Deletion of the sec4 homolog srgA from Aspergillus fumigatus is associated with an impaired stress response, attenuated virulence and phenotypic heterogeneity.
Deletion of the sec4 homolog srgA from Aspergillus fumigatus is associated with an impaired stress response, attenuated virulence and phenotypic heterogeneity.
复制标题
DOI：
10.1371/journal.pone.0066741
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Askew DS
中科院分区：
文献类型：
--
作者：
Powers-Fletcher MV;Feng X;Krishnan K;Askew DS
Small GTPases of the Rab family are master regulators of membrane trafficking, responsible for coordinating the sorting, packaging and delivery of membrane-bound vesicles to specific sites within eukaryotic cells. The contribution of these proteins to the biology of the human pathogenic fungus Aspergillus fumigatus has not been explored. In this study, we characterized the srgA gene, encoding a Rab GTPase closely related to Sec4. We found that a GFP-SrgA fusion protein accumulated preferentially at hyphal tips and mature condiophores. The radial growth of a ΔsrgA mutant was impaired on both rich and minimal medium, consistent with a role for SrgA in filamentous growth. In addition, the ΔsrgA mutant revealed dysmorphic conidiophores that produced conidia with heterogeneous morphology. The ΔsrgA mutant was hypersensitive to brefeldin A-mediated inhibition of vesicular trafficking and showed increased temperature sensitivity relative to wild type A. fumigatus. However, the most striking phenotype of this mutant was its phenotypic heterogeneity. Individual colonies isolated from the original ΔsrgA mutant showed variable morphology with colony sectoring. In addition, each isolate of the ΔsrgA mutant displayed divergent phenotypes with respect to thermotolerance, in vitro stress response and virulence in a Galleria mellonella infection model. Taken together, these results indicate that SrgA contributes to the asexual development and filamentous growth of A. fumigatus. However, the discordant phenotypes observed among individual isolates of the ΔsrgA mutant suggest that the absence of srgA exerts selective pressure for the acquisition of compensatory changes, such as second-site suppressor mutations.
登录
查看更多内容
影响因子：
3.6
作者：
Joubert, A.;Simoneau, P.;Guillemette, T.
通讯作者：
Guillemette, T.
影响因子：
11.4
作者：
HAUBRUCK, H;ENGELKE, U;GALLWITZ, D
通讯作者：
GALLWITZ, D
影响因子：
3.2
作者：
Mao, YX;Kalb, VF;Wong, B
通讯作者：
Wong, B
DOI：
10.1007/978-1-61779-539-8_33
发表时间：
2012-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Fallon, John;Kelly, Judy;Kavanagh, Kevin
通讯作者：
Kavanagh, Kevin
DOI：
10.1083/jcb.200201003
发表时间：
2002-06-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ortiz D;Medkova M;Walch-Solimena C;Novick P
通讯作者：
Novick P