Human Fungal Pathogens of Mucorales and Entomophthorales

Mendoza, Leonel; Vilela, Raquel; Voelz, Kerstin; Ibrahim, Ashraf S.; Voigt, Kerstin; Lee, Soo Chan

doi:10.1101/cshperspect.a019562

Cited by 75 publications

(101 citation statements)

References 208 publications

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“…The virulence potential of this fungus is connected with thermotolerance (5), because other clinically nonrelevant Lichtheimia species possess a lower thermotolerance and stop growth at 42°C (1, 6). So far, missing genomic data has hindered the exploration of further virulence factors (7, 8). Here we present the full genome sequence of L. ramosa , whereas the mitogenome was announced recently (9).…”

Section: Genome Announcementmentioning

confidence: 99%

De Novo Whole-Genome Sequence and Genome Annotation of Lichtheimia ramosa

et al. 2014

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Section: Genome Announcementmentioning

confidence: 99%

De Novo Whole-Genome Sequence and Genome Annotation of Lichtheimia ramosa

et al. 2014

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“…With limited antifungal treatments effective against these invasive infections, there is often a need for surgical debridement or amputation (Spellberg et al 2016). In disseminated cases, mucormycosis may present with a mortality rate of over 90% (Mendoza et al 2014). Reports of chronic mucormycosis have also emerged, affecting both immunocompromised and immunocompetent patients (Alan et al 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Studies frequently focus upon the interaction of a single species of the Mucorales order with innate immune cells (Warris et al 2005; Chamilos et al 2008; Schmidt et al 2013; Kraibooj et al 2014; Inglesfield et al 2018). However, between Mucorales species, and across infecting isolates, numerous phenotypic and genomic differences can be observed (Hoffmann et al 2013; Mendoza et al 2014; Schwartze et al 2014). Whether each species within this family employs the same mechanism to cause infection remains unclear, however the range of virulence profiles displayed across the family indicates there may be diversified mechanisms at work (Petraitis et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Bacterial endosymbionts influence fungal transcriptional profiles with implications for host response in the human fungal pathogensRhizopus microsporusandRhizopus delemar

Sephton-Clark

Itabangi

et al. 2019

Preprint

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Mucorales spores, the causative agents of mucormycosis, interact with the innate immune system to cause acute, chronic, or resolving infection. Understanding the factors that influence disease initiation and progression is key to understanding mucormycosis and developing new treatments. Complicating this, mucormycosis can be caused by a number of species that span the Mucorales genus and may be host to bacterial endosymbionts. This study sets out to examine the differences between two species in the Mucorales order by characterising their differential interactions with the innate immune system, and their interactions with environmental bacterial endosymbionts. Through a holistic approach, this study examines the transcriptional responses ofRhizopus delemarandRhizopus microsporus,two of the most commonly diagnosed species, to innate immune cells. This study also examines the immune cell response and assesses the variation in these responses, given the presence or absence of bacterial endosymbionts within the fungi. We see that the fungal response is driven by interaction with innate immune cells. The effect of the bacterial endosymbiont on the fungus is species specific, with a minimal in the absence of stress, but strongly influencing fungal transcripts during interaction with innate immune cells. In contrast, we observe that the macrophage response varies depending on the infecting fungal species, but also depending on endosymbiont status. The most successful macrophages elicit a pro-inflammatory response, and we see that through germination inhibition macrophage survival is enhanced. This work reveals species-specific host responses to related Mucorales spores and shows that bacterial endosymbionts impact the innate immune cell response.

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“…We conducted microsynteny analysis to infer which RP gene pairs were generated by the WGDs in the pin molds. The estimated divergence time between Phycomyces and Rhizopus is over 750 mya (Mendoza, et al 2014). Most, if not all, microsynteny blocks generated by the first WGD might have lost during the evolution of these pin molds.…”

Section: Resultsmentioning

confidence: 99%

Parallel Concerted Evolution of Ribosomal Protein Genes in Fungi and Its Adaptive Significance

Mullis¹,

Lü²,

Ye³

et al. 2019

Preprint

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9Ribosomal proteins (RPs) genes encode structure components of ribosomes, the cellular 2 0 machinery for protein synthesis. A single functional copy has been maintained in most of 78-80 2 1 RP families in animals due to evolutionary constraints imposed by gene dosage balance. Some 2 2 fungal species have maintained duplicate copies in most RP families. How the RP genes were 2 3 duplicated and maintained in these fungal species, and their functional significance remains 2 4 unresolved. To address these questions, we identified all RP genes from 295 fungi and inferred 2 5 the timing and nature of gene duplication for all RP families. We found that massive duplications 2 6 of RP genes have independently occurred by different mechanisms in three distantly related 2 7 lineages. The RP duplicates in two of them, budding yeast and Mucoromycota, were mainly 2 8 created by whole genome duplication (WGD) events. However, in fission yeasts, duplicate RP 2 9 genes were likely generated by retroposition, which is unexpected considering their dosage 3 0 sensitivity. The sequences of most RP paralogs in each species have been homogenized by 3 1 repeated gene conversion, demonstrating parallel concerted evolution, which might have 3 2 facilitated the retention of their duplicates. Transcriptomic data suggest that the duplication and 3 3 retention of RP genes increased RP transcription abundance. Physiological data indicate that 3 4increased ribosome biogenesis allowed these organisms to rapidly consuming sugars through 3 5 fermentation while maintaining high growth rates, providing selective advantages to these 3 6 species in sugar-rich environments.

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Human Fungal Pathogens of Mucorales and Entomophthorales

Cited by 75 publications

References 208 publications

De Novo Whole-Genome Sequence and Genome Annotation of Lichtheimia ramosa

De Novo Whole-Genome Sequence and Genome Annotation of Lichtheimia ramosa

Bacterial endosymbionts influence fungal transcriptional profiles with implications for host response in the human fungal pathogensRhizopus microsporusandRhizopus delemar

Parallel Concerted Evolution of Ribosomal Protein Genes in Fungi and Its Adaptive Significance

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