Abstract
BackgroundStaphylococcus 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 β-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.ResultsThe 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.ConclusionsWe 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 PDI-susceptible cells emphasizes that this is probably not a direct factor affecting S. aureus vulnerability to porphyrin-based PDI.
Highlights
Staphylococcus aureus, a major human pathogen causes a wide range of disease syndromes
photodynamic inactivation (PDI) effectiveness towards wild type Staphylococcus aureus and its sod isogenic mutants With the use of type I or type II oxidative stress quenching agents, we checked that protoporphyrin IX (PpIX)-mediated PDI is involved in the type I mechanism of oxidative stress induction
In order to check superoxide dismutases’ role in photodynamic inactivation we first of all checked whether S. aureus RN6390 strain deprived of either SodA, SodM or both of the activities differentially responded to photodynamic inactivation
Summary
Staphylococcus aureus, a major human pathogen causes a wide range of disease syndromes. 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. We examined the role of superoxide dismutases (Sod) in photodynamic inactivation of S. aureus as enzymes responsible for oxidative stress resistance. Staphylococcus aureus, a major human pathogen causes a wide range of disease syndromes, including life-threatening endocarditis, meningitidis and pneumonia. S. aureus produces enzymes responsible for resistance against oxidative stress, like catalase and superoxide dismutase (Sod). Superoxide anion, which is the product of oxygen reduction, reacts with hydrogen peroxide within the bacterial cell and produces free hydroxyl radical (.OH), the most dangerous oxygen species able to interact with virtually any organic substance in the cell. Superoxide anion can reduce hypochlorus acid (HOCl) arose as a result of H2O2 interaction with phagocyte-derived peroxidases, and further form .OH [3]
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