In vitro photoinactivation of bovine mastitis related pathogens

Antimicrobial photodynamic inactivation (aPDI) uses photosensitizers (PSs) and harmless visible light to generate reactive oxygen species (ROS) and kill microbes. Multidrug efflux systems can moderate the phototoxic effects of PSs by expelling the compounds from cells. We hypothesized that increasing intracellular concentrations of PSs by inhibiting efflux with a covalently attached efflux pump inhibitor (EPI) would enhance bacterial cell phototoxicity and reduce exposure of neighboring host cells to damaging ROS. In this study, we tested the hypothesis by linking NorA EPIs to methylene blue (MB) and examining the photoantimicrobial activity of the EPI−MB hybrids against the human pathogen methicillin-resistant Staphylococcus aureus (MRSA). Photochemical/photophysical and in vitro microbiological evaluation of 16 hybrids carrying four different NorA EPIs attached to MB via four linker types identified INF55-(Ac)en−MB 12 as a lead. Compound 12 showed increased uptake into S. aureus cells and enhanced aPDI activity and wound healing effects (relative to MB) in a murine model of an abrasion wound infected by MRSA. The study supports a new approach for treating localized multidrug-resistant MRSA infections and paves the way for wider exploration of the EPI−PS hybrid strategy in aPDI.

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“…Preserving host tissues around infection sites should also provide benefits for wound healing through photo-biomodulation effects. 54,55 …”

Section: Discussionmentioning

confidence: 99%

Attaching the NorA Efflux Pump Inhibitor INF55 to Methylene Blue Enhances Antimicrobial Photodynamic Inactivation of Methicillin-Resistant Staphylococcus aureus in Vitro and in Vivo

Rineh

Dolla

Ball³

et al. 2017

ACS Infect. Dis.

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“…Treatment of this disease is based on the application intra-mammary antibiotic, which favors an increase in the number of resistant bacteria in the last decade. Sellera et al [208] investigated the efficacy of MB-aPDI in the inactivation of pathogens associated with bovine mastitis ( S. aureus, Streptococcus agalactiae, Streptococcus dysgalactiae, Corynebacterium bovis , and the alga Prototheca zopfii ). S. dysgalactiae, S. aureus , and C. bovis were inactivated after 30 s of irradiation, whereas S. agalactiae was inactivated after 120 s and P. zopfii at 180 s of irradiation.…”

Section: Apdi For Treating Localized Infectionsmentioning

confidence: 99%

Advances in antimicrobial photodynamic inactivation at the nanoscale

2017

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The alarming worldwide increase in antibiotic resistance amongst microbial pathogens necessitates a search for new antimicrobial techniques, which will not be affected by, or indeed cause resistance themselves. Light-mediated photoinactivation is one such technique that takes advantage of the whole spectrum of light to destroy a broad spectrum of pathogens. Many of these photoinactivation techniques rely on the participation of a diverse range of nanoparticles and nanostructures that have dimensions very similar to the wavelength of light. Photodynamic inactivation relies on the photochemical production of singlet oxygen from photosensitizing dyes (type II pathway) that can benefit remarkably from formulation in nanoparticle-based drug delivery vehicles. Fullerenes are a closed-cage carbon allotrope nanoparticle with a high absorption coefficient and triplet yield. Their photochemistry is highly dependent on microenvironment, and can be type II in organic solvents and type I (hydroxyl radicals) in a biological milieu. Titanium dioxide nanoparticles act as a large band-gap semiconductor that can carry out photo-induced electron transfer under ultraviolet A light and can also produce reactive oxygen species that kill microbial cells. We discuss some recent studies in which quite remarkable potentiation of microbial killing (up to six logs) can be obtained by the addition of simple inorganic salts such as the non-toxic sodium/potassium iodide, bromide, nitrite, and even the toxic sodium azide. Interesting mechanistic insights were obtained to explain this increased killing.

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“…A PDI experiment is performed by placing a PS in contact with a microorganism 1 (bacteria, virus, fungi protozoa, and pathogenic algae) [16,17], followed by local light 2 irradiation of the PS with the wavelength at the absorption maximum [18]. In addition to 3 the parameters associated with the light, such as its wavelength and fluence, and the PS 4 concentration, another important factor for PDI is the process of PS administration to the 5 microorganism.…”

Section: Conclusion: 27mentioning

confidence: 99%