Effect of nitric oxide on staphylococcal killing and interactive effect with superoxide

Abstract

The role of reactive nitrogen intermediates (RNI) such as nitric oxide ( . NO) in host defense against pyogenic microorganisms is unclear, and the actual interactive effect of RNI and reactive oxidative intermediates (ROI) for microbial killing has not been determined. Since, in nature, ROI and RNI might be generated together within any local infection, we evaluated the separate and interactive effects of . NO and O 2 ؊ on staphylococcal survival by using a simplified system devoid of eukaryotic cells. These studies showed that prolonged exposure of staphylococci to . NO does not result in early loss of viability but instead is associated with a dose-related delayed loss of viability. This effect is abrogated by the presence of hemoglobin, providing further evidence that the effect is RNI associated. Superoxide-mediated killing also is dose related, but in contrast to RNI-mediated killing, it is rapid and occurs within 2 h of exposure. We further show that the interaction of . NO and O 2 ؊ results in decreased O 2 ؊ -mediated staphylococcal killing at early time points. . NO, however, appears to enhance or stabilize microbial killing over prolonged periods of incubation. This study did not produce evidence of early synergism of ROI and RNI, but it does suggest that . NO may contribute to host defense, especially when ROI-mediated killing is compromised.

Oxidative and nitrosative stress in Staphylococcus aureus biofilm

“…They also provided evidence that nitrite-derived NO played a role in the inhibition of biofilm formation and that biofilm-embedded staphylococci could be efficiently killed by nitrite in an acidic environment. Despite NO exposure being able to reduce staphylococcal viability (Kaplan et al, 1996), S. aureus has been described as being relatively resistant to growth inhibition by NO, principally by the observation of efficient NO scavenging mechanisms, where flavohemoprotein Hmp was shown to play a crucial role in counteracting NO toxicity (Richardson et al, 2006). In this study, we observed that oxidative and nitrosative stress could be produced inside biofilms, thereby affecting their growth under different conditions and resulting in ROS and RNI production, with a decrease of the extracellular matrix.…”

Induction of NOS in rat blood PMN in vivo and in vitro: modulation by tyrosine kinase and involvement in bactericidal activity

“…In addition to this harmful effect of NO, it also has host protective effects. NO may play a role in neutrophilmediated tumor cytostasis [16] or may act as a backup antimicrobial system [13,14]. We have recently shown that NO can be an important candidacidal agent in rat PMN [15].…”

“…Concerning the role of NO produced by leukocytes, it has been extensively reported that this molecule participates in the killing activity against different pathogens [13,14]. We recently demonstrated that NO is involved in the candidacidal activity of rat inflammatory peritoneal neutrophils [15] and other authors have shown that NO contributes to the tumoricidal activity of those cells [16].…”

Nitric oxide and redox mechanisms in the immune response

“…Other bacterial pathogens such as Staphylococcus exhibit a different response to redox-mediated attack. The simultaneous presence of NO and peroxide in staphylococcal infections leads to a protective effect, where NO reduces ROS-mediated toxicity to the bacteria [60]. Yet, when Staphylococcus bacteria are exposed first to peroxide followed by NO, increased toxicity is observed [60].…”

“…The simultaneous presence of NO and peroxide in staphylococcal infections leads to a protective effect, where NO reduces ROS-mediated toxicity to the bacteria [60]. Yet, when Staphylococcus bacteria are exposed first to peroxide followed by NO, increased toxicity is observed [60]. In this case, it is the sequential exposure to a burst of superoxide/ROS production followed by NO that is critical for the maximum killing effect by these redox molecules.…”