Microbial protein targets: towards understanding and intervention.

Paul W Denny

doi:10.1017/s0031182017002037

Abstract

The rise of antimicrobial resistance, coupled with a lack of industrial focus on antimicrobial discovery over preceding decades, has brought the world to a crisis point. With both human and animal health set to decline due to increased disease burdens caused by near untreatable microbial pathogens, there is an urgent need to identify new antimicrobials. Central to this is the elucidation of new, robustly validated, drug targets. Informed by industrial practice and concerns, the use of both biological and chemical tools in validation is key. In parallel, repurposing approved drugs for use as antimicrobials may provide both new treatments and identify new targets, whilst improved understanding of pharmacology will help develop and progress good 'hits' with the required rapidity. In recognition of the need to increase research efforts in these areas, in 14-16 September 2017, the British Society for Parasitology (BSP) Autumn Symposium was hosted at Durham University with the title: Microbial Protein Targets: towards understanding and intervention. Staged in collaboration with the Royal Society of Chemistry (RSC) Chemistry Biology Interface Division (CBID), the core aim was to bring together leading researchers working across disciplines to imagine novel approaches towards combating infection and antimicrobial resistance. Sessions were held on: 'Anti-infective discovery, an overview'; 'Omic approaches to target validation'; 'Genetic approaches to target validation'; 'Drug target structure and drug discovery'; 'Fragment-based approaches to drug discovery'; and 'Chemical approaches to target validation'. Here, we introduce a series of review and primary research articles from selected contributors to the Symposium, giving an overview of progress in understanding antimicrobial targets and developing new drugs. The Symposium was organized by Paul Denny (Durham) for the BSP and Patrick Steel (Durham) for RSC CBID.

Highlights

The threat posed by anti-microbial resistance (AMR) has been well publicized with respect to bacterial pathogens, and the need to identify, validate and exploit new drug targets emphasized (Brown and Wright, 2016)
The Special Issue of Parasitology introduced here is focused on global infectious disease, namely the causative agents of the bacterial disease tuberculosis (TB; Mycobacterium tuberculosis) and the protozoal infections malaria, toxoplasmosis, leishmaniasis, African Sleeping Sickness and Chagas disease
Remaining in the field of lipid biochemistry, protein acylation has long been proposed as a target of novel antiprotozoals, with the enzyme responsible for the essential N-myristoylation of proteins [N-myristoyl transferase (NMT)] identified as a potential drug target in apicomplexan (Gunaratne et al 2000) and kinetoplastid (Price et al 2003) protozoan parasites