The Neisseria gonorrhoeae cytochrome c2-bacterial peroxidase electron-transfer complex is competent in hydrogen peroxide reduction
Year: 2025
Type: article
Abstract: Neisseria gonorrhoeae is a pathogenic bacterium responsible for the disease gonorrhea, which has gained increasing attention in recent years due to the emergence of strains resistant to the currently used antibiotics. In the absence of a vaccine, understanding mechanisms that contribute to infection is imperative. One such mechanism is the reduction of hydrogen peroxide by the outer membrane bound bacterial peroxidase. Here, steady-state kinetics shows that cytochrome c 2 , previously implicated in nitrite reduction, is an efficient electron donor to this enzyme, proving to be an alternative to the lipid-modified azurin. The cytochrome c 2 -mediated peroxidase activity has a K M of 0.74 ± 0.08 μM and a k obs of 18 ± 1 s −1 for hydrogen peroxide, with an optimum pH at 7.7. The pH and ionic-strength dependence of this activity differs from that of azurin, suggesting that the two electron donors can play complementary roles depending on external conditions. Furthermore, the viscosity dependence of the activity suggests that protein-protein interactions are not purely diffusion-controlled but also governed by conformational changes required for complex formation and/or electron transfer, and docking analysis indicates that cytochrome c 2 binding near the exposed edge of the electron transferring heme of the bacterial peroxidase. This study improves our understanding of the periplasmic physiology of N. gonorrhoeae by demonstrating how the pathogen's flexibility in using electron donors enables it to maintain peroxidase activity and cope with oxidative stress in different host environments. These insights could inform future strategies aimed at disrupting redox homeostasis to combat antibiotic-resistant strains. Synopsis Steady-state kinetics show that cytochrome c 2 is an efficient electron donor to bacterial peroxidase. This study improves our understanding of the periplasmic physiology of Neisseria gonorrhoeae by demonstrating how the pathogen's flexibility in using electron donors enables it to maintain peroxidase activity, coping with oxidative stress in different host environments. • Cytochrome c 2 is a competent electron donor to N. gonorrhoeae bacterial peroxidase. • pH-dependence of the mediated catalysis has a bell-shaped curve. • Viscosity-dependent activity suggests a non-purely diffusion-controlled interaction. • Cytochrome c 2 binds to the peroxidase near enzyme's electron transferring heme • Cytochrome c 2 -bacterial peroxidase complex has hydrophobic character
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,220
Awards: Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos, G2996174070, Unidade de Ciências Biomoleculares Aplicadas, Unidade de Ciências Biomoleculares Aplicadas, Destoxificação de peróxido de hidrogénio por Bactérias Patogénicas - Peroxidase tri-hémicas de E.coli como modelo, Instituto para a Saúde e a Bioeconomia, Novas peroxidases do citocromo c de bactérias patogénicas, Neisseria gonorrhoeae e Escherichia coli, Biochemical characterization of cytochrome c2 involved in NO formation and H2O2 detoxification in Neisseria gonorrhoeae”,, Biochemical and functional characterization of enzymes from Neisseria gonorrhoeae and Staphylococcus aureus involved in the infection process, Laboratório Associado para a Química Verde - Tecnologias e Processos Limpos
OpenAlex ID: W4416642983