Lecture 13 1
CELL TO CELL SIGNALLING III
Additional AHL Functions (Kaufmann et al, Jan 2005 PNAS)
During a study to determine the lifespan of Pa. LasI AHL
in water, it was discovered that 3oxoC12 underwent an
unexpected reaction to a compound belonging to a class
of compounds called tetramic acids. (compound 4)
These compounds have potent antibacterial activity.
Structure resembles known antibacterials and antifungals.
A variety of AHLs were subjected to the same conditions
and all formed tetramic acids irrespective of chain length.
Significant antibacterial activity was found for compound 4
towards all tested Gram + bacteria, and none was found
towards any Gram – bacteria.
The activity is biologically relevant because AHL concentrations
are high and other antibacterials have similar activities. Lecture 13 2
Bacillus’ lactonase (Aii) activity protected from compound
1 (AHL), but not compound 4.
Maybe this activity is useful not only to disrupt QS, but
also to reduce toxicity.
Lactobacillus reutercyclin is
bactericidal as it acts as a
proton-ionophore (carries ions),
dissipating the transmembrane
change in pH and leading to cell
lysis (probably due to its high
Structural resemblance between
compound 4 and antibacterials
Interestingly, 3oxoC12 also
Not due to tetramic acid formed
since the experiment did not run
long enough for spontaneous
B. cereus strains
producing a penicillinase
were resistant to C12 AHL
and not to compound 4. Lecture 13 3
Because B. cereus produce lactonases, perhaps signaling
interference or “quorum quenching” is not the real goal of
Instead they may permit survival of cytotoxicity.
This would eliminate toxic effects of 1 and prevent
formation of 4.
And maybe 3 oxoC12 AHL evolved as signaling molecules
because of their fortuitous cytotoxic abilities, and their ability
to convert to tetramic acids, which are resistant to lactonase
Compound 4 also has the structure of a simple
siderophore, complexing 1 Fe for every 3 tetramic acids Lecture 13 4
The affinity constant for compound 4 is quite high, much
higher than one of Pa.’s normal siderophores, and similar
to other iron chelators.
Whether iron complexation i