ram1 gene, encoding a subunit of farnesyltransferase, contributes to growth, antifungal susceptibility to amphotericin B of Aspergillus fumigatus.
Farnesylation, which is catalyzed by farnesyltransferase, is an important posttranslational process. The function of farnesyltransferase has been previously explored in Cryptococcus neoformans and Candida albicans. Aspergillus fumigatus is an important human opportunistic fungal pathogen in immunocompromised patients. Here we discover the role of the ram1 gene, encoding the β-subunit of farnesyltransferase in A. fumigatus, in the fungal growth and antifungal susceptibility. In this study the ram1 gene was disrupted using A. tumefaciens-mediated transformation. The morphology and radial growth of Δram1 were observed. Assays of disk diffusion and broth microdilution were used to determine the susceptibility of Δram1 mutant to commonly clinical used antifungals and the farnesyltransferase inhibitor manumycin A. Deletion of ram1 resulted in a reduced radial growth of A. fumigatus but did not affect the microscopic morphology. Δram1 showed increased susceptibility to the antifungal amphotericin B; however, its susceptibility to azoles and caspofungin was the same to that to the parental strain. Our data indicate that farnesyltransferase is a potential target for design new antifungal agents.
Department of Dermatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Jianjun
J
Qiao
Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Yan
Y
Song
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Zongxin
Z
Ling
Department of Intensive Care Unit, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Xia
X
Liu
Department of Dermatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Hong
H
Fang
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D008826:Microbial Sensitivity Tests; D011090:Polyenes / Q000009:adverse effects / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000009:adverse effects / Q000494:pharmacology*; D054876:Prenylation
D000935:Antifungal Agents; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D000666:Amphotericin B; D051231:Farnesyltranstransferase; C054474:manumycin
Aspergillus fumigatus; amphotericin B; antifungal susceptibility; farnesyltransferase; ram1 gene