Melanin, Radiation, and Energy Transduction in Fungi.
Casadevall Arturo,Cordero Radames J B,Bryan Ruth,Nosanchuk Joshua,Dadachova Ekaterina
Microbiology spectrum
Melanin pigments are found in many diverse fungal species, where they serve a variety of functions that promote fitness and cell survival. Melanotic fungi inhabit some of the most extreme habitats on earth such as the damaged nuclear reactor at Chernobyl and the highlands of Antarctica, both of which are high-radiation environments. Melanotic fungi migrate toward radioactive sources, which appear to enhance their growth. This phenomenon, combined with the known capacities of melanin to absorb a broad spectrum of electromagnetic radiation and transduce this radiation into other forms of energy, raises the possibility that melanin also functions in harvesting such energy for biological usage. The ability of melanotic fungi to harness electromagnetic radiation for physiological processes has enormous implications for biological energy flows in the biosphere and for exobiology, since it provides new mechanisms for survival in extraterrestrial conditions. Whereas some features of the way melanin-related energy transduction works can be discerned by linking various observations and circumstantial data, the mechanistic details remain to be discovered.
10.1128/microbiolspec.FUNK-0037-2016
4-Hydroxyphenylpyruvate Dioxygenase Thermolability Is Responsible for Temperature-Dependent Melanogenesis in Aeromonas salmonicida subsp. .
Qiao Yunqian,Wang Jiao,Wang He,Chai Baozhong,Rao Chufeng,Chen Xiangdong,Du Shishen
Applied and environmental microbiology
subsp. is a major pathogen affecting fisheries worldwide and is a well-known pigmented member of the genus. This subspecies produces melanin at ≤22°C. However, melanogenesis decreases as the culture temperature increases and is completely suppressed at 30°C to 35°C, while bacterial growth is unaffected. The mechanism and biological significance of this temperature-dependent melanogenesis remain unclear. Heterologous expression of an subsp. 4-hydroxyphenylpyruvate dioxygenase (HppD), the most critical enzyme in the homogentisic acid (HGA)-melanin synthesis pathway, results in thermosensitive pigmentation in , suggesting that HppD plays a key role in this process. In this study, we demonstrated that the thermolability of HppD is responsible for the temperature-dependent melanization of subsp. Substitutions of three residues, S18T, P103Q, and L119P, in subsp. HppD increased the thermostability of this enzyme and resulted in temperature-independent melanogenesis. Moreover, the replacement of the corresponding residues in HppD from strain WS, which forms pigment independent of temperature, with those of subsp. HppD resulted in thermosensitive melanogenesis. A structural analysis suggested that mutations at these sites, especially at position P103, strengthen the secondary structure of HppD and greatly improve its thermal stability. Additionally, we found that the HppD sequences of all subsp. isolates were identical and that two of the three residues were clearly distinct from those of other strains. subsp. s is the causative agent of furunculosis, a bacterial septicemia of cold-water fish of the family. Although other species can produce melanin, subsp. is the only member of this genus that has been reported to exhibit temperature-dependent melanization. Here, we demonstrated that thermosensitive melanogenesis in subsp. strains is due to the thermolability of 4-hydroxyphenylpyruvate dioxygenase (HppD). Additionally, we confirmed that this thermolabile HppD exhibited higher activity at low temperatures than its mesophilic homologues, suggesting this as an adaptive strategy of this enzyme to the psychrophilic lifestyle of subsp. The strictly conserved sequences among subsp. isolates and the specific possession of P103 and L119 residues could be used as a reference for the identification of subsp. isolates.
10.1128/AEM.01926-18
Melanin and pyomelanin in Aspergillus fumigatus: from its genetics to host interaction.
Perez-Cuesta U,Aparicio-Fernandez L,Guruceaga X,Martin-Souto L,Abad-Diaz-de-Cerio A,Antoran A,Buldain I,Hernando F L,Ramirez-Garcia A,Rementeria A
International microbiology : the official journal of the Spanish Society for Microbiology
Aspergillus fumigatus is a worldwide-distributed saprophytic fungus and the major cause of invasive aspergillosis. This fungus can produce two types of melanin-dihydroxynaphthalene melanin (DHN-melanin) and pyomelanin. These pigments are considered important resistance mechanisms to stress, as well as virulence factors. The aim of this review is to present the current knowledge of the genetic basis and metabolic pathways of melanin production, their activation, function, and interaction with the host immune system. The DHN-melanin pathway is encoded in a cluster that includes six genes (abr1, abr2, ayg1, arp1, arp2, and pksP/alb1 genes) whose encoded proteins seem to be the origin of the pigment in endosomes. These vesicles are secreted and the pigment is subsequently located in the wall of the conidium beneath the rodlet layer. Unlike DHN-melanin, pyomelanin does not have its own biosynthetic pathway but is related to the activation of the L-tyrosine/L-phenylalanine degradation pathway that includes a cluster of six genes (hppD, hmgX, hmgA, fahA, maiA, and hmgR). Its production is due to the polymerization of homogentisic acid and is linked to conidial germination. Despite the knowledge gained in recent years, further studies will be necessary to confirm the pathways that produce these pigments and their role in the virulence mechanisms of A. fumigatus.
10.1007/s10123-019-00078-0
Laccase Gene Sh-lac Is Involved in the Growth and Melanin Biosynthesis of Scleromitrula shiraiana.
Lǚ Zhiyuan,Kang Xin,Xiang Zhonghuai,He Ningjia
Phytopathology
Scleromitrula shiraiana causes the popcorn disease in mulberry trees resulting in severe economic losses. Previous studies have shown that melanin may play a vital role in establishing the pathogenicity of fungi. In the present study, we identified the melanin produced in S. shiraiana belongs to DHN melanin by gas chromatography-mass spectrometry, and cloned the laccase Sh-lac, a potential DHN melanin biosynthesis gene from S. shiraiana. We obtained two stable Sh-lac silenced transformants using RNAi, ilac-4 and 8 to elucidate the DHN melanin biosynthetic pathway in S. shiraiana. The melanin production of ilac-4 and ilac-8 was significantly reduced, and their vegetative growth was also suppressed. Results such as these led to a proposal that Sh-lac played a key role in DHN melanin formation in S. shiraiana and may function differentially with other melanin biosynthetic genes. The inhibition of melanin was accompanied by the decrease of oxalic acid and the adhesion of hyphae was impaired. Our results indicated that laccase was an important enzyme in the synthesis of melanin and might play a critical role in the pathogenicity of S. shiraiana.
10.1094/PHYTO-04-16-0180-R
Calcium sequestration by fungal melanin inhibits calcium-calmodulin signalling to prevent LC3-associated phagocytosis.
Kyrmizi Irene,Ferreira Helena,Carvalho Agostinho,Figueroa Julio Alberto Landero,Zarmpas Pavlos,Cunha Cristina,Akoumianaki Tonia,Stylianou Kostas,Deepe George S,Samonis George,Lacerda João F,Campos António,Kontoyiannis Dimitrios P,Mihalopoulos Nikolaos,Kwon-Chung Kyung J,El-Benna Jamel,Valsecchi Isabel,Beauvais Anne,Brakhage Axel A,Neves Nuno M,Latge Jean-Paul,Chamilos Georgios
Nature microbiology
LC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway regulated by Rubicon, with an emerging role in immune homeostasis and antifungal host defence. Aspergillus cell wall melanin protects conidia (spores) from killing by phagocytes and promotes pathogenicity through blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent activation of LAP. However, the signalling regulating LAP upstream of Rubicon and the mechanism of melanin-induced inhibition of this pathway remain incompletely understood. Herein, we identify a Ca signalling pathway that depends on intracellular Ca sources from endoplasmic reticulum, endoplasmic reticulum-phagosome communication, Ca release from phagosome lumen and calmodulin (CaM) recruitment, as a master regulator of Rubicon, the phagocyte NADPH oxidase NOX2 and other molecular components of LAP. Furthermore, we provide genetic evidence for the physiological importance of Ca-CaM signalling in aspergillosis. Finally, we demonstrate that Ca sequestration by Aspergillus melanin inside the phagosome abrogates activation of Ca-CaM signalling to inhibit LAP. These findings reveal the important role of Ca-CaM signalling in antifungal immunity and identify an immunological function of Ca binding by melanin pigments with broad physiological implications beyond fungal disease pathogenesis.
10.1038/s41564-018-0167-x
Aspergillus Cell Wall Melanin Blocks LC3-Associated Phagocytosis to Promote Pathogenicity.
Akoumianaki Tonia,Kyrmizi Irene,Valsecchi Isabel,Gresnigt Mark S,Samonis George,Drakos Elias,Boumpas Dimitrios,Muszkieta Laetitia,Prevost Marie-Christine,Kontoyiannis Dimitrios P,Chavakis Triantafyllos,Netea Mihai G,van de Veerdonk Frank L,Brakhage Axel A,El-Benna Jamel,Beauvais Anne,Latge Jean-Paul,Chamilos Georgios
Cell host & microbe
Concealing pathogen-associated molecular patterns (PAMPs) is a principal strategy used by fungi to avoid immune recognition. Surface exposure of PAMPs during germination can leave the pathogen vulnerable. Accordingly, β-glucan surface exposure during Aspergillus fumigatus germination activates an Atg5-dependent autophagy pathway termed LC3-associated phagocytosis (LAP), which promotes fungal killing. We found that LAP activation also requires the genetic, biochemical or biological (germination) removal of A. fumigatus cell wall melanin. The attenuated virulence of melanin-deficient A. fumigatus is restored in Atg5-deficient macrophages and in mice upon conditional inactivation of Atg5 in hematopoietic cells. Mechanistically, Aspergillus melanin inhibits NADPH oxidase-dependent activation of LAP by excluding the p22phox subunit from the phagosome. Thus, two events that occur concomitantly during germination of airborne fungi, surface exposure of PAMPs and melanin removal, are necessary for LAP activation and fungal killing. LAP blockade is a general property of melanin pigments, a finding with broad physiological implications.
10.1016/j.chom.2015.12.002
Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism in fungal disease.
Chamilos Georgios,Akoumianaki Tonia,Kyrmizi Irene,Brakhage Axel,Beauvais Anne,Latge Jean-Paul
Autophagy
Intracellular swelling of conidia of the major human airborne fungal pathogen Aspergillus fumigatus results in surface exposure of immunostimulatory pathogen-associated molecular patterns (PAMPs) and triggers activation of a specialized autophagy pathway called LC3-associated phagocytosis (LAP) to promote fungal killing. We have recently discovered that, apart from PAMPs exposure, cell wall melanin removal during germination of A. fumigatus is a prerequisite for activation of LAP. Importantly, melanin promotes fungal pathogenicity via targeting LAP, as a melanin-deficient A. fumigatus mutant restores its virulence upon conditional inactivation of Atg5 in hematopoietic cells of mice. Mechanistically, fungal cell wall melanin selectively excludes the CYBA/p22phox subunit of NADPH oxidase from the phagosome to inhibit LAP, without interfering with signaling regulating cytokine responses. Notably, inhibition of LAP is a general property of melanin pigments, a finding with broad physiological implications.
10.1080/15548627.2016.1157242