BAC-SCREEN

BAC-SCREEN is a level 2 biosafety platform devoted to high-content screening (HCS) on whole-cell bacteria. The platform works at the chemistry-biology interface to develop new molecules that aim to define and address concerns related to antibiotic resistance. It is specialized in the discovery of inhibitors of antibiotic resistance mechanisms linked to the bacterial membrane and to the efflux pump systems.

BAC-SCREEN offers its skills and equipment to public and private research partnerships.

The platform’s operating mode enables it to offer different types of services:

• Complete services, from the technical study of the project to the analysis and interpretation of results.
• Access to facilities and equipments.
• Collaborative projects and partnerships.
• Training in the use of equipment and methodologies.

Resources And Equipments

Collection features

• 1 constantly evolving bacteria collection of Gram (+) and Gram (-) reference strains and clinical isolates of human and veterinary origin.
• 1 gallery of mutants overproducing resistance mechanisms associated with the bacterial wall (membrane impermeability, efflux pump) or mutated by deletion of the same mechanisms.
• 1 collection of membrane probes consisting of antibodies directed against proteins involved in antibiotic transport.
• 1 chemical library (~1000 molecules) originating from the MCT laboratory and augmented by external collaborations.

Automated chain

1 Freedom EVO 150 (Tecan) platform equipped with a multimode microplate reader Infinite M200 Pro (Tecan).

Analytical equipments

• 1 multimode microplate reader Infinite M200 Pro (Tecan) with automated reagent injection and temperature control for kinetic studies.
• 1 Spark® (Tecan) multimode microplate reader.
• 1 LC/MS system (Waters).
• 1 HPLC system (Agilent).

Bacterial culture

• 1 class II microbiological safety station (MSC Advantage™).
• Fixed and shaking incubators.
• Freezers (-80°C) for storing bacterial strains.
• 1 binocular magnifier and 1 STATIF Leica DM2000 LED microscope.

Approaches

Library screening

• Screening against BSL 2 pathogenic bacteria.
• Primary screening for Actives identification (« Hits »).
• Secondary screening and confirmation of Hits.

Antimicrobial and antibiofilms potenties of compounds (MIC, MBIC, MBEC, BPC)

• Standardized methods where available (CLSI, EUCAST) (CLSI, EUCAST).
• Detailed screening against broad panels of pathogens (susceptible & MDR bacteria with different resistance mechanisms & phenotypes).
• Bespoke methods developed for non-conventional drugs.

Phenotypic and target-based assays

• Phenotypic assays: growth inhibition of bacteria
• Up to 6 strains screened in a single run
• Gram positive bacteria (Staphylococcus aureus MRSA, Streptococcus, Enterococcus…)
• Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii Klebsiella spp …)

Medicinal chemistry and molecule design

• In silico analogue study & structure-activity relashionships (SAR)
• Chemical synthesis (specific cases)