Molecular mechanisms of mucormycosis—The bitter and the sweet

Baldin, Clara; Ibrahim, Ashraf S.

doi:10.1371/journal.ppat.1006408

Cited by 180 publications

(206 citation statements)

References 46 publications

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“…Mucorales, which are thermotolerant fungi, can be found in decaying organic material [28]. These fungi can cause Mucormycosis disease which is considered as the third common invasive fungal infection in patients who undergo organ transplantations or having hematologic malignant tumors [29]. Although there are treatment options for mucormycosis, this disease is characterized by high mortality rates often higher than 40% and in some cases can reach 100% [30,31].…”

Section: Grp78 and Fungal Infectionmentioning

confidence: 99%

GRP78: A cell's response to stress

2019

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Section: Grp78 and Fungal Infectionmentioning

confidence: 99%

GRP78: A cell's response to stress

2019

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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). With limited antifungal treatments effective against these invasive infections, there is often a need for surgical debridement or amputation (Spellberg et al 2016).…”

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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“…During Mucorales infection, swollen spores form germlings, which adhere to and penetrate endothelial cells, rapidly invade blood vessels, and disseminate, causing necrosis 34-37 . Treatment requires debridement or amputation in combination with antifungal therapy and mortality rates approach 100% in disseminated cases 21,38 .…”

Section: Introductionmentioning

confidence: 99%

Environmental interactions with amoebae as drivers of bacterial-fungal endosymbiosis and pathogenicity

Itabangi

Pcs

Zhou

et al. 2019

Preprint

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Environmentally ubiquitous fungal spores of the Mucorales order cause acute invasive infections through germination and evasion of the mammalian host immune system. Early phagocyte control of spore germination plays a key role in controlling infection, yet swelling Mucorales spores evade phagocytosis through an unknown mechanism. Here we investigate fungal immune evasion in a clinical isolate of Rhizopus microsporus and reveal the role of a bacterial endosymbiont, Ralsonia pickettii, in fungal pathogenesis. Analysis of phagocytosis rates in wild type and cured fungal isolates demonstrates a role for the endosymbiont in immune cell evasion through disruption of the cytoskeleton and phagosome maturation. Further analysis of bacterial secreted products revealed the presence of a previously uncharacterized secondary metabolite whose production is induced by the presence of the fungus. Analysis of the bacterial genome and condition-dependent RNAseq implicate a cryptic type I polyketide synthase. Subsequent analysis of wild type and cured spores in a zebrafish larvae model of infection demonstrate a role for the endosymbiont in suppressing macrophage and neutrophil recruitment to the site of infection. Finally, we demonstrate that this has implications for fungal clearance in an immunocompetent murine model of infection. Together, these findings identify for the first time a role for a bacterial endosymbiont in the pathogenesis of Rhizopus microsporus during animal infection.

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Molecular mechanisms of mucormycosis—The bitter and the sweet

Cited by 180 publications

References 46 publications

GRP78: A cell's response to stress

GRP78: A cell's response to stress

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

Environmental interactions with amoebae as drivers of bacterial-fungal endosymbiosis and pathogenicity

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