Lipid Signaling in Pathogenic Fungi

Rhome, Ryan; Poeta, Maurizio Del

doi:10.1146/annurev.micro.091208.073431

Cited by 36 publications

(28 citation statements)

References 70 publications

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“…In general, glycosylated Cers are important signaling molecules in multicellular organisms ( 49 ), but no specifi c functions for PI-Cers are known in lower eukaryotes, except that inhibition of AUR1 is lethal to S. cerevisiae ( 50 ) and that PI-Cer is at least indirectly associated with the pathogenicity of Cryptococcus neoformans ( 51 ). A possible signaling function of PI-Cers in myxobacterial fruiting body formation or sporulation remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive insight into the lipid composition of Myxococcus xanthus by UPLC-ESI-MS

Lorenzen

Bozhüyük

Cortina

et al. 2014

Journal of Lipid Research

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This article is available online at http://www.jlr.org that allows researchers to investigate the lipid repertoire of these bacteria as a whole, in order to unveil alterations in the lipid composition on the molecular level as a function of different metabolic conditions or growth stages.In recent years, progress has been made in elucidating the biosynthesis and putative biological importance of myxobacterial FAs including branched-chain ( 6 ), straightchain ( 7 ), unsaturated ( 8 ), and hydroxylated FAs, as well as sphingoid species ( 9 ), particularly with regard to the best studied myxobacterial model organism Myxococcus xanthus . In these studies, methanolysis-derived FA methyl esters (FAMEs) or selected lipid classes were analyzed by means of GC-MS; there is thus only limited information about the complete lipidome of M. xanthus . High temperature GC-MS was applied to unhydrolyzed lipid extracts in order to elucidate the structures and relative abundance of neutral lipids ( 10 ) and unusual iso-branched alkyldiacylglycerols ( 4 ), molecules that exhibit signaling functions in this organism ( 5 ). HPLC ESI-MS/MS experiments were used to determine changes in the glycerophosphoethanolamine (PE) composition of mutant strains with inactivated acyltransferases ( 11 ) on the one hand, and to determine the ratio of certain ether PEs to acyl PEs during the process of starvation-induced fruiting body formation ( 4 ) on the other hand. In a recent publication on the myxobacterial ether lipid biosynthesis and the importance of these lipids for the myxobacterial life cycle ( 12 ), all these methods had to be combined in order to examine the effects of gene inactivations on the lipid composition of the respective mutants, as the occurrence and abundance of Myxobacteria are a globally occurring order of soildwelling Gram-negative ␦ -proteobacteria that attracts interest due to a wide range of remarkable features including cooperative motility, predation, simple multicellularity [including fungi-like fruiting body formation ( 1 )], and as producers of a wide range of secondary metabolites ( 2 ). Additionally, they exhibit a complex pattern of primary metabolites, with fatty acyl species and associated lipids the most well-studied. Some of these lipids are involved in processes like chemotaxis or starvation-induced fruiting body formation, either as biomarkers or chemotactic signals ( 3-5 ). However, to date, no methodology has been described This work was supported in part by the Emmy Noether program of the Deutsche Forschungsgemeinschaft (DFG).

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Section: Discussionmentioning

confidence: 99%

A comprehensive insight into the lipid composition of Myxococcus xanthus by UPLC-ESI-MS

Lorenzen

Bozhüyük

Cortina

et al. 2014

Journal of Lipid Research

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“…Lipids are involved in fungal development and pathogenicity (39,100,114,127). In C. albicans, lipid molecules such as fatty acids and eicosanoids have been reported to modulate the Y-H transition.…”

Section: Fatty Acids Eicosanoids and Cyclooxygenase Inhibitorsmentioning

confidence: 99%

Modulation of Morphogenesis in Candida albicans by Various Small Molecules

2011

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The pathogenic yeast Candida albicans, a member of the mucosal microbiota, is responsible for a large spectrum of infections, ranging from benign thrush and vulvovaginitis in both healthy and immunocompromised individuals to severe, life-threatening infections in immunocompromised patients. A striking feature of C. albicans is its ability to grow as budding yeast and as filamentous forms, including hyphae and pseudohyphae. The yeast-to-hypha transition contributes to the overall virulence of C. albicans and may even constitute a target for the development of antifungal drugs. Indeed, impairing morphogenesis in C. albicans has been shown to be a means to treat candidiasis. Additionally, a large number of small molecules such as farnesol, fatty acids, rapamycin, geldanamycin, histone deacetylase inhibitors, and cell cycle inhibitors have been reported to modulate the yeast-to-hypha transition in C. albicans. In this minireview, we take a look at molecules that modulate morphogenesis in this pathogenic yeast. When possible, we address experimental findings regarding their mechanisms of action and their therapeutic potential. We discuss whether or not modulating morphogenesis constitutes a strategy to treat Candida infections.

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“…These signaling events are stimulated by cell growth, differentiation, and external stimuli, among other signaling factors. Signaling events involved in laccase regulation include those in response to changing levels of glucose, nitrogen, oxygen, and the metal cofactors iron and copper; they also include the adenyl cyclase pathway (cyclic AMP and downstream targets), the MAPK STE12 and high osmolarity glycerol (HOG1) pathways, and sphingolipid production [34,[66][67][68][69][70][71][72].…”

Section: Regulation/signal Transductionmentioning

confidence: 99%

“…Sphingolipid production is an important pathway for maintaining cell membrane integrity, which is critical both for growth of the fungus in vitro and for the expression and cell wall localization of laccase [20,72]. Inositolphosphoryl ceramide synthase (IPC1) is a fungal enzyme that can regulate diacylglycerol (DAG) production.…”

Section: Regulation/signal Transductionmentioning

confidence: 99%

“…Thus, the transition to becoming a pathogen could be a simple alteration in protein regulation or localization that confers virulence when exposed to the appropriate microenvironment in the host [20,67,68,72,95]. Based on these principles, understanding molecular events involved in virulence expression may allow us to anticipate genomic changes that alter virulence of the organism in the saprophytic fungal community that provides a reservoir of infection.…”

Section: Future Perspectivesmentioning

confidence: 99%

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Lessons from Cryptococcal Laccase: From Environmental Saprophyte to Pathogen

Chen

Williamson

2011

Curr Fungal Infect Rep

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Cryptococcus is an opportunistic pathogen that lives in the environment as a free-living yeast and inflicts disease in humans, primarily in immunocompromised patients such as organ-transplant recipients and people with HIV/AIDS. A key factor allowing emergence of this fungal pathogen is a copper-containing laccase enzyme that facilitates nutrient foraging as a saprophyte and offers protection against environmental dangers such as freeliving amoebae and mammalian macrophages during infection. The promiscuous substrate specificity of laccase facilitates the degradation of hard plant lignin polymers as well as the synthesis of lignin-like pigments from plant flavonoids and melanin pigments from dopamine. The enzyme also possesses an iron oxidase activity that prevents Fenton product formation in macrophages and another activity that allows synthesis of immune-modulatory prostaglandins that fool the host, shutting off an effective immune response. This review provides a brief overview of key points in laccase function and its role in virulence, as well as regulation and trafficking of the enzyme during the interconversion between saprophyte and pathogen, yielding insights into pathogenesis from this adaptable pathogen.

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Lipid Signaling in Pathogenic Fungi

Cited by 36 publications

References 70 publications

A comprehensive insight into the lipid composition of Myxococcus xanthus by UPLC-ESI-MS

A comprehensive insight into the lipid composition of Myxococcus xanthus by UPLC-ESI-MS

Modulation of Morphogenesis in Candida albicans by Various Small Molecules

Lessons from Cryptococcal Laccase: From Environmental Saprophyte to Pathogen

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