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Robert C. Allen

Robert C. Allen

Creighton University School of Medicine

Title: Selective myeloperoxidase-bacteria binding and killing: Mechanism for establishing and maintaining lactic acid bacteria (LAB) as normal fl ora

Biography

Biography: Robert C. Allen

Abstract

Lactic acid bacteria (LAB) lack cytochrome synthesis and the electron transport mechanisms required for effi cient oxygenbased
metabolism. LAB redox activity is fl avoenzyme-based and metabolism is fermentative resulting in production of
lactic acid, and in many cases, hydrogen peroxide (H2O2). LAB occupy dominant positions within the normal fl ora of the
mouth, vagina and lower gastrointestinal tract in man. Neutrophil leukocytes and monocytes provide innate immune defense
against infecting pathogens. Th ese phagocytes synthesize relatively large quantities of myeloperoxidase (MPO), a unique
microbicidal haloperoxidase that catalyzes the H2O2-dependent oxidation of chloride (Cl-) to hypochlorite (OCl-); OCl- can
directly react with a second H2O2 producing singlet molecular oxygen (1O2*), a metastable electronically excited state of oxygen
with a microsecond half-life that restricts its potent electrophilic reactivity to within a radius of about 0.2 micron from its
generation. A healthy human adult generates about a hundred billion neutrophils per day. Infl ammation, infection and G-CSF
treatment greatly increase neutrophil production and the concentration of MPO/neutrophil. Aft er a short circulating lifetime,
neutrophils leave the blood and migrate into body spaces including the mouth, vagina, et cetera. Neutrophils lavaged from
the mouth of healthy humans are in proportion to the blood neutrophil count. MPO selectively binds to all Gram-negative
and many Gram-positive bacteria we have tested. However, MPO does not show signifi cant binding to LAB. Migration of
neutrophils to body spaces delivers MPO into a milieu conditioned by LAB fermentative action. Th e acid and H2O2 drive
extra-phagocyte MPO microbicidal action against MPO-bound microbes. Selectivity of MPO binding results in selective
killing, and provides a mechanism for establishing and maintaining LAB as the normal fl ora of man.