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Journal of Bacteriology, May 2000, p. 2702-2708, Vol. 182, No. 10
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
The Pseudomonas Quinolone Signal
Regulates rhl Quorum Sensing in Pseudomonas
aeruginosa
Susan L.
McKnight,1
Barbara H.
Iglewski,2 and
Everett
C.
Pesci1,*
Department of Microbiology and Immunology,
East Carolina University School of Medicine, Greenville, North
Carolina 27858,1 and Department of
Microbiology and Immunology, University of Rochester School of
Medicine, Rochester, New York 146422
Received 30 September 1999/Accepted 17 February 2000
 |
ABSTRACT |
The opportunistic pathogen Pseudomonas aeruginosa uses
intercellular signals to control the density-dependent expression of many virulence factors. The las and rhl
quorum-sensing systems function, respectively, through the autoinducers
N-(3-oxododecanoyl)-L-homoserine lactone and
N-butyryl-L-homoserine lactone
(C4-HSL), which are known to positively regulate the
transcription of the elastase-encoding gene, lasB.
Recently, we reported that a second type of intercellular signal is
involved in lasB induction. This signal was identified as
2-heptyl-3-hydroxy-4-quinolone and designated the
Pseudomonas quinolone signal (PQS). PQS was determined to
be part of the quorum-sensing hierarchy since its production and
bioactivity depended on the las and rhl
quorum-sensing systems, respectively. In order to define the role of
PQS in the P. aeruginosa quorum-sensing cascade, lacZ gene fusions were used to determine the effect of PQS
on the transcription of the quorum-sensing system genes
lasR, lasI, rhlR, and
rhlI. We found that in P. aeruginosa, PQS
caused a major induction of rhlI'-lacZ and had lesser
effects on the transcription of lasR'-lacZ and
rhlR'-lacZ. We also observed that the transcription of both
rhlI'-lacZ and lasB'-lacZ was cooperatively
effected by C4-HSL and PQS. Additionally, we present data
indicating that PQS was not produced maximally until cultures reached
the late stationary phase of growth. Taken together, our results imply that PQS acts as a link between the las and rhl
quorum-sensing systems and that this signal is not involved in sensing
cell density.
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INTRODUCTION |
Pseudomonas aeruginosa is
a ubiquitous environmental organism capable of infecting a wide variety
of animals, plants, and insects. As a human pathogen, this bacterium is
a major source of opportunistic infections in both immunocompromised
individuals and cystic fibrosis patients. P. aeruginosa is
now the leading source of gram-negative nosocomial infections
(25) and causes chronic lung infections in approximately
90% of cystic fibrosis patients (7). The ability of this
organism to cause devastating infections stems from the production of
an arsenal of virulence factors, several of which are controlled
according to cell density through an elegant mechanism known as quorum
sensing. In gram-negative bacteria, most quorum-sensing systems consist
of a LuxR-type transcriptional activator (R protein) and an acylated
homoserine lactone signal molecule (autoinducer) (see reference
4 for a review). When a bacterial culture is at a
low cell density, basal levels of autoinducer and R protein are
produced. As a population grows, the concentration of autoinducer
increases with cell density until it reaches a threshold concentration
where it binds to and thereby activates an R protein. Activated R
protein then activates specific genes, causing cell density-dependent
gene expression.
In P. aeruginosa, there are at least two quorum-sensing
systems, las and rhl, which control the
expression of numerous genes (see reference 21 for a
review). The las quorum-sensing system consists of the
transcriptional activator LasR and the autoinducer N-(3-oxododecanoyl)-L-homoserine lactone
(3-oxo-C12-HSL), the synthesis of which is directed by the
LasI autoinducer synthase (5, 15, 16). Similarly, the
rhl system consists of the transcriptional activator RhlR
and the autoinducer N-butyryl-L-homoserine lactone (C4-HSL), the synthesis of which is directed by the
RhlI autoinducer synthase (12, 13, 17). Together, the
las and rhl systems have been shown to regulate
between 1 and 4% of the genes carried by P. aeruginosa,
demonstrating the global importance of these intercellular signaling
systems (27).
While the las and rhl quorum-sensing systems
consist of two separate regulons, their functions are apparently not
independent. Both of these systems have been shown to control the
transcription of lasB, which encodes the major virulence
factor LasB elastase (2, 5, 8, 18). It has also been shown
that the las quorum-sensing system controls the
rhl quorum-sensing system at both the transcriptional and
posttranslational levels (9, 20). The discovery of this link
between the systems indicated that they were arranged in a hierarchy
where the las quorum-sensing system is dominant over the
rhl quorum-sensing system.
Recently, we reported that P. aeruginosa produced a third
intercellular signal in addition to the two homoserine lactone-type autoinducers. The Pseudomonas quinolone signal (PQS), which
is capable of inducing lasB in P. aeruginosa, was
identified as 2-heptyl-3-hydroxy-4-quinolone (22). Our
initial characterization of PQS indicated that the production of this
novel intercellular signal occurred only in the presence of an active
form of LasR. We also demonstrated that exogenous PQS exhibited
bioactivity in the lasR mutant strain PAO-R1 but not in the
lasR rhlR double mutant strain PAO-JP3. Taken together,
these results suggested that LasR was required for PQS production and
that RhlR was important for PQS bioactivity (22). This
indicated that PQS was intertwined in the quorum-sensing hierarchy, but
because of the induction cascade that occurs, its exact role was
difficult to determine. Therefore, we set out to further characterize
PQS bioactivity and production.
In this report, we present data indicating that PQS provides a link
between the las and rhl quorum-sensing systems.
We show that PQS strongly induced rhlI in P. aeruginosa and had lesser positive effects on the transcription of
lasR and rhlR. Our data indicated that
rhlI and lasB are both cooperatively regulated by
PQS and C4-HSL. We also determined that PQS was produced
maximally in late stationary phase, suggesting that this intercellular
signal was not involved in sensing cell density. These exciting results imply an expanded role for P. aeruginosa cell-to-cell
signaling and suggest a revised model of P. aeruginosa
quorum sensing.
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MATERIALS AND METHODS |
Bacterial strains, plasmids, and culture conditions.
The
bacterial strains and plasmids utilized in this study are listed in
Table 1. For each experiment, strains
were plated from 10% milk stocks maintained at 
70°C. All P. aeruginosa strains were grown in PTSB (5% peptone, 0.25% tryptic
soy broth, pH 7.0) (14) supplemented with 200 µg of
carbenicillin per ml when appropriate. All cultures were grown at
37°C, and liquid cultures were shaken at 270 rpm. Plasmids were
transformed into P. aeruginosa by electroporation (24).
PQS bioassays.
PQS bioassays were performed as described
previously (22). Briefly, cells from overnight cultures were
harvested by centrifugation and resuspended in PTSB. These washed cells
were used to inoculate fresh medium to a starting
A660 of 0.05. At mid-log phase, subcultures were
adjusted (using washed cells) to an A660 of 0.02 in fresh medium and added to tubes containing dried signal molecules or extracts. Synthetic PQS was used in all bioassays except those performed with the extracts from the growth curve experiments. The
cultures were grown for 18 h and assayed in duplicate for 
-galactosidase (-Gal) activity as described by Miller
(10).
Growth curve extracts.
Freshly plated cells of P. aeruginosa strain PAO-JP2(pECP39) were inoculated into 10 ml of
medium and grown overnight. Subcultures were started at an
A660 of 0.05 and grown until they reached the log phase of growth. At that time, the cells were washed with PTSB and
used to adjust 400 ml of medium to an A660 of
0.05. At specified time points over the next 48 h, a 10-ml aliquot
was removed for A660 determinations and ethyl
acetate extractions. Aliquots were centrifuged at 10,000 × g for 10 min at room temperature, and the supernatant was
extracted twice with equal volumes of ethyl acetate (22).
Water was removed from the extracts by the addition of sodium sulfate
followed by evaporation of the solvent in a rotary evaporator. The
dried extracts were stored at 20°C until being assayed for PQS
activity as described previously, using the bioassay strain P. aeruginosa PAO-R1(pTS400) (22). This experiment was
repeated four times, and results are presented as the percentage of the
maximal activation seen during each separate experiment.
Viability growth curves.
Washed cells from late-log-phase
cultures of P. aeruginosa strains PAO-JP2(pECP39) and PAO1
were used to start a 35-ml subculture at an A660
of 0.05. At specified intervals, 1 ml of each culture was removed and
the A660 was determined. Serial dilutions were spread on duplicate plates which were incubated overnight at 37°C. Colonies on plates with between 30 and 300 colonies were counted, and
these data were used to produce viability curves. Viability curves were
repeated at least twice, and results are presented as the mean
CFU/ml ± 
n 
1.
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RESULTS |
PQS induces rhlI in P. aeruginosa.
Previous research has shown that PQS was capable of inducing
lasB expression in P. aeruginosa
(22). During the initial characterization of PQS, it was
also suggested that active LasR protein is required for PQS production
and that RhlR is required for PQS bioactivity (22). The
latter conclusion was based on the fact that exogenous PQS induced a
lasB'-lacZ fusion in a lasR mutant but not in a lasR rhlR double mutant. This inability to activate
lasB in the absence of RhlR suggested that PQS may be acting
directly or indirectly through rhl quorum sensing. While PQS
appeared to be an integral part of the P. aeruginosa
quorum-sensing hierarchy, its exact role in cell-to-cell signaling was
not apparent. To determine if PQS was affecting the components of
rhl or las quorum sensing, we monitored -Gal
activity in strain PAO-R1 (lasR) containing rhlI'-lacZ (pLPRI), rhlR'-lacZ (pPCS1002),
lasI'-lacZ (pPCS223), or lasR'-lacZ (pPCS1001)
reporter fusions. (The lasR mutant strain PAO-R1 was used
because it does not produce PQS [22], which allows the
effects of exogenously added PQS to be determined.) These experiments
produced a very interesting result. We discovered that PQS caused a
major induction of rhlI'-lacZ in strain PAO-R1(pLPRI) (Fig. 1). The addition of 50 µM PQS to
this strain led to the production of 48,428 ± 7,610 Miller units
of -Gal activity, a notable increase over the 2,380 ± 611 Miller units of -Gal activity produced in the absence of PQS. In
contrast, the lasI'-lacZ fusion was not affected by
exogenously added PQS, and as expected, -Gal expression from strain
PAO-R1 containing the vector control, pLP170, was unaffected by the
addition of PQS (Fig. 1). This suggested that the production of the
C4-HSL signal, but not the 3-oxo-C12-HSL signal, was positively regulated by PQS. It should be noted here that
the induction of rhlI caused by the addition of PQS to
strain PAO-R1(pLPRI) shown in Fig. 1 (48,428 ± 7,610 Miller
units) does not fully complement rhlI'-lacZ expression to
the level seen in the wild-type strain containing pLPRI (139,797 ± 10,291 Miller units [see Table 2]). This indicates that either
LasR or a LasR-controlled factor (in addition to PQS) is required for
complete induction of rhlI in P. aeruginosa. We
also found that the expression of lasR'-lacZ and
rhlR'-lacZ increased approximately twofold in the presence
of PQS (Fig. 1). This was interesting because the activation of
lasR by a LasR-controlled factor such as PQS indicates that PQS may be part of a positive feedback loop within the quorum-sensing hierarchy. However, we must point out that both lasR and
rhlR are partially expressed in the absence of PQS and LasR
(Fig. 1), demonstrating that other factors are important for their
expression.
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FIG. 1.
Effect of PQS on expression of quorum-sensing components
in P. aeruginosa. Cultures of P. aeruginosa
strain PAO-R1 (lasR) containing the indicated plasmid were
grown for 18 h in the presence (black bars) or absence (hatched
bars) of 50 µM PQS and assayed for -Gal activity. Results are
expressed in Miller units ± n1 and are the means
for duplicate -Gal assays from at least three separate experiments.
Reporter fusions contained on plasmids: pLPRI, rhlI'-lacZ;
pPCS223, lasI'-lacZ; pPCS1001, lasR'-lacZ;
pPCS1002, rhlR'-lacZ; pLP170, control vector with
promoterless lacZ.
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The results presented in Fig.
1 show that the addition of PQS had the
greatest effect on the expression of
rhlI compared to
the
other quorum-sensing system genes. It has previously been
reported that
rhlI is positively regulated by both
C
4-HSL-RhlR
and 3-oxo-C
12-HSL-LasR
(
9). To learn more about the factors
affecting
rhlI induction, we monitored the expression of
rhlI'-lacZ from plasmid pLPRI contained in the
P. aeruginosa wild-type strain
PAO1 and the defined mutant strains
PDO100 (
rhlI) and PAO-R1 (
lasR).
In the presence
or absence of C
4-HSL and/or PQS, the expression
of
rhlI'-lacZ in strain PDO100(pLPRI) was very similar to
that
in the wild-type strain (Table
2). This indicated that both
C
4-HSL
and PQS did not affect
rhlI expression in
an
rhlI mutant, implying
that elements capable of inducing
full
rhlI expression were present
in strain PDO100
(
rhlI). However, examination of the expression
of
rhlI'-lacZ in the
lasR mutant strain PAO-R1
indicated that
both C
4-HSL and PQS are important regulators
of
rhlI. The addition
of 5 µM C
4-HSL or 50 µM PQS to strain PAO-R1(pLPRI) caused the
expression of
rhlI'-lacZ to be 20 or 35%, respectively, of that
seen in
strain PAO1(pLPRI) (Table
2). Most interestingly, the
addition of
both C
4-HSL and PQS caused
rhlI'-lacZ to be
expressed
at approximately the wild-type level, indicating that these
signals
cooperatively effect
rhlI expression. Taken
together, the data
presented in Fig.
1 and Table
2 indicate that
rhlI expression
falls under the control of both PQS and
C
4-HSL. In addition, these
data confirm the results of
Latifi et al. (
9), who reported
that both the
las
and
rhl quorum-sensing systems affect the expression
of
rhlI.
PQS and C4-HSL cooperatively induce
lasB.
Previous data have shown that three
intercellular signals, 3-oxo-C12-HSL,
C4-HSL, and PQS, are each capable of activating lasB in P. aeruginosa (15, 17,
22). The fact that these signals are not produced independently
of each other has made it difficult to determine the role of each
individual signal with regard to lasB activation. Research
focused on the role of PQS in lasB expression had indicated
that lasB induction by PQS required a functional
rhl quorum-sensing system (22). This led us to speculate that PQS and C4-HSL were functioning in a
cooperative manner to activate lasB. In order to determine
whether C4-HSL and PQS have cooperative effects on
lasB expression, the activation of lasB'-lacZ in
strains PDO100 and PAO-R1 was monitored in the presence of PQS and/or
C4-HSL. In strain PAO-R1, PQS caused lasB'-lacZ to be induced to 28% of the wild-type level seen in strain
PAO1(pTS400) (Table 3). The addition
of C4-HSL alone had a minor effect on lasB'-lacZ
in this strain, but the addition of C4-HSL and PQS together
caused lasB'-lacZ to be induced to 58% of the wild-type level (Table 3). This indicated that these two signals had a cooperative effect on lasB induction. A similar effect
was seen in strain PDO100(pTS400), where the lack of a
functional rhl quorum-sensing system caused
lasB'-lacZ to be expressed at 36% of the wild-type level
seen in strain PAO1(pTS400) (Table 3). The addition of PQS alone
caused an increase of lasB'-lacZ expression to 64% of the
wild-type level, and the addition of C4-HSL alone restored lasB'-lacZ expression to the expected wild-type level (Table
3). Addition of PQS and C4-HSL together had an additive
effect on the induction of lasB'-lacZ, which was expressed
at approximately twice the wild-type level seen in strain
PAO1(pTS400).
PQS is not constitutively produced.
The production of the
C4-HSL and 3-oxo-C12-HSL signals is initiated
during the log phase of growth. Pearson et al. (16) purified
3-oxo-C12-HSL from late-log-phase cultures of strain PAO1,
and C4-HSL has been isolated from extracts of
early-stationary-phase cultures of strain PAO1 (17). It has
also been shown that lasR and rhlR are induced
during the last half of log-phase growth (20). These data
combined with the fact that the production of PQS required active LasR
led us to speculate that PQS would be produced during the late log
phase of growth. In order to learn more about the production of PQS, we
monitored its synthesis throughout the growth cycle. The PQS-producing
strain PAO-JP2(pECP39) (22) was grown in PTSB for 48 h,
and crude PQS was recovered from aliquots removed at specific intervals.
The results presented in Fig.
2 indicate
that PQS was not found in strain PAO-JP2(pECP39) culture medium until
the end of
the log phase of growth. The maximal amount of this signal
was
found in cultures that were in the late stationary phase of growth
(30 to 42 h after inoculation), and the concentration decreased
after 48 h of growth (Fig.
2A). These results showed that PQS
was
produced maximally long after the
las and
rhl
quorum-sensing
systems had been activated, which suggested that
its production
required a factor, in addition to the
las quorum-sensing system,
that is not available
until the stationary phase of growth. These
results are
especially interesting when one considers that the
genes
controlled by the
las quorum-sensing system will be
induced
in strain PAO-JP2(pECP39) because the
autoinducer-independent
LasR encoded by pECP39 is expressed
constitutively (data not shown).
The determination of CFU and
A660 for cultures of strain
PAO-JP2(pECP39)
indicated that bacteria were viable and in the
stationary phase
of growth from approximately 8 to 48 h after
inoculation (Fig.
2B). The CFU and optical density of strain
PAO-JP2(pECP39) were
very similar throughout the growth curve to those
of the wild-type
strain PAO1 (Fig.
2B), indicating that strain
PAO-JP2(pECP39)
was growing normally.
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FIG. 2.
PQS production is initiated in early stationary phase.
(A) PQS bioassays (see Materials and Methods) were performed on culture
supernatant extracts prepared throughout the growth cycle of P. aeruginosa strain PAO-JP2(pECP39). Results were derived from
duplicate -Gal assays from at least four separate experiments and
are expressed as the mean percentage + n1 of the
maximal activation seen during each separate growth curve experiment.
(B) Viability and optical density curves for strains PAO-JP2(pECP39)
(closed symbols) and PAO1 (open symbols). Cultures were sampled at
various times during the growth cycle, and optical density (absorbance
at 660 nm) was determined (squares). Samples were also serially diluted
and plated to determine CFU per milliliter (triangles). Data are from
at least two separate experiments performed in duplicate and are
presented as the mean ± n1.
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DISCUSSION |
We have discovered that the intercellular signal PQS controls the
rhl quorum-sensing system at a transcriptional level. PQS was found to have a major positive effect on rhlI induction
and lesser positive effects on the induction of rhlR and
lasR (Fig. 1). These results, along with previous data which
showed that PQS production required an active LasR protein
(22), indicate that PQS may act as an additional connecting
signal between the las and rhl quorum-sensing
systems by transcriptionally regulating the autoinducer synthase gene,
rhlI. This would be the third link between these two
systems. LasR and 3-oxo-C12-HSL were shown to positively
regulate the transcription of rhlR (9, 20) and rhlI (9) in P. aeruginosa and
Escherichia coli, and 3-oxo-C12-HSL posttranslationally affected RhlR by blocking the interaction of
C4-HSL and RhlR in E. coli (20). The
purpose of PQS acting as an additional linking signal between the two
quorum-sensing systems is not known. Speculatively, the upregulation of
rhlI by PQS (which implies a subsequent increase in
C4-HSL production) may be necessary to overcome the
inhibitory effect of 3-oxo-C12-HSL on the rhl
quorum-sensing system. It is also interesting that Pearson et al.
(19) showed that 3-oxo-C12-HSL accumulated
inside E. coli cells, while C4-HSL freely
diffused to reach an internal-external equilibrium. This could lead to
an imbalance of autoinducer concentration that would require the
upregulation of rhlI in order to provide enough
intracellular C4-HSL to compete with
3-oxo-C12-HSL for binding to RhlR.
Another interesting finding with regard to rhlI regulation
is that it was induced by PQS or C4-HSL in our
lasR mutant, but neither signal had an effect in our
rhlI mutant (Table 2). Additionally, when added together PQS
and C4-HSL had a cooperative effect on rhlI
induction in strain PAO-R1 (lasR) (Table 2). The reason that
rhlI expression was not affected in strain PDO100
(rhlI) is not clear, but there is a plausible explanation.
Since both PQS and the las quorum-sensing system have been
shown to regulate rhlI (Fig. 1) (9), it is most
likely that these elements are able to complement the rhlI
mutation with regard to rhlI'-lacZ expression. Whether this
theory is correct remains to be proven, but it is apparent that
rhlI regulation is quite complex and probably involves
multiple layers of control, perhaps working at different stages of
growth (see below).
We also learned that PQS and C4-HSL cooperatively induce
lasB. Previous reports have shown that lasB
transcription is positively regulated by all three P. aeruginosa intercellular signals (15, 17, 22). In
addition, we knew that the induction of lasB by PQS required
a functional rhl quorum-sensing system (22).
Therefore, we examined the effect of adding both PQS and
C4-HSL to strains PAO-R1 and PDO100 containing pTS400
(Table 3). In both strains, PQS and C4-HSL had a
cooperative effect on the induction of lasB. In strain
PAO-R1(pTS400) the two signals had a synergistic effect on
lasB induction, and in strain PDO100(pTS400) the
signals' effect was additive. The reason for this difference is not
clear, but in either case, lasB'-lacZ was induced to a
greater level in the presence of both signals than with either
individual signal. This indicates that the induction of lasB
requires a complex chain of events that we are continuing to learn about.
Finally, our analysis of PQS production indicated that this signal was
produced much later in the growth cycle than a typical quorum-sensing
signal. The concentration of PQS in culture medium was negligible in
the late log phase of growth and was at a maximum late in the
stationary phase of growth (Fig. 2). PQS was most abundant between 30 and 42 h of growth and had decreased after 48 h of growth
(Fig. 2). This indicated that strain PAO-JP2(pECP39) either made less
PQS after 48 h of growth or produced a factor capable of degrading
PQS at that time. Nevertheless, it is apparent that PQS is not involved
in sensing cell density, because the signal is produced at a time after
cell density has become stable. This leads one to ponder an interesting
question. Given that C4-HSL is produced during the log
phase of growth and PQS is not produced until late in the stationary
phase of growth, then what is the purpose of PQS inducing
rhlI? We speculate that PQS may induce rhlI in
order to further upregulate the rhl quorum-sensing system. This could be beneficial to the organism, since the rhl
quorum-sensing system has been shown to control the production of
elastase, alkaline protease, and the biosurfactant rhamnolipid (2,
8, 12, 17). The production of proteases at a later stage of
growth could help increase the availability of nutrients during
infections because of the tissue-destroying capabilites of these
enzymes. At the same time, rhamnolipid helps cells to utilize
long-chain fatty acids as sources of carbon (11), which
would benefit bacteria that have depleted available nutrients. These
theories lead us to conclude that P. aeruginosa may use PQS
as a signal to induce genes controlled by the rhl
quorum-sensing system in order to respond to stress encountered by
late-stationary-phase cultures.
As more is learned about the quorum-sensing hierarchy of P. aeruginosa, it becomes clear that this is an extremely complex signal transduction pathway. To help clarify the circuitry of these
interrelated systems, we have provided a schematic diagram that
summarizes our present level of understanding (Fig.
3). While the effects of PQS are
intriguing, we are only beginning to understand how this intercellular
signal fits in the grand scheme of P. aeruginosa quorum
sensing. The ability of PQS to induce an important virulence factor
gene (lasB) and genes for quorum-sensing components
(rhlI, rhlR, and lasR) indicates that
understanding its role in quorum sensing will be a key to determining
its effect on virulence.
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FIG. 3.
Model of the P. aeruginosa quorum-sensing
hierarchy. The quorum-sensing cascade begins with the induction of the
las quorum-sensing system when cells reach a threshold
density. Vfr induces lasR (1), and the
concentration of 3-oxo-C12-HSL increases to the point where
it binds to and activates LasR. The LasR-3-oxo-C12-HSL
complex induces genes controlled by the las quorum-sensing
system, including a negative regulator gene (rsaL)
(3), rhlR, and an unidentified gene required for
PQS production. PQS either directly or indirectly induces
rhlI, which leads to the production of C4-HSL
that binds to and activates RhlR. The RhlR-C4-HSL complex
can then induce genes controlled by the rhl quorum-sensing
system. At this time it is not known whether PQS is capable of directly
activating RhlR or acts through another regulator. (Two additional
unanalyzed LuxR homologs, which may play a role in the activity of PQS,
are encoded by P. aeruginosa [www.pseudomonas.com].) Genes
and proteins are indicated by thick arrows and unfilled circles,
respectively. Plus or minus symbols indicate transcriptional activation
or repression of the gene(s) at the end of an arrow, respectively.
Blocking of the association between RhlR and C4-HSL by
3-oxo-C12-HSL is indicated by a minus symbol next to the
arrow between 3-oxo-C12-HSL and C4-HSL at the
bottom of the figure. Question marks indicate an unknown member(s) of
the PQS synthesis pathway that is affected by
LasR-3-oxo-C12-HSL.
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ACKNOWLEDGMENTS |
This work was supported by research grants from the Cystic
Fibrosis Foundation (grant PESCI99I0 to E. C. Pesci), the American Lung Association of North Carolina (to E. C. Pesci), the North Carolina Biotechnology Center (to E. C. Pesci), and the NIH (grant R01-AI33713 to B. H. Iglewski).
We thank C. J. Smith, T. deKievit, R. Smith, M. W. Calfee, E. Batten, and C. S. Pesci for help in manuscript
preparation and thoughtful insight.
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FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, East Carolina University School of
Medicine, BT 132, 600 Moye Blvd., Greenville, NC 27858. Phone: (252)
816-2351. Fax: (252) 816-3535. E-mail:
epesci{at}brody.med.ecu.edu.
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Journal of Bacteriology, May 2000, p. 2702-2708, Vol. 182, No. 10
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Abstract
Introduction
