Work

Metabolic adaptation to host acetate facilitates oxidative stress resistance and intracellular survival of Neisseria meningitidis in macrophages

Year: 2025

Type: article

Abstract: Neisseria meningitidis encounters a dynamic nutrient landscape during host colonization, which necessitates its metabolic adaptation to different host metabolites such as acetate. Acetate, a short chain fatty acid (SCFA) within the host milieu, found to regulate host defense and inflammation during bacterial infection. In macrophage acetate gets converted into acetyl-CoA to provide energy via TCA cycle. Also, acetate is a crucial metabolic intermediate that takes part in lipid biosynthesis and protein acetylation. Acetate acts as an immunomodulator which improves the bactericidal effect of macrophage by activating the inflammasome. Therefore, to persist in nutrient limited conditions encountered in macrophages pathogens should resort to effective utilization of energy sources. We demonstrate that N. meningitidis can potentially utilize host acetate as a carbon source and regulate its virulence. The utilization of acetate enhanced the survival of N. meningitidis in H2O2 induced oxidative stress which can be correlated with the macrophage infection assay. Moreover, our investigation into underlying mechanism suggests that acetate exposure upregulates bacterial oxidative stress response by significantly increasing catalase and superoxide dismutase activity. We demonstrated that acetate metabolism also upregulated expression of nitric oxide detoxification genes fnr, narQ which mitigate reactive oxygen and nitrogen species produced in macrophages. Therefore, we conclude that bacterial utilization of physiologically relevant host acetate levels represents an important strategy to consume or detoxify macrophage-mediated oxidative stress, thereby facilitating bacterial survival.

Source: Virulence

DOI: 10.1080/21505594.2025.2566242

Authors: Tiyasa Haldar, Divya Tripathi, Sunil D. Saroj

Institution: Symbiosis International University

Language: English

Topic: Bacterial Infections and Vaccines

Subfield: Microbiology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,557