AHL-Driven Quorum-Sensing Circuits: Their Frequency and Function Among the Proteobacteria

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The ISME Journal (2008) 2, 345–349 & 2008 International Society for Microbial Ecology All rights reserved 1751-7362/08 $30.00 www.nature.com/ismej COMMENTARY AHL-driven quorum-sensing circuits: their frequency and function among the Proteobacteria

Rebecca J Case, Maurizio Labbate and Staffan Kjelleberg

The ISME Journal (2008) 2, 345–349; doi:10.1038/ this article, we use all current bacterial genomes to ismej.2008.13; published online 14 February 2008 examine the frequency of AHL-QS among these bacteria, and the surprising number of bacteria with the genetic potential for eavesdropping on AHL It is now apparent that bacteria utilize regulatory signals from other bacteria. systems called quorum sensing (QS) to sense their population density. Such systems are dependant on the production of signaling molecules that activate Frequency of QS among genome- specific genes when the signal reaches a critical sequenced bacteria threshold concentration. Such QS-regulated genes produce phenotypes that require coordinate beha- The AHL-QS system is characterized by two core vior to convey competitive advantage to the popula- proteins, the LuxI-type protein (the AHL synthase), tion (such as biofilm formation and pathogenesis). and the LuxR-type protein (the response regulator). The best-characterized QS system is that driven by Almost all AHL-producing bacteria rely on only acylated homoserine lactone (AHL) molecules. these two protein families for active QS circuits; Quorum sensing-regulated phenotypes are di- however, exceptions exist such as the LuxM AHL verse; however, their evolutionary selection is synthase in Vibrio harveyi and the putative HdtS based on the competitive advantage conveyed AHL synthase identified in Pseudomonas fluore- by coordinating gene expression with the establish- scens F113, both of which replace the LuxI-type ment of a quorum. Population density and coordi- AHL synthase. nated gene expression are coupled for either (1) the Using the 512 completed bacterial genomes as a multicellular characteristic of behaviors such as cell data set (http://www.ncbi.nlm.nih.gov/sutils/gen- differentiation (for example swarming, biofilm for- om_table.cgi on 26 July 2007), LuxI and LuxR mation), or (2) the fitness benefit of many individual homologs were found only within proteobacterial cells simultaneously expressing the same phenotype genomes. Complete QS circuits (that is, containing (for example virulence factors, luminescence). QS at least one LuxI and LuxR homolog) were identified enables a population to differentiate under favorable from 68 (13%) of the bacterial genomes, or 26% of conditions where the population is dense enough to the 265 proteobacterial genomes (Table 1). When support the division and coordination of labor into compared to metagenomic data, these statistics seem subpopulations. In undifferentiated populations, QS high. The predicted proteome of the marine meta- coordinates gene expression so that it is simul- genome (Rusch et al., 2007) recovered 20 LuxI and taneous for cells within the population. 31 LuxR homologs, and a 130-genome equivalent In both scenarios, having QS regulation provides a metagenomic library of Alaskan sediments competitive advantage for a population to both recovered a single clone capable of inducing an produce and respond to QS molecules. A selective AHL reporter and containing a luxI homolog pressure also exists for non-QS bacteria to sense and (Williamson et al., 2005). However, all of these respond to QS molecules produced within the figures are biased, for instance whole-organism community. Examples of QS bacteria and bacteria genomics rely on culturing, there is a sampling bias able to detect and respond to exogenous signals are of filtered seawater used to construct the marine found in the literature; however, the frequency of metagenome (mainly free-living bacteria are repre- QS and QS cheaters in the environment is sented in the metagenome), there are limitations in poorly documented. With the growing number of expressing environmental DNA from metagenomic bacterial genomes sequenced, especially genomes libraries and AHL reporters are unable to detect the of nonclinically isolated bacteria, it may not be structural diversity of AHLs. Whatever be the surprising that the number of genomes containing limitations of our methodologies, the number of homologs of AHL-QS circuitry is ever growing. In bacteria in which we identify QS is ever increasing, Commentary 346 Table 1 Bacterial genomes with AHL-driven quorum-sensing Table 1 Continued networks Genome No. of LuxI No. of LuxR a a Genome No. of LuxI No. of LuxR homologs homologs homologsa homologsa Sphingopyxis alaskensis RB2256 23 Acidovorax avenae subsp. citrulli 11Sphingomonas wittichii RW1 13 AAC00-1 Vibrio fischeri ES114 1 1 Acinetobacter baumannii ATCC 11Yersinia enterocolitica subsp. 12 17978 Enterocolitica 8081 Aeromonas hydrophila subsp. 12Y. pestis Antiqua 2 2 hydrophila ATCC 7966 Y. pestis bv. Microtus 91001 2 2 A. salmonicida subsp. salmonicida 12Y. pestis CO92 2 2 A449 Y. pestis KIM 2 2 Agrobacterium tumefaciens C58 15Y. pestis Nepal516 2 2 Bradyrhizobium japonicum 13Y. pestis Pestoides F 12 USDA 110 Y. pseudotuberculosis IP 32953 2 2 Bradyrhizobium sp. BTAi1 34 Bradyrhizobium sp. ORS278 1 1 Abbreviation: AHL, acylated homoserine lactone. Burkholderia cenocepacia AU 1054 13aHomologs of LuxI and LuxR were identified using the following B. cenocepacia HI2424 13definitions: a LuxI homolog is 190–230 amino acids long and defined À6 B. cepacia AMMD 25by a BLASTP e-value greater than 10 to a characterized LuxI-type AHL synthase. A LuxR homolog is 200–240 amino acids long, has a B. mallei ATCC 23344 25 À6 B. mallei NCTC 10229 25BLASTP e-value greater than 10 to a characterized LuxR-type, AHL B. mallei NCTC 10247 24response regulator and shows homology to an AHL-binding domain within 30 amino acids of its N terminus and homology to the GerE- B. mallei SAVP1 12type DNA-binding domain at the C terminus. Some two-component B. pseudomallei 1106a 35response regulators have DNA-binding domains homologous to the B. pseudomallei 1710b 36GerE-type; however, they were excluded as their ligand-binding B. pseudomallei 668 35domain lacked homology to an AHL-binding domain. B. pseudomallei K96243 36 Burkholderia sp. 383 12 B. thailandensis E264 37 B. vietnamiensis G4 3 3 B. xenovorans LB400 23with genome sequencing a major source of this Chromobacterium violaceum 11discovery. ATCC 12472 Among the bacterial genomes in which QS is Erwinia carotovora subsp. 12identified, several are surprising. The role of QS Atroseptica SCRI1043 Geobacter uraniumreducens Rf4 1 1 among several such environmental bacterial isolates Jannaschia sp. CCS1 13is unknown and unlikely to be predicted from Mesorhizobium loti MAFF303099 4 4 model QS organisms, which are generally pathogens Mesorhizobium sp. BNC1 12or symbionts of a eukaryotic host. Environmental Nitrobacter hamburgensis X14 3 3 strains identified here with complete QS circuits are N. winogradskyi Nb-255 1 1 Nitrosospira multiformis 11not known to be pathogens or symbionts; rather they ATCC25196 play important roles in biogeochemical cycles Pseudoalteromonas atlantica T6c 12(for example the uranium-reducing Geobacter Pseudomonas aeruginosa PA7 23uraniumreducens and the oligotroph Sphingopyxis P. aeruginosa PAO1 24 P. aeruginosa UCBPP-PA14 24alaskensis). P. syringae pv. phaseolicola 1448A 13 P. syringae pv. syringae B728a 13 P. syringae pv. tomato DC3000 12 Ralstonia solanacearum GMI1000 2 2 Extra LuxR-type proteins Rhizobium etli CFN 42 39 R. leguminosarum bv. viciae 3841 37The number of LuxI- and LuxR-type proteins in a Rhodobacter sphaeroides 2.4.1 12given bacterium is not always equal. In fact, 45 R. sphaeroides ATCC 17025 12of the 68 (66%) bacteria identified here with QS R. sphaeroides ATCC 17029 14circuits have more LuxR than LuxI homologs Rhodopseudomonas palustris 12 BisA53 (Table 1—numbers in bold). In a QS circuit, a R. palustris BisB18 23LuxI-type protein has a specific LuxR-type protein R. palustris BisB5 2 2 that binds its AHL, but there are often ‘extra’ LuxR- R. palustris CGA009 1 1 type proteins. For example, Pseudomonas aerugi- R. palustris HaA2 2 2 nosa contains two QS circuits (LasI/R and RhlI/R) Rhodospirillum rubrum ATCC 11 11170 but also contains QscR and a fourth LuxR-type Roseobacter denitrificans OCh 114 12protein identified here (Figure 1b). It has been Saccharophagus degradans 2–40 1 1 suggested that these extra LuxR-type proteins are Silicibacter pomeroyi DSS-3 25orphans (Fuqua, 2006); however, as they belong to a Sinorhizobium medicae WSM419 37 S. meliloti 1021 15characterized protein family (AHL response regula- Sodalis glossinidius morsitans 12tors) and the biological role of several has been described (Wang et al., 1991; Smith and Ahmer,

The ISME Journal Commentary 347 2003; Lee et al., 2006, 2007; Lequette et al., 2006), Burkholderia xenovorans LB400 (YP 553061) B. cepacia AMMD (YP 776119) they cannot be considered orphans. 78 Burkholderia sp. 383 (YP 371614) 100 99 B. cenocepacia HI2424 (YP 838485) The best-characterized of these extra LuxR-type B. cenocepacia AU 1054 (YP 623375) 100 B. thailandensis E264 (YP 439945) proteins in a bacterium with complete QS circuits is B. pseudomallei 1710b (YP 337392) 99 B. mallei NCTC 10229 (YP 0010239) BisR in Rhizobium leguminosarum bv. viciae. R. B. pseudomallei K96243 (YP 110689) B. mallei ATCC 23344 (YP 105811) leguminosarum bv. viciae has three QS networks, B. cepacia AMMD (YP 777918) Ralstonia solanacearum GMI1000 (NP 521406) cin, rai and tra, with an additional LuxR-type B. thailandensis E264 (YP 439706) B. pseudomallei 1106a (YP 001075256) protein, BisR. BisR negatively regulates cin QS, 100 B. mallei NCTC 10247 (YP 001078154) 100 B. pseudomallei 668 (YP 001062292) thereby maintaining a low endogenous 3O-C14-HSL B. mallei NCTC 10229 (YP 001024423) B. mallei SAVP1 (YP 989940) B. pseudomallei 1710b (YP 337635) concentration (as CinI synthesizes 3O-C14-HSL) 74 B. pseudomallei K96243 (YP 110896) (Danino et al., 2003). As 3O-C14-HSL is also the B. mallei ATCC 23344 (YP 105961) B. cepacia AMMD (YP 776003) cognate AHL for BisR, BisR requires exogenous 3O- Burkholderia sp. 383 (YP 371810) 95 B. vietnamiensis G4 (YP 001117674) C14-HSL for it to positively regulate traR, which B. cenocepacia HI2424 (YP 838351) B. cenocepacia AU 1054 (YP 623508) induces conjugal transfer (Danino et al., 2003). The Pseudomonas aeruginosa PA7 (YP 001347034) P. aeruginosa UCBPP-PA14 (YP 789670) incorporation of BisR into the QS regulatory 100 P. aeruginosa PAO1 (NP 252167) RhlR B. thailandensis E264 (YP 439427) network allows R. leguminosarum bv. viciae to B. pseudomallei 1106a (YP 001075611) 100 B. pseudomallei 668 (YP 001062648) 100 B. pseudomallei 1710b (YP 335301) induce conjugal transfer only when a quorum of B. pseudomallei K96243 (YP 111189) 3O-C14-HSL-producing bacteria (the recipients) is R. solanacearum GMI1000 (NP 522339) B. cepacia AMMD (YP 777789) 93 B. pseudomallei K96243 (YP 108943) 80 B. thailandensis E264 (YP 442349) B. mallei NCTC 10247 (YP 001081227) 100 B. mallei NCTC 10229 (YP 001028861) Sinorhizobium meliloti 1021 (NP 386820) B. pseudomallei 1106a (YP 001066980) Rhizobium leguminosarum bv. viciae 3841 (YP 766287) B. pseudomallei 668 (YP 001059696) 62 R. leguminosarum bv. viciae 3841 (YP 769108) B. mallei SAVP1 (YP 993677) 100 R. etli CFN 42 (YP 470573) B. pseudomallei 1710b (YP 334182) S. medicae WSM419 (YP 001326133) B. mallei ATCC 23344 (YP 102421) 100 S. meliloti 1021 (NP 384934) 77 B. thailandensis E264 (YP 439875) B. vietnamiensis G4 (YP 001115608) Agrobacterium tumefaciens C58 (NP 531407) 96 B. cenocepacia HI2424 (YP 836819) 100A. tumefaciens C58 (NP 353732) B. cenocepacia AU 1054 (YP 624828) R. etli CFN 42 (YP 468692) 100 P. aeruginosa PA7 (YP 001348746) R. leguminosarum bv. viciae 3841 (YP 766531) 100 P. aeruginosa UCBPP-PA14 (YP 791341) 100R. etli CFN 42 (YP 468395) P. aeruginosa PAO1 (NP 250589) QscR S. medicae WSM419 (YP 001326132) P. entomophila L48 (YP 610214) S. meliloti 1021 (NP 384935) P. putida F1 (YP 001269813) 100 100 100 P. putida KT2440 (NP 746756) Bradyrhizobium sp. BTAi1 (YP 001242900) B. thailandensis E264 (YP 440275) 100 Bradyrhizobium sp. ORS278 (YP 001203095) B. mallei NCTC 10229 (YP 001025964) S. medicae WSM419 (YP 001328801) 100 B. pseudomallei 1106a (YP 001074487) 69 R. etli CFN 42 (YP 471472) 95 B. mallei ATCC 23344 (YP 106048) 100 A. tumefaciens C58 (NP 533392) B. mallei NCTC 10247 (YP 001078053) 100 B. pseudomallei K96243 (YP 110332) A. tumefaciens C58 (NP 355660) B. pseudomallei 668 (YP 001061548) S. medicae WSM419 (YP 001325938) B. pseudomallei 1710b (YP 337020) Mesorhizobium loti MAFF303099 (NP 106261) B. xenovorans LB400 (YP 554691) R. leguminosarum bv. viciae 3841 (YP 770451) 100 P. aeruginosa PA7 (YP 001349251) Bradyrhizobium japonicum USDA 110 (NP 767702) 100 P. aeruginosa PAO1 (NP 250121) LasR 61 B. japonicum USDA 110 (NP 767883) 95 P. aeruginosa UCBPP-PA14 (YP 791822) P. fluorescens Pf-5 (YP 262370) Mesorhizobium sp. BNC1(YP 674864) P. syringae pv. phaseolicola 1448A (YP 276356) M. loti MAFF303099 (NP 109411) 100 P. syringae pv. syringae B728a (YP 237284) Bradyrhizobium sp. BTAi1 (YP 001240084) 100 P. syringae pv. tomato DC3000 (NP 794292) Bradyrhizobium sp. BTAi1 (YP 001220570) B. vietnamiensis G4 (YP 001114942) M. loti MAFF303099 (NP 106660) 96 B. xenovorans LB400 (YP 555670) B. thailandensis E264 (YP 439002) R. leguminosarum bv. viciae 3841(YP 771022) 100 100 A. tumefaciens C58 (NP 536252) B. pseudomallei 1106a (YP 001076161) B. mallei NCTC 10247 (YP 001077903) 92 R. etli CFN 42 (YP 471756) 100 B. pseudomallei 668 (YP 001063209) 100 S. medicae WSM419 (YP 001314089) 100 B. mallei NCTC 10229 (YP 001025820) R. leguminosarum bv. viciae 8401 (AAO21112) TraR B. pseudomallei 1710b (YP 335776) S. medicae WSM419 (YP 001314420) B. pseudomallei K96243 (YP 111575) B. mallei ATCC 23344 (YP 106160) 98 Bradyrhizobium sp. BTAi1 (YP 001241092) R. etli CFN 42 (YP 471756) Burkholderia cepacia AMMD (YP 776923) 100 R. leguminosarum bv. viciae 8401 (CAD20930) RaiR P. syringae pv. tomato DC3000 (NP 793635) 82 P. syringae pv. syringae B728a (YP 234708) 3O-C14-HSL 100 Mesorhizobium sp. BNC1 (YP 673968) 77 P. syringae pv. phaseolicola 1448A (YP 273861) R. leguminosarum bv. viciae 8401 (AAO21111) BisR P. syringae pv. phaseolicola 1448A (YP 274051) 100 100 R. etli CFN 42 (YP 471757) 100 P. syringae pv. syringae B728a (YP 234943) P. fluorescens Pf-5 (YP 260729) 61 99 R. leguminosarum bv. viciae 3841 (YP 768957) R. etli CFN 42 (YP 470410) P. entomophila L48 (YP 608439) 100 } 72 100 P. fluorescens PfO-1 (YP 347979) R. leguminosarum bv. viciae 8401 (AAF89989) CinR 100 P. aeruginosa PAO1 (NP 249827) uncharacterised S. medicae WSM419 (YP 001327236) 0.1 99 100 S. meliloti 1021 (NP 385944) P. aeruginosa UCBPP-PA14 (YP 792130) B. japonicum USDA 110 (NP 768520) 83 M. loti MAFF303099 (NP 106527) Figure 1 Continued. S. meliloti 1021 (NP 386921) 100 R. etli CFN 42 (YP 471858) 0.1 88 R. leguminosarum bv. viciae 3841 (YP 765467) established. Figure 1a illustrates the phylogeny of Figure 1 Predicted LuxR-type proteins from Rhizobia and rhizobia and Agrobacterium LuxR-type proteins Agrobacterium genomes (a) and Pseudomonas and Burkholderia with the LuxR-type proteins whose cognate AHL genomes (b). Rhizobium leguminosarum bv. viciae 8401 is is 3O-C14-HSL, forming a monophyletic group. included in (a) as its AHL-QS circuits are characterized (Danino This shows that cross talk between these species is et al., 2003), although its genome is not sequenced. P. aeruginosa PAO1 and R. leguminosarum bv. viciae 8401 LuxR-type proteins due to the close evolutionary relationship of the are given in bold. The number in parentheses found after each 3O-C14-HSL-binding LuxR-type proteins within the taxon name is the accession number for the respective protein rhizobia. sequence. The trees were compiled by maximum likelihood using Another example of an uncoupled LuxR-type PROML. The bootstrap support value displayed above the nodes represents the consensus of maximum likelihood trees obtained protein is QscR in P. aeruginosa. QscR negatively from 100 pseudo-replicates of the original data set (only values regulates both the las and rhl QS system by binding above 50 are displayed). LasR, RhlR and their cognate AHLs (Ledgham et al.,

The ISME Journal Commentary 348 Azoarcus sp. EbN1 (YP 195352) commonly found in soil, and some species within 68 Polaromonas sp. JS666 (YP 552230) Pseudomonas fluorescens Pf-5 (YP 262370) these genera are opportunistic pathogens. Although Xanthomonas axonopodis pv. citri 306 (NP 643297) 97 X. campestris pv. vesicatoria 85-10 (YP 364866) they are from different classes of the Proteobacteria, 91 X. oryzae pv. oryzae MAFF 311018 (YP 450196) 100 100 X. oryzae pv. oryzae KACC10331 (YP 199907) LuxR-type proteins from Burkholderia spp. and 100 X. campestris pv. campestris 8004 (YP 242384) X. campestris pv. campestris ATCC 33913 (NP 638166) Pseudomonas spp. are most related to each 72 P. syringae pv. phaseolicola 1448A (YP 276356) 100 P. syringae pv. tomato DC3000 (NP 794292) other, suggesting that their coding genes have Rhosopseudomonas palustris HaA2 (YP 484040) Burkholderia pseudomallei (YP 334182) been involved in lateral gene transfer (Figure 1b). Photorhabdus luminescens ssp. laumondii TTO1 Erwinia amylovora (AAW78919) (NP 927679) This shared evolutionary history resulting from Escherichia coli B171 (ZP 00709120) E. coli APEC O1 (YP 852971) lateral transfer could facilitate cross talk between E. coli UTI89 (YP 541121) Burkholderia spp. and Pseudomonas spp. E. coli CFT073 (NP 754222) Shigella flexneri 5 8401 (YP 689409) S. flexneri 2a 301 (NP 707803) 100 S. flexneri 2a 2457T (NP 837531) 100 S. sonnei Ss046 (YP 310157) S. boydii Sb227 (YP 407563) E. coli W3110 (AP 002531) Incomplete QS circuits E. coli K12 (NP 416426) 100 E. coli O157:H7 Sakai (NP 310681) E. coli O157:H7 EDL933 (NP 288377) Bacteria exist that contain a LuxR but not LuxI Klebsiella pneumoniae subsp. pneumoniae MGH78578 homolog (that is, lacking complete QS circuits) such 89 (YP 001336067) Enterobacter sp. 638 (YP 001177223) as Brucella melitensis, Salmonella typhimurium and 87 Salmonella enterica subsp. enterica sv. Typhi Ty2 (NP 804754) S. enterica subsp. enterica sv. Typhi CT18 (NP 456513) Escherichia coli. S. typhimurium and E. coli have a 100 S. enterica subsp. enterica sv. Paratyphi A ATCC 9150 S. typhimurium LT2 (NP 460903) (YP 150210) S. enterica subsp. enterica sv. Choleraesuis SC-B67 luxR homolog called sdiA, but do not produce any P. entomophila L48 (YP 610214) (YP 216941) detectable AHLs (Wang et al., 1991; Smith and 100 P. putida F1 (YP 001269813) 100 P. putida KT2440 (NP 746756) Ahmer, 2003). Importantly, SdiA has been shown to B. cepacia AMMD (YP 776003) Ochrobactrum anthropi ATCC 49188 (YP 001368758) respond to exogenous AHLs and regulate virulence 89 Brucella ovis ATCC 25840 (YP 001258220) 100 B. melitensis bv. Abortus 2308 (YP 413678) in S. typhimurium and biofilm formation in E. coli 100 B. abortus bv. 1 9-941 (YP 220957) B. melitensis 16M (NP 540675) (Wang et al., 1991; Smith and Ahmer, 2003; B. suis 1330 (NP 697228) Methylibium petroleiphilum PM1 (YP 001022984) Lee et al., 2007); both phenotypes are important B. pseudomallei K96243 (YP 110332) P. fluorescens Pf-5 (YP 260729) for competition and host interactions. B. cepacia AMMD (YP 776923) Chromobacterium violaceum ATCC 12472 (NP 903760) Why would bacteria without QS contain luxR 73 Geobacter metallireducens GS-15 (YP 384472) homologs in their genome? These luxR homologs are Rhizobium leguminosarum bv. viciae 8401 (AAO21111) B. melitensis 16M (NP 542094) 59 unlikely to be redundant remnants of gene acquisi- 100 O. anthropi ATCC 49188 (YP 001372753) B. ovis ATCC 25840 (YP 001257186) tion or loss as none of the completed bacterial B. melitensis bv. Abortus 2308 (YP 418357) B. abortus biovar 1 9-941 (YP 222926) genomes contain only a luxI homolog. One possible B. suis 1330 (NP 697228) Silicibacter sp. TM1040 (YP 611338) selective pressure to maintain these luxR homologs 100 S. pomeroyi DSS-3 (YP 165634) Roseobacter sp. SK209-2-6 (ZP 01753468) is for sensing and response to QS signals produced 100 Silicibacter sp. TM1040 (YP 613207) Acinetobacter sp. ADP1 (YP 045866) by competing bacteria. The incorporation of exogen- 69 58 P. aeruginosa PAO1 (NP 249827) ous signals into the transcriptional regulation of 100 P. entomophila L48 (YP 608439) 84 P. fluorescens PfO-1(YP 347979) genes mediating species interaction would create 100 Vibrio cholerae O1 bv. eltor N16961 (NP 233273) the potential for bacteria to eavesdrop on QS by 0.1 100 V. cholerae O395 (YP 001215191) competing bacteria and modulate the interaction Figure 2 Predicted LuxR-type proteins from bacterial genomes with its competitor(s). Such phenotypes are regu- that lack complete AHL-QS circuits and nearest neighbours. Fifty- lated by SdiA. three LuxR-type proteins found from 45 bacterial genomes that A phylogenetic survey of all bacterial genomes in lack complete AHL-QS circuits are shown in bold. The number in parentheses found after each taxon name is the accession number the database identified 45 bacteria that contained for the respective protein sequence. The trees were compiled by LuxR homolog(s) but no corresponding AHL maximum likelihood using PROML. The bootstrap support value synthase (Figure 2—sequences in bold). While it is displayed above the nodes represents the consensus of maximum unknown if all LuxR homologs are functional, it likelihood trees obtained from 100 pseudo-replicates of the original data set (only values above 50 are displayed). suggests that eavesdropping on QS bacteria may be prevalent among the Proteobacteria, with 26% of genome-sequenced Proteobacteria with complete 2003). QscR has been shown to affect a distinct QS circuits and another 17% with the potential regulon that is activated by the LasI-generated signal to eavesdrop on AHL-driven QS in other 3O-C12-HSL (Lequette et al., 2006). Furthermore, Proteobacteria. QscR has less specificity for AHL signals and is Given that bacteria rarely live in monoculture but more sensitive to 3O-C10-HSL, an AHL not pro- rather in complex mixed communities, it would not duced by P. aeruginosa, suggesting that QscR may be surprising that bacteria evolve the ability to function by responding to other AHLs produced eavesdrop. The ability to eavesdrop on the quorum by cohabitating microbes (Ledgham et al., 2003; established by another organism and consequently Fuqua, 2006; Lee et al., 2006). We propose that the alter the transcriptome is a level of social sophisti- most-likely exogenous AHL candidates for QscR cation previously not thought to exist among are derived from other Pseudomonas spp. and bacteria. R. leguminosarum bv. viciae eavesdrops Burkholderia spp. Pseudomonas and Burkholderia on its ‘friends’ to delay conjugation until a quorum have a similar life style as ubiquitous organisms is established. Other bacteria may eavesdrop on

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