Publication: Evolution of the Sterol Biosynthetic Pathway of Pythium insidiosum and Related Oomycetes Contributes to Antifungal Drug Resistance
Issued Date
2017
Resource Type
Language
eng
Rights
Mahidol University
Rights Holder(s)
American Society for Microbiology
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.61, No.4 (2017), 1-14
Suggested Citation
Tassanee Lerksuthirat, Areeporn Sangcakul, Tassanee Lohnoo, Wanta Yingyong, Thidarat Rujirawat, Theerapong Krajaejun Evolution of the Sterol Biosynthetic Pathway of Pythium insidiosum and Related Oomycetes Contributes to Antifungal Drug Resistance. Antimicrobial Agents and Chemotherapy. Vol.61, No.4 (2017), 1-14. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/61242
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Evolution of the Sterol Biosynthetic Pathway of Pythium insidiosum and Related Oomycetes Contributes to Antifungal Drug Resistance
Abstract
Pythiosis is a life-threatening infectious disease caused by the oomycete
Pythium insidiosum. Direct exposure to Py. insidiosum zoospores can initiate infections of the eye, limb, gastrointestinal tract, or skin/subcutaneous tissue. Treatments
for pythiosis have mostly relied on surgery. Antifungal drugs are generally ineffective
against Py. insidiosum. However, one patient with an invasive Py. insidiosum infection
recovered completely following treatment with terbinafine and itraconazole. Additionally, the drug target sterol biosynthetic enzymes have been identified in the oomycete Aphanomyces euteiches. It remains an open question whether Py. insidiosum
is susceptible to the antifungal drugs and harbors any of the known drug target enzymes. Here, we determined the in vitro susceptibilities of terbinafine and itraconazole against 30 isolates of Py. insidiosum. We also analyzed endogenous sterols and
searched for genes encoding the sterol biosynthetic enzymes in the genomes of Py.
insidiosum and related oomycetes. The susceptibility assay showed that the growth
of each of the Py. insidiosum isolates was inhibited by the antifungal agents, but
only at difficult-to-achieve concentrations, which explains the clinical resistance of
the drugs in the treatment of pythiosis patients. Genome searches of Py. insidiosum
and related oomycetes demonstrated that these organisms contained an incomplete
set of sterol biosynthetic enzymes. Gas chromatographic mass spectrometry did not
detect any sterol end products in Py. insidiosum. In conclusion, Py. insidiosum possesses an incomplete sterol biosynthetic pathway. Resistance to antifungal drugs targeting enzymes in the ergosterol biosynthetic pathway in Py. insidiosum was due to
modifications or losses of some of the genes encoding the drug target enzymes.