Multicellular life style:Myxococcus • Gram- soil bacteria • 9.1 MBases genome, one of the largest in microbes • Prey cooperatively on other microbes • Produces lytic enzymes, antibiotics. • Have sophisticated life cycle • At least five signals (signal A, B, C, D, and E) are involved in different stages of the life cycle • diffusible signals, and cell-to-cell physical contact are important for multicellular coordination • “signal A” is a mix of peptides, aminoacids that act in a QS-like manner • “signal C” is a surface protein encoded by a gene
Multicellular life style:Myxococcus ? signal A Nutrient limitation is a cue for making a decision.
Multicellular life style:Myxococcus ? signal A Decision to make a fruiting body or spores: the majority of cells die in either case Nutrient limitation is a cue for making a decision.
Multicellular life style:Myxococcus C signal helps transition from heaps created by a “traffic jam” to a structure. Cells need to be aligned end-to-end ? signal A Decision to make a fruiting body or spores: the majority of cells die in either case Nutrient limitation is a cue for making a decision.
Multicellular life style:Myxococcus 1) the shape of the fruiting body is genetically encoded 2) laboratory growth under asocial conditions eliminates the ability to form fruiting bodies 3) May make “stigmalone” a novel QS signal that synchs up development C signal helps transition from heaps created by a “traffic jam” to a structure. Cells need to be aligned end-to-end ? signal A Decision to make a fruiting body or spores: the majority of cells die in either case Nutrient limitation is a cue for making a decision. signal A is also involved in the coordinated predation
Multicellular lifestyle: Biofilms http://www.socialfiction.org/img/biofilm.jpg
Social Evolution Theory: Direct vs Indirect Benefits • Indirect fitness • Individuals gain inclusive fitness through their impact on reproduction of relatives • Altruistic cooperation • Kin selection: by helping relatives reproduce, genes are passed on • Direct fitness • gain fitness directly by increasing own reproduction
Social Evolution Theory:Cost-Benefit Analysis • Costs of cooperation are clear, benefits not so much • Feeding “cheaters” may fit with kin selection • Cooperating strains out-compete “selfish” mutants in the lab
Bacteriocins • Produced by most bacteria. Abundant • Enzymes with bacterial killing ability • Spiteful: producing cells also at disadvantage, unless have acquired resistance mechanisms • Bacteriocin producing and resistant strains are spatially isolated
Quorum Sensing Is Central to Symbiosis Eberhard, et al., 1981; Crookes et al., Science303:235
Quorum Sensing:Population Density-Dependent Gene Regulation growth Quorum sensing-regulated gene expression time
Behaviors controlled by QS • Structuring of multicellular communities • Stress survival • Production of • Antibiotics • Pigments • Host tissue degrading enzymes
QS signals in Bacteria Signals are diverse, most are synthesized by specific known enzymes
Enzymatic synthesis of QS signals AHL synthase, LuxI-like AI-2 in Gram-, Gram+ bacteria AHLs are common in Gram- bacteria Keller et al.Nature Reviews Microbiology; published online 27 February 2006 | doi:10.1038/nrmicro1383
Detection of QS signals in V. fischeri LuxI = AHL synthase (makes AHLs) LuxR = AHL receptor (detects AHLs) luxCDABE = encodes production of light in V.fischeri Red triangle = AHLs that diffuse in and out
Examples of AHL-mediated QS • Vibrio fischeri • light production • Vibrio cholera • When grows on chitin, can acquire DNA from environment. Requires AHLs to be able to grow on chitin • Pseudomonas aeruginosa • virulence, Fe acquisition, stress response, etc. Over 200 genes • Yersinia enterocolitica • is activated in foods, possibly involved in enzyme production, biofilm formation • Salmonella, E. coli, Shigella • do not make AHLs themselves (have lost the AHL synthase gene) • detect AHLs produced by other bacteria (have gained a new AHL receptor gene)
Other examples of QS in Gram - • AI-2 signal in many G-, G+ bacteria. A universal language? • Non-AHL unknown signals in Xyllela, Xanthomonas (water-, air-, soil- borne pathogens of citrus and grapes) • Volatile esters of fatty acids in Ralstonia, a pathogen that causes wilt in tomato
Quorum sensing in Gram + bacteria • Signals, detection appear more diverse • Gamma-butyrolactone in Streptomyces controls production of aerial hyphae and antibiotics • Myxococcus uses a mixture of aminoacids to initiate sporulation (more later) • Peptide signals in Bacillus, Staph control competence, virulence
Degradation of AHL QS signals • AHLs can be degraded by enzymes produced by soil bacteria: • Bacillus AHL lactonase, AiiA (cleaves lactone ring) • AHL acylases made by several soil bacteria. Cleaves of acyl side chain • Ecological functions of degrading AHLs • C, N sources • “scrambling” communication in other bacteria. • turn-over of the signal
QS and Fratricide • Fratricide = killing off siblings • Bacillus subtilis can form spores (resting structures) in response to nutrient deprivation • If nutrient deprivation is brief, a spore is at disadvantage • Fratricidal cannibalism precedes spore formation • In response to nutrient limitation, Spo0A is induced in 1/2 of cells. At this stage, the population is not yet fully committed to spore formation • Spo0A ON --> spore formation, • Spo0A OFF --> no spore formation • Spo0A ON --> produce and secrete toxin that kills and lyses Spo0A OFF cells. • When all the Spo0A cells are lysed and digested, the entire remaining population will form spores • Spo0A ON also make produce membrane-bound immunity protein that neutralizes the lysing toxin • The immunity protein also functions in QS signal transduction • Streptococcus pneumoniae • Peptide QS signal induces competence also causes lysis of sibling cells • Surviving cells may benefit from acquiring DNA, and by the release of host tissue degrading enzymes
Algal Furanones: what can we learn from nature S. Kjelleberg
This is cute, but why exactly are we spending time on QS? What does QS mean to ecology of pathogens? Can we manipulate QS to our advantage? Isn’t it better/easier to just kill the pathogens with antibiotics instead worrying about communication?