The Glox Discovery Platform has been developed from over 20 years of research into precision antimicrobials
Glox Therapeutics will exploit the reservoir of protein bacteriocins from Gram-negative bacteria to develop precision antibiotics that combat antimicrobial resistance. Our goal is to create potent, species-specific antibiotics that, unlike conventional antibiotics, do not harm the host microbiome. We will produce engineered bacteriocins based on platform technologies stemming from the Kleanthous (University of Oxford) and Walker (University of Glasgow) laboratories that are the foundation of Glox Therapeutics. The platform can be adapted to target any Gram-negative pathogens. The initial target organisms for Glox will be the pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae followed by Escherichia coli and Acinetobacter baumannii, all of which are on the WHO critical list of drug resistant bacteria for which new antibiotics are urgently required. Our initial target indication is ventilator-associated pneumonia which will be treated through intravenous delivery of bacteriocin constructs. Other acute pneumonias, bacteraemia, sepsis and chronic lung infection in patients with cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are additional indications that will be targeted.
Carpena N, Richards K, Bello Gonzalez TDJ, Bravo-Blas A, Housden NG, Gerasimidis K, Milling SWF, Douce G, Malik DJ, Walker D. (2021) Targeted delivery of narrow-spectrum protein antibiotics to the lower gastrointestinal tract in a murine model of Escherichia coli colonization. Front. Microbiol. 12, 670535.
Six A, Mosbahi K, Barge M, Kleanthous C, Evans T and Walker D (2021) Pyocin efficacy in a murine model of Pseudomonas aeruginosa sepsis. J. Antimicrob. Chemother. 76, 2317-2324.
Housden, N.G.‡, Webby, M.N. ‡, Lowe, E.D., El-Baba, T.J., Kaminska, R., Redfield, C., Robinson, C.V. & Kleanthous, C. (2021) Toxin import through the antibiotic efflux channel TolC. Nat. Commun. 12, 4625.
Behrens, H.M., Lowe, E.D., Gault, J., Housden, N.G., Kaminska, R., Weber, T.M., Thompson, C., Mislin, G.L.A., Walker, D., Robinson, C.V., Schalk, I.J. & Kleanthous, C. (2020) Pyocin S5 import into Pseudomonas aeruginosa reveals a generic mode of bacteriocin transport. mBio 11, e03230-19.
Atanaskovic, I., Mosbahi, K., Sharp, C., Housden, N.G., Kaminska, R., Walker, D. & Kleanthous, C. (2020) Targeted killing of Pseudomonas aeruginosa by pyocin G occurs via the hemin transporter Hur. J. Mol. Biol. 432, 3869-3880.
Francis, M.L.R.‡, Webby, M.N.‡, Housden, N.G., Kaminska, R., Elliston, E., Chinthammit, B., Lukoyanova, N. & Kleanthous, C. (2021) Porin threading drives receptor disengagement and establishes active colicin transport through Escherichia coli OmpF. EMBO J., e108610
Irvine S, Bunk B, Bayes HK, Spröer C, Connolly JPR, Six A, Evans TJ, Roe AJ, Overmann J and Walker D (2019) Genomic and transcriptomic characterisation of P. aeruginosa small colony variants derived from a chronic infection model. Microb. Genom. 5, e000262
Sharp, C., Boinnett, C., Cain, A., Kumar, S., Housden, N. G., Parkhill, J. & Kleanthous, C. (2019) O-antigen dependent colicin insensitivity of uropathogenic Escherichia coli. J. Bacteriol. 201, e00545-18.
Atanaskovic, I. & Kleanthous, C. (2019) Tools and approaches for dissecting bacteriocin import in Gram-negative bacteria. Frontiers in Microbiology 10, 646.
Mosbahi K, Wojnowska M, Albalat A and Walker D (2018) Bacterial iron acquisition mediated by outer membrane translocation and cleavage of a host protein. Proc. Natl. Acad. Sci. USA. 115: 6840-6845
Sharp, C., Bray, J., Maiden, M.C.* & Kleanthous, C.* (2017) Diversity and distribution of nuclease bacteriocins in bacterial genomes revealed by Hidden Markov Models. PLoS Comp Biol 13, e1005652.
White, P., Joshi, A., Rassam, P., Housden, N.G., Kaminska, R., Goult, J.D., Redfield, C., McCaughey, L.C., Walker, D., Mohammed, S. & Kleanthous, C. (2017) Exploitation of an iron transporter for bacterial protein antibiotic import. Proc. Natl. Acad. Sci. USA 114, 12051-12056.
Behrens, H., Six, A., Walker, D. & Kleanthous, C. (2017) Therapeutic potential of bacteriocins as protein antibiotics. Emerging Topics in Life Sciences 1, 65-74.
Housden, N.G., Hopper, J.T.S., Lukoyanova, N., Rodriguez-Larrea, D., Wojdyla, J.A., Klein, A., Kaminska, R., Bayley, H., Saibil, H.R., Robinson, C.V. & Kleanthous, C. (2013) Intrinsically disordered protein threads through the bacterial outer membrane porin OmpF. Science 340, 1570-1574.
Housden, N.G., Wojdyla, J.A., Korczynska, J., Grishkovskaya, I., Kirkpatrick, N., Brzozowski, A.M. & Kleanthous, C. (2010) Directed epitope delivery across the Escherichia coli outer membrane through the porin OmpF. Proc. Natl. Acad. Sci. USA 107, 21412-21417.