Editing Quorum sensing (section)

===Evolution===

====Sequence analysis====
The majority of quorum sensing systems that fall under the "two-gene" (an autoinducer synthase coupled with a receptor molecule) paradigm as defined by the ''[[Vibrio fischeri]]'' system occur in the [[gram-negative]] [[Pseudomonadota]]. A comparison between the Pseudomonadota [[phylogeny]] as generated by [[16S ribosomal RNA]] sequences and phylogenies of LuxI-, LuxR-, or LuxS-homologs shows a notably high level of global similarity. Overall, the quorum sensing genes seem to have diverged along with the Pseudomonadota phylum as a whole. This indicates that these quorum sensing systems are quite ancient, and arose very early in the Pseudomonadota lineage.<ref name="gray-2001">{{cite journal | vauthors = Gray KM, Garey JR | title = The evolution of bacterial LuxI and LuxR quorum sensing regulators | journal = Microbiology | volume = 147 | issue = Pt 8 | pages = 2379–2387 | date = August 2001 | pmid = 11496014 | doi = 10.1099/00221287-147-8-2379 | doi-access = free }}</ref><ref name="lerat-2004">{{cite journal | vauthors = Lerat E, Moran NA | title = The evolutionary history of quorum-sensing systems in bacteria | journal = Molecular Biology and Evolution | volume = 21 | issue = 5 | pages = 903–913 | date = May 2004 | pmid = 15014168 | doi = 10.1093/molbev/msh097 | doi-access = free }}</ref>

LuxI and LuxR have coevolved through a long history of horizontal gene transfer (HGT) events. An early study reconciling their gene trees with the rRNA tree suggested frequent HGT events for both LuxI and LuxR, indicating that they are horizontally transferred together and coevolve due to their functional dependency.<ref name="gray-2001" /> Similarly, in QS systems in bacteria associated with ''Populus deltoides'', the gene trees for ''luxI'' and ''luxR'' show high topological similarity, indicating coevolution of cognate pairs.<ref name=":9">{{Cite journal |last1=Schaefer |first1=Amy L. |last2=Lappala |first2=Colin R. |last3=Morlen |first3=Ryan P. |last4=Pelletier |first4=Dale A. |last5=Lu |first5=Tse-Yuan S. |last6=Lankford |first6=Patricia K. |last7=Harwood |first7=Caroline S. |last8=Greenberg |first8=E. Peter |date=2013-09-15 |title=LuxR- and LuxI-Type Quorum-Sensing Circuits Are Prevalent in Members of the Populus deltoides Microbiome |journal=Applied and Environmental Microbiology |language=en |volume=79 |issue=18 |pages=5745–5752 |doi=10.1128/AEM.01417-13 |issn=0099-2240 |pmc=3754149 |pmid=23851092|bibcode=2013ApEnM..79.5745S }}</ref> In addition to horizontal transfer of complete LuxI/LuxR-type QS systems, many Proteobacteria genomes exhibit an excess of LuxR genes or cases with only LuxR but not LuxI, acquired from different sources via HGT.<ref name=":9" /> Due to the frequent transfer of functional pairs of homologs (i.e., LuxI/LuxR-type systems from multiple independent sources), it is possible that the regulatory hierarchy formed by the LuxI/LuxR and RhlR-RhlI systems is a result of sequential integration of circuits obtained from different sources, due to interactions between multiple homologs.<ref name="gray-2001" /> Interestingly, LuxI genes have likely undergone horizontal gene transfer from Proteobacteria to other lineages, as they have been detected in Nitrospira lineage II.<ref>{{Cite journal |last1=Mellbye |first1=Brett L. |last2=Spieck |first2=Eva |last3=Bottomley |first3=Peter J. |last4=Sayavedra-Soto |first4=Luis A. |date=2017-11-15 |editor-last=Parales |editor-first=Rebecca E. |title=Acyl-Homoserine Lactone Production in Nitrifying Bacteria of the Genera Nitrosospira, Nitrobacter, and Nitrospira Identified via a Survey of Putative Quorum-Sensing Genes |journal=Applied and Environmental Microbiology |language=en |volume=83 |issue=22 |doi=10.1128/AEM.01540-17 |issn=0099-2240 |pmc=5666142 |pmid=28887424|bibcode=2017ApEnM..83E1540M }}</ref>

In quorum sensing genes of [[Gammaproteobacteria]], which includes ''[[Pseudomonas aeruginosa]]'' and ''[[Escherichia coli]]'', the LuxI/LuxR genes form a functional pair, with LuxI as the auto-inducer synthase and LuxR as the receptor. Gammaproteobacteria are unique in possessing quorum sensing genes, which, although functionally similar to the LuxI/LuxR genes, have a markedly divergent sequence.<ref name="lerat-2004"/> This family of quorum-sensing [[homology (biology)|homologs]] may have arisen in the Gammaproteobacteria ancestor, although the cause of their extreme sequence divergence yet maintenance of functional similarity has yet to be explained. In addition, species that employ multiple discrete quorum sensing systems are almost all members of the Gammaproteobacteria, and evidence of horizontal transfer of quorum sensing genes is most evident in this class.<ref name="gray-2001"/><ref name="lerat-2004"/>

====Interaction of quorum-sensing molecules with mammalian cells and its medical applications====
Next to the potential antimicrobial functionality, quorum-sensing derived molecules, especially the peptides, are being investigated for their use in other therapeutic domains as well, including immunology, central nervous system disorders and oncology. Quorum-sensing peptides have been demonstrated to interact with cancer cells, as well as to permeate the blood–brain barrier reaching the brain parenchyma.<ref>{{cite journal | vauthors = De Spiegeleer B, Verbeke F, D'Hondt M, Hendrix A, Van De Wiele C, Burvenich C, Peremans K, De Wever O, Bracke M, Wynendaele E | display-authors = 6 | title = The quorum sensing peptides PhrG, CSP and EDF promote angiogenesis and invasion of breast cancer cells in vitro | journal = PLOS ONE | volume = 10 | issue = 3 | pages = e0119471 | year = 2015 | pmid = 25780927 | pmc = 4363635 | doi = 10.1371/journal.pone.0119471 | bibcode = 2015PLoSO..1019471D | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wynendaele E, Verbeke F, D'Hondt M, Hendrix A, Van De Wiele C, Burvenich C, Peremans K, De Wever O, Bracke M, De Spiegeleer B | display-authors = 6 | title = Crosstalk between the microbiome and cancer cells by quorum sensing peptides | journal = Peptides | volume = 64 | pages = 40–48 | date = February 2015 | pmid = 25559405 | doi = 10.1016/j.peptides.2014.12.009 | hdl-access = free | s2cid = 28064836 | hdl = 2263/59248 }}</ref><ref>{{cite journal | vauthors = Wynendaele E, Verbeke F, Stalmans S, Gevaert B, Janssens Y, Van De Wiele C, Peremans K, Burvenich C, De Spiegeleer B | display-authors = 6 | title = Quorum Sensing Peptides Selectively Penetrate the Blood-Brain Barrier | journal = PLOS ONE | volume = 10 | issue = 11 | pages = e0142071 | date = Nov 2015 | pmid = 26536593 | pmc = 4633044 | doi = 10.1371/journal.pone.0142071 | bibcode = 2015PLoSO..1042071W | doi-access = free }}</ref>