Branched‐chain fatty acids: the case for a novel form of cell‐cell signalling during <i>Myxococcus xanthus</i> development

Downward, John; Toal, Douglas R.

doi:10.1111/j.1365-2958.1995.tb02290.x

Cited by 82 publications

(59 citation statements)

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“…The N-acyl homoserine lactones seem to be the most common molecules of this class, but other examples are known. It has been reported that fatty acids are among the set of signal molecules regulating differentiation in Myxococcus xanthus (Downard and Toal, 1995). The plant pathogen Ralstonia (formerly Pseudomonas) solanacearum uses a volatile signal molecule believed to be methyl hydroxypalmitate (Schell, 1996).…”

Section: Discussionmentioning

confidence: 99%

A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule

Barber

Tang²,

Feng³

et al. 1997

Molecular Microbiology

471

512

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SummaryMutations in the seven clustered rpf genes cause downregulated synthesis of extracellular enzymes and reduced virulence of Xanthomonas campestris pathovar campestris (Xcc). The phenotype of mutants in one of the genes, rpfF, can be restored by a diffusible extracellular factor (DSF) produced by all Xcc strains tested, apart from rpfF and rpfB mutants. DSF accumulates in early stationary phase (when synthesis of enzymes is maximal), but levels decline subsequently. Addition of DSF to exponentially-growing wild-type bacteria does not cause precocious enzyme synthesis. rpfB and rpfF are expressed throughout growth, but the rate increases in early stationary phase. RpfB is predicted to be a long-chain fatty acyl CoA ligase, and RpfF shows some relatedness to enoyl CoA hydratases. The properties of DSF suggest that it may be a fatty-acid derivative, and certain lipid preparations possess DSF activity at higher concentrations. These include lipid extracts and acid-hydrolysed lipopolysaccharide and lipid A from Xcc, and purified dodecanoic and hydroxydodecanoic acid. DSF production is confined to certain xanthomonads. We propose a model for the DSF system, which represents a novel mechanism for regulating virulence factor synthesis in response to physiological or environmental changes.

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Section: Discussionmentioning

confidence: 99%

A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule

Barber

Tang²,

Feng³

et al. 1997

Molecular Microbiology

471

512

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“…Unfortunately, the structure of the native E-signal has not been determined. Regardless of its structure, however, extracellular complementation by the endogenous E-signal requires cell-to-cell contact with the wild type (Downard and Toal, 1995;Dworkin, 1996), which contrasts with the volatile activity of 3-OH PAME.…”

Section: Discussionmentioning

confidence: 99%

“…E-signal is believed to be one or more short, branched-chain fatty acids, because the E-signal (esg ) locus appears to encode components of a dehydrogenase complex presumed to be involved in the synthesis of branched-chain fatty acids (Downard and Toal, 1995). In addition, defects in growth, pigmentation and development in esg mutants were corrected by the addition of several different short branched-chain fatty acids (Downard and Toal, 1995). Unfortunately, the structure of the native E-signal has not been determined.…”

Section: Discussionmentioning

confidence: 99%

Identification of 3‐hydroxypalmitic acid methyl ester as a novel autoregulator controlling virulence in Ralstonia solanacearum

Flavier

Clough

Schell

et al. 1997

Molecular Microbiology

282

212

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SummaryExpression of virulence genes in Ralstonia solanacearum, a phytopathogenic bacterium, is controlled by a complex regulatory network that integrates multiple signal inputs. Production of several virulence determinants is co-ordinately reduced by inactivation of phcB, but is restored by growth in the presence of a volatile extracellular factor (VEF) produced by wildtype strains of R. solanacearum. The VEF was purified from spent culture broth by distillation, solvent extraction, and liquid chromatography. Gas chromatography and mass spectroscopy identified 3-hydroxypalmitic acid methyl ester (3-OH PAME) as the major component in the single peak of VEF activity. Authentic 3-OH PAME and the purified VEF were active at Յ1 nM, and had nearly equivalent specific activities for stimulating the expression of eps (the biosynthetic locus for extracellular polysaccharide) in a phcB mutant. Authentic 3-OH PAME also increased the production of three virulence factors by a phcB mutant over 20-fold to wild-type levels, restored normal cell density-associated expression of eps and increased expression of eps when delivered via the vapour phase. Reanalysis of the PhcB amino acid sequence suggested that it is a small-molecule S-adenosylmethionine-dependent methyltransferase, which might catalyse synthesis of 3-OH PAME from a naturally occurring fatty acid. Biologically active concentrations of extracellular 3-OH PAME were detected before the onset of eps expression, suggesting that it is an intercellular signal that autoregulates virulence gene expression in wild-type R. solanacearum. Other than acyl-homoserine lactones, 3-OH PAME is the only endogenous fatty acid derivative shown to be an autoregulator and may be the first example of a new family of compounds that can mediate long-distance intercellular communication.

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“…xanthus development. Fruiting body formation and sporulation in Myxococcus bacteria is another example of controlled death aiding development (25,65,81). "Autocides," which include fatty acids as well as glucosamine, induce autolysis in dense cultures of Myxococcus xanthus and are required for normal fruiting body development and sporulation.…”

Section: Programmed Death In Bacterial Developmentmentioning

confidence: 99%

Programmed Death in Bacteria

Lewis

2000

Microbiol Mol Biol Rev

543

411

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SUMMARY Programmed cell death (PCD) in bacteria plays an important role in developmental processes, such as lysis of the mother cell during sporulation of Bacillus subtilis and lysis of vegetative cells in fruiting body formation of Myxococcus xanthus. The signal transduction pathway leading to autolysis of the mother cell includes the terminal sporulation sigma factor EςK, which induces the synthesis of autolysins CwlC and CwlH. An activator of autolysin in this and other PCD processes is yet to be identified. Autolysis plays a role in genetic exchange in Streptococcus pneumoniae, and the gene for the major autolysin, lytA, is located in the same operon with recA. DNA from lysed cells is picked up by their neighbors and recombined into the chromosome by RecA. LytA requires an unknown activator controlled by a sensory kinase, VncS. Deletion of vncS inhibits autolysis and also decreases killing by unrelated antibiotics. This observation suggests that PCD in bacteria serves to eliminate damaged cells, similar to apoptosis of defective cells in metazoa. The presence of genes affecting survival without changing growth sensitivity to antibiotics (vncS, lytA, hipAB, sulA, and mar) indicates that bacteria are able to control their fate. Elimination of defective cells could limit the spread of a viral infection and donate nutrients to healthy kin cells. An altruistic suicide would be challenged by the appearance of asocial mutants without PCD and by the possibility of maladaptive total suicide in response to a uniformly present lethal factor or nutrient depletion. It is proposed that a low rate of mutation serves to decrease the probability that asocial mutants without PCD will take over the population. It is suggested that PCD is disabled in persistors, rare cells that are resistant to killing, to ensure population survival. It is suggested that lack of nutrients leads to the stringent response that suppresses PCD, producing a state of tolerance to antibiotics, allowing cells to discriminate between nutrient deprivation and unrepairable damage. High levels of persistors are apparently responsible for the extraordinary survival properties of bacterial biofilms, and genes affecting persistence appear to be promising targets for development of drugs aimed at eradicating recalcitrant infections. PCD in unicellular eukaryotes is also considered, including aging in Saccharomyces cerevisiae. Apoptosis-like elimination of defective cells in S. cerevisiae and protozoa suggests that all unicellular life forms evolved altruistic programmed death that serves a variety of useful functions.

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Branched‐chain fatty acids: the case for a novel form of cell‐cell signalling during Myxococcus xanthus development

Cited by 82 publications

References 0 publications

A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule

A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule

Identification of 3‐hydroxypalmitic acid methyl ester as a novel autoregulator controlling virulence in Ralstonia solanacearum

Programmed Death in Bacteria

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