Antimicrobial Efficacy of XF-73 and Photo-Activated XF-73 Against Clinically Relevant Microorganisms in Planktonic and Biofilm Mode of Growth

Abstract

Novel antimicrobials are urgently needed to combat the global increase in antimicrobial resistance. Exeporfinium chloride (XF-73) is a synthetic dicationic porphyrin antimicrobial, acting through membrane disruption; with a secondary mechanism of action, activated via blue light exposure. The aim of this study was to assess the antimicrobial efficacy of XF-73 and photo-activated XF-73 against a panel of clinically relevant Gram-positive and Gram-negative microorganisms in planktonic and biofilm modes of growth. The antimicrobial efficacy of XF-73 was assessed through minimum inhibitory and bactericidal concentration (MIC/MBC) assays. The biofilm Calgary device generated twenty-four hour biofilms to assess the anti-biofilm effect of XF-73 on biofilm viability through viable cell counts and through minimum biofilm inhibitory and eradication concentrations (MBIC/MBEC) assays. The antimicrobial activity of photo-activated XF-73 was also assessed following fifteen minutes blue light exposure at 420 nm (light dose = 13.8 J/cm2). XF-73 expressed a greater bactericidal activity against Gram-positive planktonic bacteria in comparison to Gram-negative microorganisms as MBCs ranged from ≤ 0.125 – 4 μg/ mL and 128 – >256 μg/ mL respectively. Photo-activation of XF-73 enhanced the bactericidal properties against both Gram-positive and Gram-negative bacteria as MBCs decreased to ≤ 0.03 – 1 μg/ mL and 32 – 128 μg/ mL. Gram-positive biofilms were highly susceptible to XF-73 with MBEC’s ranging from 1 – 2 μg/ mL. Photo-activation increased the bactericidal effect of XF-73 against Gram-positive biofilms with MBEC’s ranging between ≤ 0.125 – 0.5 μg/ mL. XF-73 was unable to eradicate Gram-negative biofilms, but concentrations 128 – 512 μg/ mL significantly reduced biofilm viability (p= <0.0001). XF-73 is a potent antimicrobial against Gram-positive microorganisms in both planktonic and biofilm modes of growth. Photo-activation further enhances the bactericidal effect of XF-73 and potentially offers an adjunct form of treatment in comparison to current antimicrobial treatment strategies. Further research is warranted in this area.

Date of Award	Sept 2022
Original language	English
Supervisor	Tony Worthington (Supervisor) & Jonathan A. G. Cox (Supervisor)