High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis

Zhai, Bing; Ola, Mihaela; Rolling, Thierry; Tosini, Nicholas L.; Joshowitz, Sari; Littmann, Eric R.; Amoretti, Luigi A.; Fontana, Emily; Wright, Roberta J.; Miranda, Edwin; Veelken, Charlotte A; Morjaria, Sejal; Peled, Jonathan U.; Brink, Marcel R.M. van den; Babady, N. Esther; Butler, Geraldine; Taur, Ying; Hohl, Tobias M.

doi:10.1038/s41591-019-0709-7

Cited by 202 publications

(185 citation statements)

References 54 publications

(65 reference statements)

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“…In our patient's disease phase upon his admission to the hospital, COVID-19 together with diabetes might have created a milieu that allowed microorganisms (e.g., C. glabrata, the last in the temporal sequence), including those resistant to antimicrobial agents, to thrive (likely in the gastrointestinal tract) and, hence, reach the bloodstream [32,33]. Immunosuppression and mucosal barrier disruption are, among others, well-recognized factors for isolation of C. glabrata from patient blood cultures [34] and, to some extent, bloodstream isolates are in vitro resistant to echinocandins [16,25,35].…”

Section: Discussionmentioning

confidence: 99%

Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report

Posteraro

Torelli

Vella

et al. 2020

JoF

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Coinfections with bacteria or fungi may be a frequent complication of COVID-19, but coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly due to multidrug-resistant Gram-negative bacteria, and lastly due to a possibly fatal Candida glabrata. The development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report

Posteraro

Torelli

Vella

et al. 2020

JoF

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“…Although the impact of the microbiome in health and disease has been established, concurrent analysis of the bacterial/fungal consortium and its balance have been understudied [61]. This knowledge gap may be in part due to technical limitations within the metagenomic field; however, one can imagine that there is a vast number of cross-kingdom interactions that are important in the human host.…”

Section: Discussionmentioning

confidence: 99%

The gut mycobiome: The overlooked constituent of clinical outcomes and treatment complications in patients with cancer and other immunosuppressive conditions

Galloway-Peña

Kontoyiannis

2020

PLoS Pathog

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Extensive efforts have focused on investigating the contributions of the intestinal microbiome to health and disease, including immunomodulation [1, 2]. While the term "microbiome" technically refers to microorganisms including bacteria, fungi, viruses, protozoa, and parasites, the majority of studies focus on the bacteriome [3]. Although the bacteriome constitutes >99% of the microbiome [4] (which is potentially the reason most studies focus on the bacteriome), it is irrefutable that the commensal fungi, or the "mycobiome," alongside the other microorganisms, coexist and interact ways that can be beneficial or detrimental to the host [5-7]. Emerging research has focused on how the bacteriome relates to gastrointestinal (GI) disorders, cancer therapy-related toxicities, and stem-cell transplantation outcomes; including correlations with infection, graft-versus-host disease (GvHD), tumorigenesis, cancer relapse, and mortality [8-11]. Thus far, there has been a lack of dedicated research focusing on the influence of mycobiome-associated immunomodulation in patients with cancer and other states of immunosuppression. Herein, by focusing on the gut ecosystem, we discuss the role of fungi in various patient populations, the importance of bacterial-fungal dysbiosis, and offer ideas for future investigations regarding the role of mycobiome. Current implications of gut fungi in patients with cancer or critical illness Fungal diversity and density are low in healthy subjects [7], although the factors for colonization resistance against fungi in the gut are inadequately understood. It has been long known that commensal bacteria limit fungal colonization via activation of mucosal innate immunity by bacterial derived metabolites [12], while antibacterial agents can predispose individuals to Candida albicans colonization and infections [13]. For example, antibiotic-induced dysbiosis of intestinal microbes, such as Bacteriodes spp., was linked to a reduction in the cathelicidin antimicrobial peptide (CRAMP), which resulted in the outgrowth of intestinal Candida spp. [12]. Recently, it was found that an antibiotic-induced reduction in the levels of bacterial derived short-chain fatty acids (SCFAs) in the cecum enhanced GI colonization of C. albicans [14]. Antibiotics, however, are not the only factor that can potentially result in increased fungal burden in the gut. In addition to the known effects of proton pump inhibitors (PPIs) as

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“…Numerous fungal species, from yeasts and yeast-like fungi to molds, constitute human mycobiome and inhabit the gastrointestinal tract of healthy individuals [1]. However, the gut-resident fungi can translocate from the gut to the bloodstream and cause lethal invasive fungal infection (IFI) when the immune system is impaired [2]. Fungi profoundly affect human health.…”

Section: Introductionmentioning

confidence: 99%

The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

Arastehfar

Lass‐Flörl

Garcia-Rubio

et al. 2020

JoF

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Human fungal pathogens are attributable to a significant economic burden and mortality worldwide. Antifungal treatments, although limited in number, play a pivotal role in decreasing mortality and morbidities posed by invasive fungal infections (IFIs). However, the recent emergence of multidrug-resistant Candida auris and Candida glabrata and acquiring invasive infections due to azole-resistant C. parapsilosis, C. tropicalis, and Aspergillus spp. in azole-naïve patients pose a serious health threat considering the limited number of systemic antifungals available to treat IFIs. Although advancing for major fungal pathogens, the understanding of fungal attributes contributing to antifungal resistance is just emerging for several clinically important MDR fungal pathogens. Further complicating the matter are the distinct differences in antifungal resistance mechanisms among various fungal species in which one or more mechanisms may contribute to the resistance phenotype. In this review, we attempt to summarize the burden of antifungal resistance for selected non-albicansCandida and clinically important Aspergillus species together with their phylogenetic placement on the tree of life. Moreover, we highlight the different molecular mechanisms between antifungal tolerance and resistance, and comprehensively discuss the molecular mechanisms of antifungal resistance in a species level.

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High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis

Cited by 202 publications

References 54 publications

Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report

Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report

The gut mycobiome: The overlooked constituent of clinical outcomes and treatment complications in patients with cancer and other immunosuppressive conditions

The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

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