FIG. 4.

Hypothetical mechanism of antimicrobial action of transferrins. (A) In L. lactis glucose-fermenting cells, H⁺ pumping through the ATPase (a) is essential for generation of a proton motive force across the cytoplasmic membrane (CM) and for intracellular pH homeostasis, and the latter is critical for cell survival. The blocking effect of lactoferrin (Lf) on H⁺-ATPase (b) causes an intracellular H⁺ accumulation, and then the acidification of the bacterial cytoplasm reaches levels incompatible with cell life. L. lactis cells lack a functional respiratory chain (NADHd type II, mQ, and cytochrome bd [Cyt bd]) under these experimental conditions. (B) Respiration of P. aeruginosa coupled to ATP synthase-mediated phosphorylation (a) is uncoupled by the blocking effect of lactoferrin (Lf) or transferrin (Tf) on the ATPase complex (b). Under these experimental conditions, the H⁺ accumulation in the periplasmic space (PS) leads to cell death. Cellular protection was observed when protons were not pumped to the PS (i.e., anaerobiosis or inhibition of NADHd type I with piericidin A). In anaerobiosis, the presence of the electron acceptor DCIP promotes the H⁺ pumping mediated by electron transport chain components (e.g., NADHd type I), yielding a lethal effect in Lf- or Tf-treated cells. In P. aeruginosa, electrons are donated from Cyt c to either Cyt cbb₃ I, Cyt cbb₃ II, or Cyt aa₃ (white). Cyt CIO and Cyt ba₃ (gray) directly accept electrons from CoQ (9). Relevant steps of anaerobic respiration are indicated (green arrows).