Methylcitrate cycle gene MCD is essential for the virulence of Talaromyces marneffei

Jiao Feng, Liya He, Xing Xiao, Zhiwen Chen, Chunmei Chen, Jieming Chu, Sha Lu, Xiqing Li, Eleftherios Mylonakis, Liyan Xi

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Talaromyces marneffei (T. marneffei), which used to be known as Penicillium marneffei, is the causative agent of the fatal systemic mycosis known as talaromycosis. For the purpose of understanding the role of methylcitrate cycle in the virulence of T. marneffei, we generated MCD deletion (ΔMCD) and complementation (ΔMCD+) mutants of T. marneffei. Growth in different carbon sources showed that ΔMCD cannot grow on propionate media and grew slowly on the valerate, valine, methionine, isoleucine, cholesterol, and YNB (carbon free) media. The macrophage killing assay showed that ΔMCD was attenuated in macrophages of mice in vitro, especially at the presence of propionate. Finally, virulence studies in a murine infection experiment revealed attenuated virulence of the ΔMCD, which indicates MCD is essential for T. marneffei virulence in the host. This experiment laid the foundation for the further study of the specific mechanisms underlying the methylcitrate cycle of T. marneffei and may provide suitable targets for new antifungals.

Original languageEnglish (US)
Pages (from-to)351-361
Number of pages11
JournalMedical Mycology
Volume58
Issue number3
DOIs
StatePublished - Apr 1 2020

Keywords

  • Talaromyces marneffei
  • methylcitrate dehydratase
  • the methylcitrate cycle
  • virulence

ASJC Scopus subject areas

  • Infectious Diseases

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