Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility

Proctor, Diana M.; Dangana, Thelma; Sexton, D. Joseph; Fukuda, Christine; Yelin, Rachel D; Stanley, Mary; Bell, Pamela; Baskaran, Sangeetha Ananda; Deming, Clay; Chen, Qiong; Conlan, Sean; Park, Morgan; Welsh, Rory M.; Vallabhaneni, Snigdha; Chiller, Tom; Forsberg, Kaitlin; Black, Stéphanie; Pacilli, Massimo; Kong, Heidi H.; Lin, Michael; Schoeny, Michael; Litvintseva, Anastasia P.; Segre, Julia A.; Hayden, Mary K

doi:10.1038/s41591-021-01383-w

Cited by 95 publications

(118 citation statements)

References 44 publications

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“…An interesting result was obtained for Candida auris, an important emerging fungal pathogen, which was first described in 2009 and has spread across six continents as a cause of infections in hospitals (Meis and Chowdhary, 2018;Proctor et al, 2021). Both C2 and C10 were found to strongly suppress the growth of C. auris with a similar IC 50 (around 30 μg/ ml).…”

Section: The Antimicrobial Spectrum Of Three Representative β-Carbolinesmentioning

confidence: 94%

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Peng

et al. 2021

Front. Pharmacol.

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The stem of Picrasma quassioides (PQ) was recorded as a prominent traditional Chinese medicine, Kumu, which was effective for microbial infection, inflammation, fever, and dysentery, etc. At present, Kumu is widely used in China to develop different medicines, even as injection (Kumu zhusheye), for combating infections. However, the chemical basis of its antimicrobial activity has still not been elucidated. To examine the active chemicals, its stem was extracted to perform bioassay-guided purification against Staphylococcus aureus and Escherichia coli. In this study, two types of columns (normal and reverse-phase) were used for speedy bioassay-guided isolation from Kumu, and the active peaks were collected and identified via an UHPLC-Orbitrap-Ion Trap Mass Spectrometer, combined with MS Fragmenter and ChromGenius. For identification, the COCONUT Database (largest database of natural products) and a manually built PQ database were used, in combination with prediction and calculation of mass fragmentation and retention time to better infer their structures, especially for isomers. Moreover, three standards were analyzed under different conditions for developing and validating the MS method. A total of 25 active compounds were identified, including 24 alkaloids and 1 triterpenoid against S. aureus, whereas only β-carboline-1-carboxylic acid and picrasidine S were active against E. coli. Here, the good antimicrobial activity of 18 chemicals was reported for the first time. Furthermore, the spectrum of three abundant β-carbolines was assessed via their IC50 and MBC against various human pathogens. All of them exhibited strong antimicrobial activities with good potential to be developed as antibiotics. This study clearly showed the antimicrobial chemical basis of Kumu, and the results demonstrated that HRMS coupled with MS Fragmenter and ChromGenius was a powerful tool for compound analysis, which can be used for other complex samples. Beta-carbolines reported here are important lead compounds in antibiotic discovery.

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Section: The Antimicrobial Spectrum Of Three Representative β-Carbolinesmentioning

confidence: 94%

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Peng

et al. 2021

Front. Pharmacol.

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“…In fact, occult colonization has been shown to facilitate the persistence of outbreaks involving other pathogens, such as Klebsiella pneumoniae [ 28 ]. There are still limited published data about the relative sensitivity of different body sites to detect C. auris , although it has been reported that at least six body sites would be necessary to detect all colonized patients [ 29 ]. However, sampling six body parts is not affordable for large-scale routine screening, and it is recommended to target high-yield sites [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Chromogenic Medium CHROMagarTM Candida Plus for Detection of Candida auris and Other Candida Species from Surveillance and Environmental Samples: A Multicenter Study

García

Palop

Martin

et al. 2022

JoF

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Epidemiological trends show a dramatic increase in the prevalence of fungal infections, and in the isolation of multidrug-resistant species, such as Candida auris. CHROMagarTM Candida (CC; CHROMagar, Paris, France) and other chromogenic media, which are widely used in the clinical laboratory because they allow a rapid identification of most Candida species. Recently, CHROMagarTM Candida Plus (CC-Plus; CHROMagar, Paris, France) was developed to detect and differentiate C. auris in addition to other major clinical Candida species, such as C. albicans, C. tropicalis, C. glabrata, or C. krusei. C. auris colonies display a differential light blue color with a blue halo. A multicentric study was designed to evaluate the performance of the CC-Plus medium in the detection of Candida species in patients’ surveillance and environmental samples from three Spanish hospitals with active C. auris outbreaks. A total of 364 patients’ surveillance samples and 212 environmental samples were tested. Samples were inoculated in CC and CC-Plus in parallel, and the plates were read at 24 and 48 h. All recovered colonies were presumptively identified according to colony color described by manufacturer, and the definitive identification was performed by mass spectrometry at 48 h. A total of 134 C. auris isolates were obtained (101 from patients’ surveillance samples, and 33 from environmental samples). Sensitivity, specificity, and predictive positive and negative values were 99.5%, 100%, 100%, and 99.1%, respectively, for the main clinical Candida species, showing that CC-Plus is comparable to CC, with the advantage of being able to differentiate C. auris from C. parapsilosis. Furthermore, CC-Plus was able to detect one C. albicans, one C. glabrata, and eight C. auris that did not grow in CC. Additionally, the yeast colonies were generally larger, suggesting that this novel medium could be a richer medium, and suitable for surveillance and environmental cultures of C. auris and other clinically relevant Candida species.

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“…It has been found that fungi are also an integral part of the microbiome and thus the term "mycobiome" has been used to describe Microorganisms 2022, 10, 330 2 of 10 these communities [15,16]. Recent modeling dynamics of the human mycobiome have provided insight into underlying alterations of the skin fungal community as a possible modifiable risk factor for acquisition and persistence of C. auris [17]. As of now, the systemic pathobiology of C. auris in the absence of a microbiota has not been described.…”

Section: Introductionmentioning

confidence: 99%

Depletion of the Microbiota Has a Modest but Important Impact on the Fungal Burden of the Heart and Lungs during Early Systemic Candida auris Infection in Neutropenic Mice

et al. 2022

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The progression and systemic pathobiology of C. auris in the absence of a microbiota have not been described. Here, we describe the influence of the microbiota during the first 5 days of C. auris infection in germ-free or antibiotic-depleted mice. Depletion of the bacterial microbiota in both germ-free and antibiotic-depleted models results in a modest but important increase in the early stages of C. auris infection. Particularly the heart and lungs, followed by the cecum, uterus, and stomach, of intravenously (i.v.) infected neutropenic mice showed significant fungal organ burden. Understanding disease progression and pathobiology of C. auris in individuals with a depleted microbiota could potentially help in the development of care protocols that incorporate supplementation or restoration of the microbiota before invasive procedures, such as transplantation surgeries.

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Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility

Cited by 95 publications

References 44 publications

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Bioassay-Guided Interpretation of Antimicrobial Compounds in Kumu, a TCM Preparation From Picrasma quassioides’ Stem via UHPLC-Orbitrap-Ion Trap Mass Spectrometry Combined With Fragmentation and Retention Time Calculation

Novel Chromogenic Medium CHROMagarTM Candida Plus for Detection of Candida auris and Other Candida Species from Surveillance and Environmental Samples: A Multicenter Study

Depletion of the Microbiota Has a Modest but Important Impact on the Fungal Burden of the Heart and Lungs during Early Systemic Candida auris Infection in Neutropenic Mice

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