Prospects for new antibiotics: a molecule-centered perspective

Abstract

There is a continuous need for iterative cycles of antibiotic discovery and development to deal with the selection of resistant pathogens that emerge as therapeutic application of an antibiotic becomes widespread. A short golden age of antibiotic discovery from nature followed by a subsequent golden half century of medicinal chemistry optimization of existing molecular scaffolds emphasizes the need for new antibiotic molecular frameworks. We bring a molecule-centered perspective to the questions of where will new scaffolds come from, when will chemogenetic approaches yield useful new antibiotics and what existing bacterial targets merit contemporary re-examination.

Antifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches

“…As has been shown and universally accepted within the antibacterial discovery community, in vitro-based high-throughput screening of individual antibacterial targets has been unsuccessful and is unlikely to provide a different outcome for antifungal lead discovery (Payne et al 2007). Rather, the traditionally successful "compound-centric" approach of empiric screening for small molecules with desirable whole cell bioactivity, cidal activity, and requisite spectrum against clinically relevant pathogens remains warranted (Roemer and Boone 2013;Walsh and Wencewicz 2013). However, combining this classic approach with genomics-era technologies that accelerate discovery time lines is essential.…”

Lewofloksacyna i moksyfloksacyna w leczeniu zakażeń bakteryjnych

“…Z tego powodu ich przydatność ograniczała się do leczenia zakażeń układu moczowego i chorób przenoszonych drogą płciową. Leki z tej grupy nie wykazywały aktywności przeciwko Pseudomonas aeruginosa, bakteriom Gram-dodatnim oraz beztlenowymi i były dostępne tylko w formie doustnej [5,6].…”

“…Ponieważ wykazywały one zdolność przechodzenia leku do wnętrza makrofagów płucnych, wykazano ich skuteczność skierowaną przeciwko bakteriom atypowym (Mycoplasma pneumoniae, Chlamydophila pneumoniae i Legionella pneumophila), a także wysoką aktywność przeciwko bakteriom Gram-ujemnym włącznie z Pseudomonas aeruginosa, przy niewielkiej aktywności przeciwko metycylinoopornym Staphylococcus aureus (ang. methicillin-resistant Staphylococcus aureus -MRSA) i braku aktywności przeciwko bakteriom Gram-dodatnim, w tym Streptococcus pneumoniae, oraz bakteriom beztlenowym [3,6].…”

The Future of Metabolomics and Individual Monitoring in Antimicrobial Therapy

“…In this way a interactome of resistome will be the basis for the development of new drugs and prevention of resistance emergence, as well as their evolution with the human holobiont [4,5]. In addition, functional metagenomics can monitor the appearance of resistance genes and spread of plasmid-borne in hosts and clinical environments [6].…”