Antimicrobial photodynamic therapy (aPDT) with curcumin controls intradermal infection by Staphylococcus aureus in mice with type 1 diabetes mellitus: a pilot study.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main pathogens that cause infections in diabetic individuals. In this paper, we report the outcomes of our investigation on the intradermal application of antimicrobial photodynamic therapy (PDT) with curcumin in an infection induced by MRSA ATCC 43300 strain in the ear of mice with Type 1 Diabetes Mellitus (T1DM). A solution containing 100 µg of curcumin was photoactivated ex vivo with a LED light (450 nm) delivering a fluency of 13.5 J/cm3. This solution was administered in the ear intradermally, at the same inoculum site as the MRSA ATCC 43300 strain (PDT Group). This study also included the use of two control groups (both infected): One was treated with saline and the other was treated with non-photoactivated curcumin. The animals were euthanized 24 h after these treatments and samples of draining lymph node and treated ear were collected for examination. The PDT group showed lower bacterial load in the draining lymph node when compared to the saline and curcumin groups (p-value <0.05) 24 h after treatment. In addition to bacterial load, the PDT group presented a higher concentration of nitrates and nitrites in the draining lymph node when compared to the saline and curcumin groups (p-value <0.001). Examining the infectious site, despite apparently having similar inflammatory cell recruitment compared with the control groups, the PDT group showed a profile with less intense activity in the myeloperoxidase expression when compared to the saline group (p-value <0.001). Additionally, the detected concentration of cytokines such as IL-1ß, IL-12, and IL-10 was significantly lower in the PDT group when compared to the saline group (p-value <0.01; p-value <0.05; p-value <0.05, respectively), thus presenting a less intense inflammatory response during infection resolution. Our pilot study showed for the first time the therapeutic potential of PDT using curcumin when administered intradermally in the treatment of infections caused by S. aureus in mice with T1DM.

Photoactivated resveratrol controls intradermal infection by Staphylococcus aureus in mice: a pilot study.

Staphylococcus aureus is one of the main causative agent of infections acquired in both community and hospital environment. In this context, photodynamic therapy (PDT) consists in using a photosensitizer that, activated by light, evokes the formation of reactive oxygen species (ROS), which lead to the death of microorganisms due to oxidative damage; it is useful tool since this action, harmful to pathogens, does not significantly injure human cells. In view of this, this work proposes a more in-depth study on the use of resveratrol (RSV) as a possible photosensitizer. It was observed, in the intradermal infection model in animals' ear dermis, that photoactivated resveratrol promotes an increase in myeloperoxidase expression with reduced bacterial load in the draining lymph node. Besides that, the draining lymph node of the animals treated with photoactivated RSV controls inflammation through IL-10 production. These are pioneers data and this work being a pilot study; then, other works must be conducted with the objective of elucidate the photoactivated resveratrol mechanism of action.

Efficacy of photoactivated Myrciaria cauliflora extract against Staphylococcus aureus infection - A pilot study.

Staphylococcus aureus is one of the major microorganisms that cause human diseases, leading from mild skin infections to serious diseases. With the use of semi-synthetic penicillins, methicillin-resistant strains called Methicillin-resistant Staphylococcus aureus (MRSA) have emerged, whose resistance pattern extends to other beta-lactam antibiotics. It has already been shown that photodynamic therapy is capable of inactivating MRSA as the laser excites the photosensitizer responsible for transferring its electrons to the molecular oxygen, generating extremely reactive molecules, such as singlet oxygen, being these reactive components the chemicals that promote the bacterial clearance. Thus, the research aiming at the development of new photosensitizers becomes important, especially to increase the amount of therapeutic resources available for the treatment of persistent infections related to this bacterium. In this context, Myrciaria cauliflora is a plant that has antimicrobial action and there are no reports of the use of its crude extract as a photosensitizer in antimicrobial photodynamic therapy. In that way, this work conveys an innovative way of the use of M. cauliflora extract as a photosensitizer, comprising its use as an antimicrobial agent when activated by light, against S. aureus. In vitro tests were performed where it was observed that after the photoactivation with blue LED light, the extract presented an augment in its antimicrobial activity, together with production of singlet oxygen. In the model of intradermal infection in Balb/c mice, a reduction in bacterial load was also detected, with raised expression of TNF-α, IL-17A, and MPO. Here, we demonstrate that the extract of M. cauliflora has photosensitizing action, promoting the production of singlet oxygen, besides IL-17A, TNF-α, and MPO.

Photoactivated resveratrol against Staphylococcus aureus infection in mice.

BACKGROUND: Among the pathogens, Staphylococcus aureus is the main causative agent of bacterial diseases in the world. In this context, antimicrobial photodynamic therapy (aPDT) appears as a promising tool by means of microbial inactivation with the use of light. aPDT is applied in treatments involving photosensitizers capable of generating oxygen free radicals. Thus, this work proposes the use of resveratrol as a photosensitizer. METHODS: In vitro tests were performed to determine the antibacterial activity of photoactivated resveratrol with blue LED light, as well as uric acid experiments for verification of singlet oxygen formation. Possible resveratrol structural changes were evaluated by HPLC. In the in vivo assays, the air pouch model was performed in mice for antimicrobial activity and cytokine production. RESULTS: The photoactivated resveratrol exhibited an increase in its antibacterial action and it is possibly brought about by the singlet oxygen formation. In the air pouch model, TNF-α and IL-17A cytokines were produced, diminishing the bacterial load, and consequently, reducing inflammation after 24 h of infection. Cellular number decrease in the inflammatory environment was associated with resolution of inflammation along with greater IL-10 production. CONCLUSION: It is the first time that resveratrol has been associated with aPDT. It was demonstrated in this work that resveratrol activated by blue LED light can be a promising photosensitizer. This compound, after the light stimulus, produces singlet oxygen, in addition to having effects on the immune system triggering TNF-α and IL-17A production, aiding in the clearance of several bacteria, including S. aureus.