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J Clin Microbiol. 2018 Sep 25;56(10). pii: e00746-18. doi: 10.1128/JCM.00746-18. Print 2018 Oct.

PCR-Based Approach Targeting Mucorales-Specific Gene Family for Diagnosis of Mucormycosis.

Author information

1
Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, Torrance, California, USA.
2
Sharjah Institute for Medical Research, and College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.
3
Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
4
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, German Centre for Infection Research (DZIF), partner site Bonn-Cologne, and Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.
5
Divsion of Hematology/Oncology, University of Florida College of Medicine, Gainesville, Florida, USA.
6
California Institute for Medical Research, San Jose, California, USA.
7
The Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California, USA.
8
David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California, USA.
9
Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, Torrance, California, USA ibrahim@labiomed.org.
10
Vitalex Biosciences, Irvine, California, USA.

Abstract

Mucormycosis is an aggressive, life-threatening infection caused by fungi in the order Mucorales. The current diagnosis of mucormycosis relies on mycological cultures, radiology and histopathology. These methods lack sensitivity and are most definitive later in the course of infection, resulting in the prevention of timely intervention. PCR-based approaches have shown promising potential in rapidly diagnosing mucormycosis. The spore coating protein homolog encoding CotH genes are uniquely and universally present among Mucorales. Thus, CotH genes are potential targets for the rapid diagnosis of mucormycosis. We infected mice with different Mucorales known to cause human mucormycosis and investigated whether CotH could be PCR amplified from biological fluids. Uninfected mice and those with aspergillosis were used to determine the specificity of the assay. CotH was detected as early as 24 h postinfection in plasma, urine, and bronchoalveolar lavage (BAL) samples from mice infected intratracheally with Rhizopus delemar, Rhizopus oryzae, Mucor circinelloides, Lichtheimia corymbifera, or Cunninghamella bertholletiae but not from samples taken from uninfected mice or mice infected with Aspergillus fumigatus Detection of CotH from urine samples was more reliable than from plasma or BAL fluid. Using the receiver operating characteristic method, the sensitivity and the specificity of the assay were found to be 90 and 100%, respectively. Finally, CotH was PCR amplified from urine samples of patients with proven mucormycosis. Thus, PCR amplification of CotH is a promising target for the development of a reliable, sensitive, and simple method of early diagnosis of mucormycosis.

KEYWORDS:

CotH; Cunninghamella; Lichtheimia; Mucor; Mucorales; Rhizopus; diagnosis

PMID:
30068535
PMCID:
PMC6156309
[Available on 2019-03-25]
DOI:
10.1128/JCM.00746-18

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