Comparative genome-wide analysis of extracellular small RNAs from the mucormycosis pathogen Rhizopus delemar

Liu, Muxing; Bruni, Gillian O.; Taylor, Christopher M.; Wang, Ping

doi:10.1038/s41598-018-23611-z

Cited by 40 publications

(28 citation statements)

References 33 publications

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“…These molecules can contain a variety of molecules, including small RNAs (Peres da Silva et al, 2015). Transcriptomic analysis on EVs from two clinical strains of R. delemar showed an abundance of extracellular small RNAs (exRNAs) that varied in types and length (Liu et al, 2018). Prediction programs for miRNA suggested that the majority of secreted miRNA targeted host genes, specifically those related to carbohydrate metabolism, secondary metabolite biosynthesis, and the two-component system.…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

Understanding Mucormycoses in the Age of “omics”

2020

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Mucormycoses are deadly invasive infections caused by several fungal species belonging to the subphylum Mucoromycotina, order Mucorales. Hallmarks of disease progression include angioinvasion and tissue necrosis that aid in fungal dissemination through the blood stream, causing deeper infections and resulting in poor penetration of antifungal agents to the site of infection. In the absence of surgical removal of the infected focus, antifungal therapy alone is rarely curative. Even when surgical debridement is combined with high-dose antifungal therapy, the mortality associated with mucormycoses is >50%. The unacceptably high mortality rate, limited options for therapy and the extreme morbidity of highly disfiguring surgical therapy provide a clear mandate to understand the molecular mechanisms that govern pathogenesis with the hopes of developing alternative strategies to treat and prevent mucormycoses. In the absence of robust forward and reverse genetic systems available for this taxonomic group of fungi, unbiased next generation sequence (NGS)-based approaches have provided much needed insights into our understanding of many aspects of Mucormycoses, including genome structure, drug resistance, diagnostic development, and fungus-host interactions. Here, we will discuss the specific contributions that NGSbased approaches have made to the field and discuss open questions that can be addressed using similar approaches.

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Section: Extracellular Vesiclesmentioning

confidence: 99%

Understanding Mucormycoses in the Age of “omics”

2020

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“…While disease can be caused by several species in the Mucorales order, Rhizopus delemar and Rhizopus microsporus are responsible for the majority of infections (Liu et al 2018). Risk factors for developing the disease include, but are not limited to: innate immune cell deficiencies, uncontrolled diabetes, immune suppression, skin barrier breaches and iron overload (Baldin & Ibrahim 2017).…”

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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“…Current antifungal treatments are ineffective, resulting in the reliance upon surgical debridement of infected tissues ( 30 ), often leading to long-term disability. Disease can be caused by several species of the Mucorales order; however, Rhizopus delemar , previously known as Rhizopus oryzae , accounts for 70% of cases ( 31 ). Spores are the infectious agents of mucormycosis.…”

Section: Introductionmentioning

confidence: 99%

Pathways of Pathogenicity: Transcriptional Stages of Germination in the Fatal Fungal Pathogen Rhizopus delemar

Sephton-Clark

Muñoz

Ballou

et al. 2018

mSphere

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Germination is key to the growth of many organisms, including fungal spores. Mucormycete spores exist abundantly within the environment and germinate to form hyphae. These spores are capable of infecting immunocompromised individuals, causing the disease mucormycosis. Germination from spore to hyphae within patients leads to angioinvasion, tissue necrosis, and often fatal infections. This study advances our understanding of how spore germination occurs in the mucormycetes, identifying processes we may be able to inhibit to help prevent or treat mucormycosis.

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Comparative genome-wide analysis of extracellular small RNAs from the mucormycosis pathogen Rhizopus delemar

Cited by 40 publications

References 33 publications

Understanding Mucormycoses in the Age of “omics”

Understanding Mucormycoses in the Age of “omics”

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

Pathways of Pathogenicity: Transcriptional Stages of Germination in the Fatal Fungal Pathogen Rhizopus delemar

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