Gdańsk Medical University

About: Gdańsk Medical University is a education organization based out in Gdańsk, Poland. It is known for research contribution in the topics: Population & Cancer. The organization has 4893 authors who have published 11216 publications receiving 260523 citations.

Superoxide dismutase is upregulated in Staphylococcus aureus following protoporphyrin-mediated photodynamic inactivation and does not directly influence the response to photodynamic treatment

Abstract: Background: Staphylococcus aureus, a major human pathogen causes a wide range of disease syndromes. The most dangerous are methicillin-resistant S. aureus (MRSA) strains, resistant not only to all b-lactam antibiotics but also to other antimicrobials. An alarming increase in antibiotic resistance spreading among pathogenic bacteria inclines to search for alternative therapeutic options, for which resistance can not be developed easily. Among others, photodynamic inactivation (PDI) of S. aureus is a promising option. Photodynamic inactivation is based on a concept that a non toxic chemical, called a photosensitizer upon excitation with light of an appropriate wavelength is activated. As a consequence singlet oxygen and other reactive oxygen species (e.g. superoxide anion) are produced, which are responsible for the cytotoxic effect towards bacterial cells. As strain-dependence in photodynamic inactivation of S. aureus was observed, determination of the molecular marker(s) underlying the mechanism of the bacterial response to PDI treatment would be of great clinical importance. We examined the role of superoxide dismutases (Sod) in photodynamic inactivation of S. aureus as enzymes responsible for oxidative stress resistance. Results: The effectiveness of photodynamic inactivation towards S. aureus and its Sod isogenic mutants deprived of either of the two superoxide dismutase activities, namely SodA or SodM or both of them showed similar results, regardless of the Sod status in TSB medium. On the contrary, in the CL medium (without Mn ++ ions) the double SodAM mutant was highly susceptible to photodynamic inactivation. Among 8 clinical isolates of S. aureus analyzed (4 MRSA and 4 MSSA), strains highly resistant and strains highly vulnerable to photodynamic inactivation were noticed. We observed that Sod activity as well as sodA and sodM transcript level increases after protoporphyrin IX-based photodynamic treatment but only in PDI-sensitive strains. Conclusions: We confirmed that porphyrin-based photokilling efficacy is a strain-dependent phenomenon. We showed that oxidative stress sensitivity caused by the lack of both Sod enzymes can be relieved in the presence of Mn ions and partially in the presence of Fe ions. The fact that Sod activity increase is observed only in PDIsusceptible cells emphasizes that this is probably not a direct factor affecting S. aureus vulnerability to porphyrinbased PDI.

Endothelial NADH/NADPH-dependent enzymatic sources of superoxide production: relationship to endothelial dysfunction

Abstract: There is growing evidence that endothelial dysfunction, which is often defined as the decreased endothelial-derived nitric oxide (NO) bioavailability, is a crucial factor leading to vascular disease states such as hypertension, diabetes, atherosclerosis, heart failure and cigarette smoking. This is due to the fact that the lack of NO in endothelium-dependent vascular disorders contributes to impaired vascular relaxation, platelet aggregation, increased vascular smooth muscle proliferation, and enhanced leukocyte adhesion to the endothelium. During the last several years, it has become clear that reduction of NO bioavailability in the endothelium-impaired function disorders is associated with an increase in endothelial production of superoxide (O(2)(*-)). Because O(2)(*-) rapidly scavenges NO within the endothelium, a reduction of bioactive NO might occur despite an increased NO generation. Among many enzymatic systems that are capable of producing O(2)(*-), NAD(P)H oxidase and uncoupled endothelial NO synthase (eNOS) apparently are the main sources of O(2)(*-) in the endothelial cells. It seems that O(2)(*-) generated by NAD(P)H oxidase may trigger eNOS uncoupling and contribute to the endothelial balance between NO and O(2)(*-). That is maintained at diverse levels.