Antimicrobial photodynamic therapy alone or in combination with antibiotic local administration against biofilms of Fusobacterium nucleatum and Porphyromonas gingivalis

Abstract

Antimicrobial photodynamic therapy (aPDT) kills several planktonic pathogens. However, the susceptibility of biofilm-derived anaerobic bacteria to aPDT is poorly characterized. Here, we evaluated the effect of Photodithazine (PDZ)-mediated aPDT on Fusobacterium nucleatum and Porphyromonas gingivalis biofilms. In addition, aPDT was tested with metronidazole (MTZ) to explore the potential antimicrobial effect of the treatment. The minimum inhibitory concentration (MIC) of MTZ was defined for each bacterial species. Single-species biofilms of each species were grown on polystyrene plates under anaerobic conditions for five days. aPDT was performed by applying PDZ at concentrations of 50, 75 and 100 mg/L, followed by exposure to 50 J/cm LED light (660 nm) with or without MTZ. aPDT exhibited a significant reduction in bacterial viability at a PDZ concentration of 100 mg/L, with 1.12 log and 2.66 log reductions for F. nucleatum and P. gingivalis in biofilms, respectively. However, the antimicrobial effect against F. nucleatum was achieved only when aPDT was combined with MTZ at 100× MIC. Regarding P. gingivalis, the combination of PDZ-mediated aPDT at 100 mg/L with MTZ 100× MIC resulted in a 5 log reduction in the bacterial population. The potential antimicrobial effects of aPDT in combination with MTZ for both single pathogenic biofilms were confirmed by live/dead staining. These results suggest that localized antibiotic administration may be an adjuvant to aPDT to control F. nucleatum and P. gingivalis biofilms.

Antimicrobial Photodynamic Therapy: Latest Developments with a Focus on Combinatory Strategies

“…Target(s) In Vitro and/or In Vivo Effect(s) Reference 5-ALA + Gentamicin S. aureus and S. epidermidis In vitro: antibiofilm synergistic effect [392] Photodithazine + Metronidazole F. nucleatum and P. gingivalis In vitro: improvement of antibiofilm effect [393] Ce6 NP + Tinidazole Periodontal pathogenic bacteria In vitro: synergistic antiperiodontitis effects; in vivo: reduced adsorption of alveolar bone in a rat model of periodontitis [394] MB + Clindamycin/Amoxicillin E. coli In vitro: enhancement of antibiotic susceptibility following aPDT treatment; in vivo: prolonged survival of infected G. mellonella larvae [43] MB + Gentamicin S. aureus and P. aeruginosa…”

“…For instance, kanamycin, tobramycin, and gentamicin combined respectively to RB, porphyrin, and 5-Alanine have been reported, showing potent effects against bacteria of clinical interest, notably by improving biofilm clearance and reducing microbial loads [392,[430][431][432][433]. In addition, combinations with other antibiotic classes, such as nitroimidazoles (e.g., metronidazole) or glycopeptides (e.g., vancomycine), also showed some effect against biofilms of F. nucleatum and P. gingivalis [393], as well as S. aureus [434]. Further, PSs can also be useful to combine with antibiotics in order to restore the susceptibility of bacteria to the latter, notably to last-resort antibiotics.…”

In vitro antimicrobial effect of chloroaluminum phthalocyanine nanoemulsion on periodontal bacteria

“…[ 2 ] However, some studies suggest that this effect depends on system irradiation parameters, internalization, and subsequent activity of the PS. [ 4 ]…”

“…5-Diphenyltetrazolium bromide (Merck) and periodontopathogen bacteria (P gingivalis (ATCC 33277), A. actinomycetemcomitans (ATCC 33384), and P. intermedia (ATCC 25611) using the plate microdilution method according to Tavares et al ., 2018, respectively. [ 4 ] The nanoemulsion vehicle, ClAlPc (Sigma-Aldrich, St. Louis, MO, USA) dissolved in DMSO and 2% chlorhexidine gluconate from Ultra dent were evaluated as a reference. The light source used for PDT was a LED laser (660 nm), the cells were irradiated for 2 min using 4.83 joules/cm 2 .…”

Antibiotic Combination Therapy: A Strategy to Overcome Bacterial Resistance to Aminoglycoside Antibiotics

“…Some antibiotics combined with photosensitizer-mediated photodynamic antimicrobial chemotherapy (PACT) have been found to be with better antibacterial effects against bacteria ( Branco et al, 2018 ; Pérez-Laguna et al, 2018 ; Tavares et al, 2018 ). PACT mediated by photosensitizers will produce ROS under specific wavelength light stimulation, which induces phototoxic damage to bacteria ( Pérez-Laguna et al, 2019 ).…”