QUEX and UoE tackling antimicrobial resistance

Lapinska et al. (2022) Fast bacterial growth reduces antibiotic accumulation and efficacy. eLife 11:e74062

Microbes and Society network members at the University of Exeter have an established collaboration with the University of Queensland on antimicrobial resistance research, thanks to the successful QUEX partnership between the universities.

Associate Professor Stefano Pagliara (Biosciences), Professor Krasi Tsaneva-Atanasova (Mathematics), and Professor Mark Blaskovich (Chemistry – University of Queensland) started working together on antimicrobial resistance in 2018, via a QUEX Initiator grant. The grant allowed for initial mutual visits; this was followed by a QUEX accelerator grant, a QUEX PhD studentship, a £630k BBSRC grant, and, more recently, a £1.8m EPSRC Research Guarantee grant. The team has now grown, with a postdoctoral research associate, Dr Ula Lapinska, and a PhD student, Samuel Kraus.

The grants are enabling the team to investigate how antibiotic compounds enter bacteria. The team has discovered mechanisms that allow bacteria to resist and thus survive antibiotic treatment, and has been able to propose potential therapies to overcome such mechanisms.

Key researchers

Associate Professor Stefano Pagliara

Professor Krasi Tsaneva-Antasakova

Dr Ula Lapinska

Samuel Kraus, QUEX PhD student

Additional outputs

A growing number of publications have come from this long-running interdisciplinary partnership:

Zhang B, Phetsang W, Stone, M R L, Sanjaya Kc, Butler M S, Cooper M A, Elliott A G, Łapińska U, Voliotis M, Tsaneva-Anatasova K, Pagliara S, Blaskovich M A T (2023) Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage. Commun Biol 6, 409. https://doi.org/10.1038/s42003-023-04745-x

Kraus S, Łapińska U, Chawla K, Baker E, Attrill E L, O’Neill P, Farbos A, Jeffries A, Galyov E E, Korbsrisate S, Barnes K B, Harding S V, Tsaneva-Atanasova K, Blaskovich M A T, Pagliara S (2023) Phage-induced efflux down-regulation boosts antibiotic efficacy. bioRxiv https://doi.org/10.1101/2023.09.21.558807

Łapińska U, Voliotis M, Lee K K, Campey A, Stone M R L, Tuck B, Phetsang W, Zhang B, Tsaneva-Atanasova K, Blaskovich M A T, Pagliara S (2022) Fast bacterial growth reduces antibiotic accumulation and efficacy eLife 11:e74062. https://elifesciences.org/articles/74062

Conners, R, McLaren, M, Łapińska, U, Sanders K, Stone M R L, Blaskovich M A T, Pagliara S, Daum B, Rakonjac J, Gold V A M (2021) CryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage. Nat Commun 12, 6316 (2021). https://doi.org/10.1038/s41467-021-26610-3

Stone M R L, Łapińska U, Pagliara S, Masi M, Blanchfield J T, Cooper M A, Blaskovich M A T (2020) Fluorescent macrolide probes - synthesis and use in evaluation of bacterial resistance. RSC Chem. Biol., 1, 395-404. https://pubs.rsc.org/en/content/articlehtml/2020/cb/d0cb00118j