Insights into antibiotic resistance promoted by quinolone exposure.

Quinolone-induced antibiotic resistance (QIAR) refers to the phenomenon by which bacteria exposed to sublethal levels of quinolones acquire resistance to non-quinolone antibiotics. We have explored this in MG1655 using a variety of compounds and bacteria carrying a quinolone-resistance mutation in gyrase, mutations affecting the SOS response, and mutations in error-prone polymerases. The nature of the antibiotic-resistance mutations was determined by whole-genome sequencing.

Expression Atlas update: gene and protein expression in multiple species.

The EMBL-EBI Expression Atlas is an added value knowledge base that enables researchers to answer the question of where (tissue, organism part, developmental stage, cell type) and under which conditions (disease, treatment, gender, etc) a gene or protein of interest is expressed. Expression Atlas brings together data from >4500 expression studies from >65 different species, across different conditions and tissues. It makes these data freely available in an easy to visualise form, after expert curation to accurately represent the intended experimental design, re-analysed via standardised pipelines that rely on open-source community developed tools.

Quinolones: Mechanism, Lethality and Their Contributions to Antibiotic Resistance.

Fluoroquinolones (FQs) are arguably among the most successful antibiotics of recent times. They have enjoyed over 30 years of clinical usage and become essential tools in the armoury of clinical treatments. FQs target the bacterial enzymes DNA gyrase and DNA topoisomerase IV, where they stabilise a covalent enzyme-DNA complex in which the DNA is cleaved in both strands.

Predictive modeling targets thymidylate synthase ThyX in Mycobacterium tuberculosis.

There is an urgent need to identify new treatments for tuberculosis (TB), a major infectious disease caused by Mycobacterium tuberculosis (Mtb), which results in 1.5 million deaths each year. We have targeted two essential enzymes in this organism that are promising for antibacterial therapy and reported to be inhibited by naphthoquinones.

DNA Topoisomerases.

DNA topoisomerases are enzymes that control the topology of DNA in all cells. There are two types, I and II, classified according to whether they make transient single- or double-stranded breaks in DNA. Their reactions generally involve the passage of a single- or double-strand segment of DNA through this transient break, stabilized by DNA-protein covalent bonds.

Lead selection and characterization of antitubercular compounds using the Nested Chemical Library.

Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find novel antitubercular agents several approaches have been used in various institutions worldwide, including target-based approaches against several validated mycobacterial enzymes and phenotypic screens. We screened more than 17,000 compounds from Vichem's Nested Chemical Library™ using an integrated strategy involving whole cell-based assays with Corynebacterium glutamicum and Mycobacterium tuberculosis, and target-based assays with protein kinases PknA, PknB and PknG as well as other targets such as PimA and bacterial topoisomerases simultaneously.