Biology Reference
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consistent with an effect on the bulk mem-
brane rather than a direct interaction of the
specific target protein, and the alkanols'
non-specificity of antimicrobial activity
supports this assumption. The possibility of
anti-
Salmonella
activity of the medium-
chain alkanols is due to their non-ionic sur-
factant property, but this may not be the
case for short-chain alkanols. The short-
chain alkanols enter the cell by passive dif-
fusion across the plasma membrane and/or
through porin channels (Schulz, 1996). On
the other hand, the more lipophilic long-
chain alkanol molecules, being dissolved
in the medium, are incorporated in part into
the lipid bilayers (Franks and Lieb, 1986).
The amount of alkanols entering into the
cytosol or lipid bilayer is dependent on the
length of the alkyl chain. None the less,
alkanols are chemically stable compounds
and may not react with any biologically
important substances in the cytosol or lipid
bilayer. Hence, the primary antibacterial
action of medium-chain alkanols comes
from their ability to function as non-ionic
surfactants (physical disruption of the mem-
brane). This may reveal the different effects
of alkanols on
S. choleraesuis
as compared
to the corresponding 2
E
-alkenals; that is,
a,b-unsaturated aldehydes are chemically
highly reactive substances and hence
2
E
-alkenals, being entered into the cytosol
or lipid bilayer, may readily react with bio-
logically important nucleophilic groups,
such as sulfhydryl, amino or hydroxyl
groups (Schauenstein
et al
., 1977). For
example, hexanol did not exhibit any activ-
ity against
S. choleraesuis
up to 1600 mg/ml,
whereas 2
E
-hexenal showed the bacteri-
cidal activity with a MBC of 100 mg/ml
(Kubo and Kubo, 1995; Bisignano
et al
.,
2001; Kubo and Fujita, 2001). It appears that
medium-chain 2
E
-alkenals first act as sur-
factants and are then involved in biochemi-
cal processes.
The same series of alkanols were
recently found to inhibit the succinate-
supported respiration of intact mitochon-
dria isolated from rat liver. The potency
increased with increasing chain length up
to undecanol. Given each alkanol's nearly
identical effect on State 3 and uncoupled
respiration, this action is not directly on the
ATP synthetase but earlier in the respiratory
process. Hexanol and decanol were assayed
against freeze-thawed (broken) mitochon-
dria to distinguish effects on the mitochon-
drial substrate carrier from that on the
electron transport chain. Both alcohols were
only weak inhibitors of respiration in bro-
ken mitochondria, suggesting that inhibi-
tion originates from interference with the
dicarboxylate carrier that must transport
succinate across the mitochondrial mem-
branes. Alkanols may inhibit this trans-
porter in the inner membrane as non-ionic
surfactants. The results with mitochondria
also support the alkanols' non-ionic sur-
factant concept because enzyme systems
related to transport of solutes and electron
transfer are located in the inner membrane
of the cell envelope of
Salmonella
(Hammond and Kubo, 2000). On the other
hand, alkanols with longer carbon-chain
length were previously reported to exert a
stronger inhibitory effect on the (Na
+
+K
+
)-
ATPase activity of the neural membranes
(Sun and Samorajski, 1975), probably by a
similar surfactant concept to that described
for H
+
-ATPase (Nikaido, 1994). Overall, it
seems that the anti-
Salmonella
activity of
alkanols is mediated by biophysical pro-
cesses. In addition, an increase in the alkyl
chain length results in a parallel increase in
the surface tension (Leshem
et al
., 1988).
Surface tension changes may be triggered in
another purely biophysical manner, which
needs to be considered. For example, sur-
face tension could affect mobility and/or
exposure of membrane-embedded proteins
such as enzymes and receptors. The data
obtained indicate, however, that the effect
of surface tension is not primarily related to
the activity (Bisignano
et al
., 2001) but can-
not be entirely ruled out.
In addition, the antibacterial activity of
the homologous series of alkanals against
S. choleraesuis
was also tested for compari-
son. The results are listed in Table 16.2.
Notably, the potency of the activity against
this foodborne bacterium was not increased
for each additional CH
2
group. Similar to
what is found for alkanols, the short-chain
alkenals enter the cell by passive diffusion
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