Direct involvement of the CreA transcription factor in penicillin biosynthesis and expression of the pcbAB gene in Penicillium chrysogenum

Cepeda-García, Cristina; Domínguez-Santos, Rebeca; García-Rico, Ramón O.; Garcı́a-Estrada, Carlos; Cajiao, Angela; Fierro, Francisco; Martı́n, Juan F.

doi:10.1007/s00253-014-5760-1

Cited by 52 publications

(39 citation statements)

References 44 publications

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“…No creA knockout strains were identified in analyses of more than 300 transformants. The mutation is probably lethal, as has been reported for F. oxysporum , Penicillium chrysogenum and M. oryzae (Cepeda‐Garcia et al ., ; Fernandez et al ., ; Jonkers and Rep, ).…”

Section: Resultsmentioning

confidence: 99%

Carbon regulation of environmental pH by secreted small molecules that modulate pathogenicity in phytopathogenic fungi

Barad

Ment

et al. 2016

Molecular Plant Pathology

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Fruit pathogens can contribute to the acidification or alkalinization of the host environment. This capability has been used to divide fungal pathogens into acidifying and/or alkalinizing classes. Here, we show that diverse classes of fungal pathogens-Colletotrichum gloeosporioides, Penicillium expansum, Aspergillus nidulans and Fusarium oxysporum-secrete small pH-affecting molecules. These molecules modify the environmental pH, which dictates acidic or alkaline colonizing strategies, and induce the expression of PACC-dependent genes. We show that, in many organisms, acidification is induced under carbon excess, i.e. 175 mm sucrose (the most abundant sugar in fruits). In contrast, alkalinization occurs under conditions of carbon deprivation, i.e. less than 15 mm sucrose. The carbon source is metabolized by glucose oxidase (gox2) to gluconic acid, contributing to medium acidification, whereas catalysed deamination of non-preferred carbon sources, such as the amino acid glutamate, by glutamate dehydrogenase 2 (gdh2), results in the secretion of ammonia. Functional analyses of Δgdh2 mutants showed reduced alkalinization and pathogenicity during growth under carbon deprivation, but not in high-carbon medium or on fruit rich in sugar, whereas analysis of Δgox2 mutants showed reduced acidification and pathogencity under conditions of excess carbon. The induction pattern of gdh2 was negatively correlated with the expression of the zinc finger global carbon catabolite repressor creA. The present results indicate that differential pH modulation by fruit fungal pathogens is a host-dependent mechanism, affected by host sugar content, that modulates environmental pH to enhance fruit colonization.

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Section: Resultsmentioning

confidence: 99%

Carbon regulation of environmental pH by secreted small molecules that modulate pathogenicity in phytopathogenic fungi

Barad

Ment

et al. 2016

Molecular Plant Pathology

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“…For example, in some filamentous fungi, loss of CCR leads to lethality. For example, clean full gene replacements of the CCR transcriptional regulator CreA has not been possible in Fusarium oxysporum [39], Penicillium chrysogenum [40] and Colletotrichum gloeosporoides [41] and results in extremely severe growth defects in Aspergillus nidulans [42, 43]. Consequently, the ability to generate a creA null mutant in A .…”

Section: Resultsmentioning

confidence: 99%

Filamentous fungal carbon catabolite repression supports metabolic plasticity and stress responses essential for disease progression

et al. 2017

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Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A. fumigatus requires a carbon catabolite repression (CCR) mediated genetic network to support in vivo fungal fitness and disease progression. While CCR as mediated by the transcriptional repressor CreA is not required for pulmonary infection establishment, loss of CCR inhibits fungal metabolic plasticity and the ability to thrive in the dynamic infection microenvironment. Our results suggest a model whereby CCR in an environmental filamentous fungus is dispensable for initiation of pulmonary infection but essential for infection maintenance and disease progression. Conceptually, we argue these data provide a foundation for additional studies on fungal factors required to support fungal fitness and disease progression and term such genes and factors, DPFs (disease progression factors).

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“…CreA is a global repressor that ensures the utilization of preferred carbon sources, preventing the expression of genes linked to assimilatory traits of non-preferred carbon sources [109]. CreA is known to negatively influence the production of penicillin at high carbon concentrations and was suggested to act in ochratoxin A regulation [82, 110]; however, it still must be determined how this gene influences Metarhizium spp. secondary metabolism.…”

Section: Discussionmentioning

confidence: 99%

Secondary metabolite gene clusters in the entomopathogen fungus Metarhizium anisopliae: genome identification and patterns of expression in a cuticle infection model

Sbaraini

Guedes²,

Andreis

et al. 2016

BMC Genomics

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BackgroundThe described species from the Metarhizium genus are cosmopolitan fungi that infect arthropod hosts. Interestingly, while some species infect a wide range of hosts (host-generalists), other species infect only a few arthropods (host-specialists). This singular evolutionary trait permits unique comparisons to determine how pathogens and virulence determinants emerge. Among the several virulence determinants that have been described, secondary metabolites (SMs) are suggested to play essential roles during fungal infection. Despite progress in the study of pathogen-host relationships, the majority of genes related to SM production in Metarhizium spp. are uncharacterized, and little is known about their genomic organization, expression and regulation. To better understand how infection conditions may affect SM production in Metarhizium anisopliae, we have performed a deep survey and description of SM biosynthetic gene clusters (BGCs) in M. anisopliae, analyzed RNA-seq data from fungi grown on cattle-tick cuticles, evaluated the differential expression of BGCs, and assessed conservation among the Metarhizium genus. Furthermore, our analysis extended to the construction of a phylogeny for the following three BGCs: a tropolone/citrinin-related compound (MaPKS1), a pseurotin-related compound (MaNRPS-PKS2), and a putative helvolic acid (MaTERP1).ResultsAmong 73 BGCs identified in M. anisopliae, 20 % were up-regulated during initial tick cuticle infection and presumably possess virulence-related roles. These up-regulated BGCs include known clusters, such as destruxin, NG39x and ferricrocin, together with putative helvolic acid and, pseurotin and tropolone/citrinin-related compound clusters as well as uncharacterized clusters. Furthermore, several previously characterized and putative BGCs were silent or down-regulated in initial infection conditions, indicating minor participation over the course of infection.Interestingly, several up-regulated BGCs were not conserved in host-specialist species from the Metarhizium genus, indicating differences in the metabolic strategies employed by generalist and specialist species to overcome and kill their host. These differences in metabolic potential may have been partially shaped by horizontal gene transfer (HGT) events, as our phylogenetic analysis provided evidence that the putative helvolic acid cluster in Metarhizium spp. originated from an HGT event.ConclusionsSeveral unknown BGCs are described, and aspects of their organization, regulation and origin are discussed, providing further support for the impact of SM on the Metarhizium genus lifestyle and infection process.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3067-6) contains supplementary material, which is available to authorized users.

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Direct involvement of the CreA transcription factor in penicillin biosynthesis and expression of the pcbAB gene in Penicillium chrysogenum

Cited by 52 publications

References 44 publications

Carbon regulation of environmental pH by secreted small molecules that modulate pathogenicity in phytopathogenic fungi

Carbon regulation of environmental pH by secreted small molecules that modulate pathogenicity in phytopathogenic fungi

Filamentous fungal carbon catabolite repression supports metabolic plasticity and stress responses essential for disease progression

Secondary metabolite gene clusters in the entomopathogen fungus Metarhizium anisopliae: genome identification and patterns of expression in a cuticle infection model

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