric mucosa) and enterohepatic Helicobacter species (i.e. those bacteria that infect the small intestine and hepatobillary regions of the GI tract). Selected protein spots showing significant differences in abundance between these two groups of bacteria were identified by LC-MS. The data provide an initial insight into defining those features of the bacterial proteome that influence the sites of bacterial infection. BIOLOGICAL SIGNIFICANCE: This study demonstrated that representative members of the Helicobacter genus were readily discriminated from each other on the basis of their in vitro whole cell proteomes determined using 2D gel electrophoresis. Despite the intra-species heterogeneity observed it was possible, to demonstrate that the enterohepatic (represented by H. bilis, H. hepaticus, H. fennelliae, H. cinaedi and H. cholecystus) and gastric (represented by H. pylori, H. mustelae, and H. felis) Helicobacters formed discrete groups based on their 2D protein profiles. A provisional proteomic signature was identified that correlated with the typical sites of colonisation of these members of the Helicobacter genus. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.