TY - JOUR
T1 - Methylcitrate cycle gene MCD is essential for the virulence of Talaromyces marneffei
AU - Feng, Jiao
AU - He, Liya
AU - Xiao, Xing
AU - Chen, Zhiwen
AU - Chen, Chunmei
AU - Chu, Jieming
AU - Lu, Sha
AU - Li, Xiqing
AU - Mylonakis, Eleftherios
AU - Xi, Liyan
N1 - Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - Talaromyces marneffei
KW - methylcitrate dehydratase
KW - the methylcitrate cycle
KW - virulence
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U2 - 10.1093/mmy/myz063
DO - 10.1093/mmy/myz063
M3 - Article
C2 - 31290549
AN - SCOPUS:85074511793
SN - 1369-3786
VL - 58
SP - 351
EP - 361
JO - Medical Mycology
JF - Medical Mycology
IS - 3
ER -