Bioenergetic Mechanism for Nisin Resistance, Induced by the Acid Tolerance Response of Listeria monocytogenes

Abstract

ABSTRACT This study examined the bioenergetics of Listeria monocytogenes , induced to an acid tolerance response (ATR). Changes in bioenergetic parameters were consistent with the increased resistance of ATR-induced (ATR + ) cells to the antimicrobial peptide nisin. These changes may also explain the increased resistance of L. monocytogenes to other lethal factors. ATR + cells had lower transmembrane pH (ΔpH) and electric potential (Δψ) than the control (ATR − ) cells. The decreased proton motive force (PMF) of ATR + cells increased their resistance to nisin, the action of which is enhanced by energized membranes. Paradoxically, the intracellular ATP levels of the PMF-depleted ATR + cells were ∼7-fold higher than those in ATR − cells. This suggested a role for the F o F 1 ATPase enzyme complex, which converts the energy of ATP hydrolysis to PMF. Inhibition of the F o F 1 ATPase enzyme complex by N ′- N ′-1,3-dicyclohexylcarbodiimide increased ATP levels in ATR − but not in ATR + cells, where ATPase activity was already low. Spectrometric analyses (surface-enhanced laser desorption ionization-time of flight mass spectrometry) suggested that in ATR + listeriae, the downregulation of the proton-translocating c subunit of the F o F 1 ATPase was responsible for the decreased ATPase activity, thereby sparing vital ATP. These data suggest that regulation of F o F 1 ATPase plays an important role in the acid tolerance response of L. monocytogenes and in its induced resistance to nisin.