Antibacterial and antibiofilm potency of XF drugs, impact of photodynamic activation and synergy with antibiotics.

Board-Davies, Emma L., Rhys-Williams, William, Hynes, Daniel, Williams, David ORCID: https://orcid.org/0000-0002-7351-5131, Farnell, Damian J. ORCID: https://orcid.org/0000-0003-0662-1927 and Love, William 2022. Antibacterial and antibiofilm potency of XF drugs, impact of photodynamic activation and synergy with antibiotics. Frontiers in Cellular and Infection Microbiology 12 , 904465. 10.3389/fcimb.2022.904465

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Abstract

With increasing incidence of antimicrobial resistance, there is an urgent need for novel and effective antibacterials. Destiny Pharma plc have developed a series of porphyrin-based XF drugs, some with dual mechanisms of antibacterial action. An innate mechanism acts through binding to the outer bacterial membrane and a separate, light-activated, photodynamic (PD) mechanism, acts via the generation of reactive oxygen species. This study aimed to assess the innate and PD associated antibacterial activity of XF drugs against planktonic bacteria, their biofilms and combinational effects with conventional antibiotics. Minimum inhibitory concentrations (MICs) were determined for 3 XF drugs against 114 bacterial isolates. MICs for XF-73 and XF-70 were determined (± PD). DPD-207 was designed to not exhibit PD action due to its structure. XF-drugs (± PD) were further assessed for synergy with conventional antibiotics (using a checkerboard assay) and antibiofilm activity against susceptible strains. XF drugs were innately active against all tested Gram-positive isolates. PD action significantly increased bacterial susceptibility to XF-73 and XF-70 for all Gram-positive isolates. Generally, the XF drugs exhibited higher MICs against Gram-negative isolates, however PD significantly enhanced potency, particularly for XF-70. XF-73 and XF-70 exhibited synergy with ertapenem against a methicillin resistant Staphylococcus aureus (MRSA) strain (± PD) and XF-73 with polymyxin B (± PD) against Pseudomonas aeruginosa. No antagonism was seen between the XF drugs and any of the 5 antibiotics tested. The antibiofilm effect of XF drugs was also observed for all Staphylococcus isolates tested. Generally, PD did not enhance activity for other bacterial isolates tested with the exception of XF-73 against Acinetobacter baumannii biofilms. XF drugs exhibited significant antimicrobial activity against Gram-positive bacteria, with PD enhancement of bacterial susceptibility. Additionally, XF drugs displayed synergy with conventional antibiotics and demonstrated antibiofilm effects.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry
Additional Information:	This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Publisher:	Frontiers Media
ISSN:	2235-2988
Date of First Compliant Deposit:	5 July 2022
Date of Acceptance:	31 May 2022
Last Modified:	04 Jan 2024 08:37
URI:	https://orca.cardiff.ac.uk/id/eprint/151057

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