Agriculture Reference
In-Depth Information
AI-2 from
Vibrio harveyi
was chemically identified as a furanosyl borate diester [Chen
et
al.
, 2002], and it was later demonstrated that DPD spontaneously cyclizes and forms AI-2 in
the presence of borate [Semmelhack
et al.
, 2005]. However, other bacterial species produce
AI-2 after different rearrangements of the DPD moieties [Camilli and Bassler, 2006]. To date,
it is known that six compounds can arose from DPD. Therefore, all DPD-derived molecules
that show QS-activity are named collectively autoinducer-2 [Vendeville
et al.
, 2005].
In addition to the production of the DPD precursor, the LuxS enzyme has an important
metabolic function in the AMC, namely the recycling of the toxic metabolite
S
-
adenosylhomocysteine (SAH) to homocysteine (Figure 4) [Williams
et al.
, 2007]. As in the
case of AHLs, the amino acid precursor of AI-2 is
S
-adenosylmethionine (SAM), from which
DPD is generated through three enzymatic steps [Schauder and Bassler, 2001]. Consumption
of SAM as a methyl donor produces SAH, which is subsequently detoxified by the
nucleosidase Pfs to yield adenine and
S
-ribosylhomocysteine (SRH). SRH is then converted
to 4,5-dihydroxy-2,3-pentanedione (DPD) and homocysteine by LuxS. An alternative
pathway does exist, via
S
-adenosylhomocysteine hydrolase (SAHh) [Sun
et al.
, 2004].
In
Vibrio harveyi
, the LuxS-generated signals are detected and transduced by the
LuxP/LuxQ proteins. LuxP is a periplasmic binding protein which acts as receptor for AI-2,
forming a complex that subsequently interacts with the inner membrane-bound LuxQ sensor
histidine quinase, which transduces the AI-2 information into the cytoplasm and activates the
response through a rather complex mechanism, involving a phosphorelay system and small
regulatory RNAs [Vendeville
et al.
, 2005, Williams
et al.
, 2007]. However, the model of
detection-transduction of the AI-2 signal is rather different in
Salmonella typhimurium
,
Escherichia coli
and other species [Vendeville
et al.
, 2005].
The function of AI-2 as a QS signal molecule in bacteria other than
Vibrio
spp. has been
questioned, and this molecule has been suggested for most bacteria to be a metabolic side
product in the AMC pathway [Winzer
et al
., 2002, Chhabra
et a
l., 2005]. Analysis of 138
complete genomes revealed that even though the LuxS enzyme is widespread in bacteria, the
periplasmic binding protein LuxP is only present in
Vibrio
strains [Sun
et al.
, 2004]. The
open question is to elucidate whether other organisms use components different from the AI-2
signal transduction system of
Vibrio
strains to sense the signal of AI-2 (i.e. the
Salmonella
typhimurium
case), or if they actually lack AI-2 based QS. Many studies evidence important
implications of the AI-2 regulatory role in the expression of virulence factors by a number of
pathogenic bacteria. It has been shown that by using chemically synthesized AI-2 it is
possible to restore several phenotypes in
luxS
-
mutants of seven different genera of
pathogenic bacteria (
Clostridium perfringens
, enterohemorrhagic
Escherichia coli
,
Helycobacter pylori
,
Porphyromonas gingivalis
,
Shigella flexneri
,
Streptococcus mutans
and
Vibrio vulnificus
)
(for a review, see Vendeville
et al.
, 2005). Studies based on microarray
techniques revealed that AI-2 is involved in the regulation of over 400 genes in
Escherichia
coli
strains, and of more than 300 genes in
Photorhabdus luminescens
[González and
Keshavan, 2006, Krin
et al
., 2006].
The use of AI-2 as a QS signal by both Gram negative and Gram positive bacteria
suggest that is the earliest bacterial autoinducer and may have evolved before the divergence
between Gram negative and Gram positive bacteria [Schauder and Bassler, 2001].
Consolidation of the idea of AI-2 acting as a universal bacterial language and its role in
interspecies communication is an exciting challenge for future research on QS.
