Mechanisms of hop inhibition: hop ionophores.
In this work, the mechanism of hop inhibition toward (beer spoiling) bacteria is revised. The mode of action of iso-alpha-acids was investigated via bilayer lipid membrane (BLM) measurements and growth challenges of hop-sensitive and -resistant Lactobacillus brevis strains in the presence of uncouplers of class I and II or a H(+)/Mn(2+) exchanger. The antibacterial action of iso-alpha-acids as proton ionophores could be confirmed by the BLM measurements; however, the reported ionophore properties, as electroneutral H(+)/Mn(2+) exchangers, could not be verified. Potentiometric measurements indicated the manganese-dependent enhancement of transmembrane charge permeation. The origin of high membrane potentials in the presence of manganese, as well as the strongly elevated membrane conductivity with concomitant increase in effectiveness of an uncoupler, suggest a different origin of charge transfer under these conditions. The mode of antibacterial action of hop ionophores can be described as proton ionophores of class I/II, which are capable transporting protons within a wide range of pH due to their inherent complexity of chemical composition. However, growth challenges in the presence of both types of ionophore classes in combination with the measured unusual high BLM potentials in the presence of manganese and at low pH indicate an additional mechanism of inhibition by hop compounds. The latter may be due to the nature/properties of hop compounds, which are known to be highly reactive substances. As a consequence, hop resistance of bacteria can be described as multiple resistance to a heterogeneous mixture of compounds comprising different known and yet unknown charge transport mechanisms, which were dependent on several factors, for example, compound concentrations, cation composition, and pH value. Thus, only specialists such as some L. brevis strains, which can cope with unusually low intracellular manganese levels, can survive hop stress. Accordingly, cross-resistance to single proton ionophores or H(+)/Mn(2+) exchangers was not detectable and cannot be expected.
Behr
Jürgen
J
Technische Mikrobiologie, Technische Universitat Munchen, D-85350 Freising, Germany.
Vogel
Rudi F
RF
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001515:Beer / Q000382:microbiology*; D000001:Calcimycin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D027582:Humulus / Q000737:chemistry*; D007476:Ionophores / Q000494:pharmacology*; D052196:Levilactobacillus brevis / Q000187:drug effects*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008345:Manganese / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects
D000900:Anti-Bacterial Agents; D007476:Ionophores; D008051:Lipid Bilayers; D000001:Calcimycin; D008345:Manganese