Pharmacology Discovery Services provides a robust portfolio of both in vitro potency and in vivo efficacy antimicrobial services to support the discovery and development of novel antimicrobials in our BSL-2 facility.

With a comprehensive collection of more than 850 clinically relevant Gram-positive and Gram-negative bacteria, including multi-drug resistant (MDR) organisms, anaerobic bacteria, yeast, and filamentous fungi, we provide in vitro antimicrobial services to help your drug development program succeed. Most strains are phenotyped, and the acquired antibiotic-resistance genes are genotyped. To accelerate your MIC testing, pre-designed panels are also available for fungal, bacterial, and N. gonorrhoeae. The minimum bactericidal concentration (MBC) may be determined following the M26-A guidelines of the Clinical and Laboratory Standards Institute.

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MIC Testing

The Minimum Inhibitory Concentration (MIC) testing from Pharmacology Discovery Services has over 850 strains of clinically relevant pathogens, including:

• Bacteria – aerobes and anaerobes
• Multidrug Resistant Strains (MDR) – E. coli, K. pneumoniae, N. gonorrhoeae, A. baumannii, P. aeruginosa, Enterococcus, Staphylococcus and Streptococcus
• Fungi – yeasts, molds and dermatophytes
• Characterization – most strains are phenotyped

To accelerate MIC testing off-the-shelf panels are available:

• Bacterial, Fungal, N. gonorrhoeae and ESKAPE pathogens
• Custom MIC panels - can be created with any of our available strains
• Minimum bactericidal concentration (MBC) - may be determined following the M26-A guidelines of the Clinical and Laboratory Standards Institute

Once MIC testing is complete we have a selection of other In vitro assays to further characterize antimicrobial compounds, including:

• Time Kill Assay – to determine if a compound has microbicidal properties
• Checkerboard Assay – to assess antimicrobial potency of two compounds alone and in combination
• Resistance Emergence – a group of custom assays to measure the frequency of resistance emergence
• Membrane Lysis Assay - to detect the disruption of S. aureus cell membrane
• Red Blood Lysis – to test if a compound can lyse human RBCs
• Cytotoxicity Assays - to measure cytotoxicity, 40 human and rodent cell lines are available

Publications

• A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy. Mango Z et al. Commun Biol. 2022 Nov;3:697. https://doi.org/10.1038/s42003-020-01420-3
• Rational design of balanced dual-targeting antibiotics with limited resistance. Nyerges A et al. PLoS Biol. 2020 Oct;18(10):e3000819. https://doi.org/10.1371/journal.pbio.3000819
• A dual-mechanism antibiotic kills gram-negative bacteria and avoids drug resistance. MARTIN II JK et al. Cell. 2020 Jun;181(7):1518-1532. https://doi.org/10.1016/j.cell.2020.05.005
• Potent LpxC Inhibitors with In vitro Activity against Multidrug-Resistant Pseudomonas aeruginosa. Krause KM et al. Antimicrob Agents Chemother. 2019 Oct;63(11):e00977-19. https://10.1128/AAC.00977-19. Print 2019 Nov.
• OG716: Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections. Kers JA et al. PLoS One. 2018 Jun ;13(6):e0197467. https://doi.org/10.1371/journal.pone.0197467
• In Vitro and In Vivo Efficacy of a Novel and Long-Acting Fungicidal Azole, PC1244, on Aspergillus fumigatus Infection. Colley T et al. Antimicrob Agents Chemother. 2018 Apr;62(5):e01941-17. https://doi.org/10.1128/AAC.01941-17
• Mutacin 1140 Lantibiotic Variants Are Efficacious Against Clostridium difficile Infection. Kers JA et al. Front. Microbiol. 2018 Mar;9:415. https://doi.org/10.3389/fmicb.2018.00415
• In Vivo Biomarker Analysis of the Effects of Intranasally Dosed PC945, a Novel Antifungal Triazole, on Aspergillus fumigatus Infection in Immunocompromised Mice. Kimura G et al. Antimicrobial agents and chemotherapy. 2017 Aug;61(9):e00124-17. https://doi.org/10.1128/AAC.00124-17
• Design and optimization of highly-selective, broad spectrum fungal CYP51 inhibitors. Yates CM et al. Bioorg Med Chem Lett. 2017 Aug;27(15):3243-3248. https://doi.org/10.1016/j.bmcl.2017.06.037
• In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection. Colley T et al. Antimicrob. Agents Chemother. 2017 Apr;61(5):e02280-16. https://doi.org/10.1128/AAC.02280-16