An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

Chibucos, Marcus C.; Soliman, Sameh S. M.; Gebremariam, Teclegiorgis; Lee, Hong-Kyu; Daugherty, Sean C.; Orvis, Joshua; Shetty, Amol C.; Crabtree, Jonathan; Hazen, Tracy H.; Etienne, Kizee A.; Kumari, Priti; O’Connor, Timothy G.; Rasko, David A.; Filler, Scott G.; Fraser, Claire M.; Lockhart, Shawn R.; Skory, Christopher D.; Ibrahim, Ashraf S.; Bruno, Vincent M.

doi:10.1038/ncomms12218

Cited by 112 publications

(135 citation statements)

References 76 publications

Supporting

Mentioning

129

Contrasting

Order By: Relevance

“…Interestingly, isolates of Entomopthorales, which were previously taxonomically considered close to Mucorales but do not cause invasive disease, lack the presence of CotH [17]. Collectively, these data point to the unique interaction between Mucorales CotH and endothelial cell GRP78 receptor and to the ability of CotH to mediate invasive disease.…”

Section: Mucorales Invade the Endothelium Through Unique Receptorsmentioning

confidence: 92%

Molecular mechanisms of mucormycosis—The bitter and the sweet

2017

Self Cite

View full text Add to dashboard Cite

Section: Mucorales Invade the Endothelium Through Unique Receptorsmentioning

confidence: 92%

Molecular mechanisms of mucormycosis—The bitter and the sweet

2017

Self Cite

View full text Add to dashboard Cite

“…The risk for intubation should be assessed carefully as it is associated with higher mortality. The introduction of non-invasive tests, notably those based on next-generation sequencing (NGS), transcriptomics, and proteomics, may reduce the need for FOB/BAL [12][13][14][15][16]. Updated research is needed,…”

Section: General Considerationsmentioning

confidence: 99%

Diagnosis of severe respiratory infections in immunocompromised patients

et al. 2020

View full text Add to dashboard Cite

An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (Aspergillus, Mucorales, and Pneumocystis jirovecii) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.

show abstract

“…For example, it has been shown that pathogenicity of these species is linked to the variable copy number of the gene encoding CotH, a family of cell surface proteins important for the spores’ interactions with and adherence to endothelial cells. Iron-scavenging and melanisation pathways have also been shown to play a role in pathogenicity (Chibucos et al 2016, Andrianaki et al 2018). In addition to fungal genome plasticity and transcriptional responses to host stimuli, fungal-host interactions can be further modulated by bacterial endosymbionts (Itabangi et al, 2019; Partida-Martinez & Hertweck 2005).…”

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

View full text Add to dashboard Cite

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.

show abstract

An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

Cited by 112 publications

References 76 publications

Molecular mechanisms of mucormycosis—The bitter and the sweet

Molecular mechanisms of mucormycosis—The bitter and the sweet

Diagnosis of severe respiratory infections in immunocompromised patients

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

Contact Info

Product

Resources

About