Role and regulation of the superoxide dismutases of Staphylococcus aureus

Karavolos, Michail H.; Horsburgh, Malcolm J.; Ingham, Eileen; Foster, Simon J.

doi:10.1099/mic.0.26353-0

Cited by 182 publications

(174 citation statements)

References 59 publications

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“…We can hypothesize that oxidative stress-associated toxicity is a result of cell wall and bacterial membrane damage, which leads to loss of cell viability. 48 In our study, we can speculate that apart from the singlet oxygen and the superoxide anion, other ROS may have been generated during the photosensitizer-mediated photodynamic processes, which could affect the SOD regulatory pathways.…”

Section: Discussionmentioning

confidence: 72%

Photodynamic Effects of Curcumin Against Cariogenic Pathogens

Araújo

Fontana

Bagnato

et al. 2012

Photomedicine and Laser Surgery

101

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Background data: The presence of Streptococcus mutans and Lactobacillus acidophilus in dental structure is an indicator of a cariogenic biofilm. Photodynamic therapy is a technique that involves the activation of photosensitizers by light in the presence of oxygen, resulting in the production of reactive radicals capable of inducing cell death. Reduction of bacteria levels can provide additional means of preventing dental caries. Objective: The present study evaluated the susceptibility of planktonic cultures of S. mutans (ATCC 25175) and L. acidophilus (ATCC-IAL-523) from the Adolfo Lutz Institute (IAL) to photodynamic therapy after sensitization with curcumin and exposure to blue light at 450 nm. Methods: Bacterial suspensions of S. mutans and L. acidophilus isolated (as single species) and combined (multspecies) were prepared and then evaluated. Four different groups were analyzed: L-D-(control group), L-D + (drug group), L + D-(light group), and L + D + (photodynamic therapy group). Two different concentrations of curcumin were tested (0.75 and 1.5 g/L) associated with a 5.7 J/cm 2 light emission diode. Results: Significant decreases ( p < 0.05) in the viability of S. mutans were only observed when the bacterial suspensions were exposed to both curcumin and light. Then, reductions in viability of up to 99.99% were observed when using 1.5 g/L of the photosensitizer. The susceptibility of L. acidophilus was considerably lower (21% and 37.6%) for both curcumin concentrations. Conclusions: Photodynamic therapy was found to be effective in reducing S. mutans and L. acidophilus on planktonic cultures. No significant reduction was found for L-D + , proving the absence of dark toxicity of the drug.

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Section: Discussionmentioning

confidence: 72%

Photodynamic Effects of Curcumin Against Cariogenic Pathogens

Araújo

Fontana

Bagnato

et al. 2012

Photomedicine and Laser Surgery

101

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“…To test this hypothesis, the ability of ΔS1 and ΔS2 CP to increase S. aureus sensitivity to superoxide, elevate intracellular superoxide levels, and reduce SOD activity was assessed. As an initial test, S. aureus was treated with WT CP, ΔS1, or ΔS2 and assessed for sensitivity to the superoxide-generating compound paraquat whose toxicity is greatly increased in SOD-deficient strains (13,24,25). WT CP and the ΔS2 mutant increased the sensitivity of S. aureus to paraquat whereas ΔS1 did not (Fig.…”

Section: Inhibition Of S Aureus Superoxide Defenses Requires Sequestmentioning

confidence: 99%

Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens

Damo

Kehl-Fie

Sugitani

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

340

594

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The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn 2+ and Zn 2+ with high affinity and starves bacteria of these essential nutrients. Combining biophysical, structural, and microbiological analysis, we identified the molecular basis of Mn 2+ sequestration. The asymmetry of the CP heterodimer creates a single Mn 2+ -binding site from six histidine residues, which distinguishes CP from all other Mn 2+ -binding proteins. Analysis of CP mutants with altered metal-binding properties revealed that, despite both Mn 2+ and Zn 2+ being essential metals, maximal growth inhibition of multiple bacterial pathogens requires Mn 2+ sequestration. These data establish the importance of Mn 2+ sequestration in defense against infection, explain the broad-spectrum antimicrobial activity of CP relative to other S100 proteins, and clarify the impact of metal depletion on the innate immune response to infection.bacterial pathogenesis | Staphylococcus aureus | antibiotic resistance | protein crystal structure | isothermal titration calorimetry B acterial pathogens are a significant threat to global public health. This threat is compounded by the fact that these organisms are rapidly becoming resistant to all relevant antimicrobials. Of particular note is the recent emergence of antibiotic-resistant strains of Staphylococcus aureus as a leading cause of bacterial infection in the United States (1) and arguably the most important threat to the public health of the developed world. Consequently, the identification of therapeutics to treat bacterial pathogens is paramount to our continued ability to limit this infectious threat.One promising area of potential therapeutic development involves targeting bacterial access to essential transition metals. This strategy is based on the fact that all bacterial pathogens require these nutrient metals to colonize their hosts (2-5). In vertebrates, the bacterial need for nutrient transition metals is counteracted by the sequestration of these metals by the host. This limitation of essential nutrients, termed "nutritional immunity," is a potent defense against infection (6). Although a variety of metals is required for microbial growth, studies of nutritional immunity have been primarily restricted to the struggle for iron (Fe) between host and pathogen (7-9).An innate immune factor, calprotectin (CP), is abundant in neutrophils and plays a key role in nutritional immunity. CP can be found at sites of infection in excess of 1 mg/mL and is required for the control of a number of medically relevant bacteria and fungi including S. aureus, Candida albicans, and Aspergillus fumigates (10-14). The antimicrobial activity of CP is due to the chelation of the essential nutrients Zn 2+ (Zn) and Mn 2+ (Mn), which results in bacterial metal starvation and is reversed by the addition of these metals in excess (11, 13). Moreover, CP-deficient mice have increased microbial burdens following systemic challenge, und...

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“…Paraquat is a generator of internal superoxide, which is converted by superoxide dismutase (SOD) enzymes to H 2 O 2 (26). In S. aureus, inactivation of the major SOD enzyme, encoded by sodA, results in reduced ability to survive paraquat stress (Fig.…”

Section: Inactivation Of Ahpcmentioning

confidence: 99%

“…In S. aureus, inactivation of the major SOD enzyme, encoded by sodA, results in reduced ability to survive paraquat stress (Fig. 3C) (26). The sensitivities of KC041 (ahpC), KS100 (katA), and KC043 (ahpC katA) to paraquat were tested using disk diffusion assays and compared to SH1000 (wild type) (Fig.…”

Section: Inactivation Of Ahpcmentioning

confidence: 99%

Catalase (KatA) and Alkyl Hydroperoxide Reductase (AhpC) Have Compensatory Roles in Peroxide Stress Resistance and Are Required for Survival, Persistence, and Nasal Colonization inStaphylococcus aureus

et al. 2007

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Oxidative-stress resistance in Staphylococcus aureus is linked to metal ion homeostasis via several interacting regulators. In particular, PerR controls the expression of a regulon of genes, many of which encode antioxidants. Two PerR regulon members, ahpC (alkylhydroperoxide reductase) and katA (catalase), show compensatory regulation, with independent and linked functions. An ahpC mutation leads to increased H 2 O 2 resistance due to greater katA expression via relief of PerR repression. Moreover, AhpC provides residual catalase activity present in a katA mutant. Mutation of both katA and ahpC leads to a severe growth defect under aerobic conditions in defined media (attributable to lack of catalase activity). This results in the inability to scavenge exogenous or endogenously produced H 2 O 2 , resulting in accumulation of H 2 O 2 in the medium. This leads to DNA damage, the likely cause of the growth defect. Surprisingly, the katA ahpC mutant is not attenuated in two independent models of infection, which implies reduced oxygen availability during infection. In contrast, both AhpC and KatA are required for environmental persistence (desiccation) and nasal colonization. Thus, oxidative-stress resistance is an important factor in the ability of S. aureus to persist in the hospital environment and so contribute to the spread of human disease.

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Role and regulation of the superoxide dismutases of Staphylococcus aureus

Cited by 182 publications

References 59 publications

Photodynamic Effects of Curcumin Against Cariogenic Pathogens

Photodynamic Effects of Curcumin Against Cariogenic Pathogens

Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens

Catalase (KatA) and Alkyl Hydroperoxide Reductase (AhpC) Have Compensatory Roles in Peroxide Stress Resistance and Are Required for Survival, Persistence, and Nasal Colonization inStaphylococcus aureus

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