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Increased virulence of Neisseria meningitidis after in vitro iron-limited growth at low pH

D Brener, I W DeVoe, B E Holbein

    Infection and Immunity
    |July 1, 1981
    PubMed

    Insights

    Low pH and iron limitation increase Neisseria meningitidis virulence by altering outer membrane proteins. This study highlights environmental factors influencing bacterial pathogenicity.

    Area of Science:

    • Microbiology
    • Pathogenesis
    • Bacterial Virulence Factors

    Background:

    • Neisseria meningitidis is a significant human pathogen.
    • Environmental factors like pH and nutrient availability can influence bacterial virulence.
    • Outer membrane proteins play a crucial role in bacterial-host interactions.

    Purpose of the Study:

    • To investigate the impact of low pH and iron limitation on Neisseria meningitidis group B (strain SD1C) outer membrane protein expression and virulence.
    • To characterize the specific outer membrane proteins affected by these environmental conditions.
    • To quantify the change in virulence associated with altered growth conditions.

    Main Methods:

    • Culturing N. meningitidis under varying pH (6.6, 7.2, 7.7) and iron availability (limited vs. sufficient).
    • Analyzing outer membrane protein profiles using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
    • Labeling surface-exposed proteins with [125I]lactoperoxidase and identifying them via autoradiography.
    • Determining relative virulence using the 50% lethal dose (LD50) in C57/BL mice.

    Main Results:

    • Low pH (6.6) and iron limitation induced an atypical outer membrane protein profile.
    • A major outer membrane protein (protein III, 69,000 MW) was significantly upregulated under low pH and iron-limited conditions.
    • Iron-limited cells grown at low pH exhibited a 1,200-fold increase in relative virulence (LD50 = 4.0 CFU) compared to iron-sufficient cells at neutral pH.

    Conclusions:

    • pH and iron availability are critical determinants of Neisseria meningitidis virulence.
    • Alterations in outer membrane protein expression, particularly protein III, are associated with increased pathogenicity under specific environmental conditions.
    • These findings have implications for understanding meningococcal disease pathogenesis and potential therapeutic strategies.

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