Ref ID: 19595
Author:
Umeyama1*, S Yamagoe1, K Tanabe1, M Nagi1, H Ohno1, Y Miyazaki1
Author address:
1Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan
Full conference title:
6th Advances Against Aspergillosis 2014
Abstract:
Purpose:
Protein kinase is a key enzyme that functionally changes the target protein by phosphorylation. It is
involved in the regulation of many cellular pathways including signal transduction. In mammalian
cells, polo-like kinase (Plk) plays essential roles in the regulation of both mitosis and cytokinesis,
and is an attractive target for the development of antitumor agents. To explore the possibility of
using Plk as a target for antifungal therapies, we investigated the involvement of a Plk homolog,
AfPLK1, in the regulation of hyphal growth in Aspergillus fumigatus.
Methods:
The A. fumigatus 916;akuA strain AfS35 was transformed with a deletion cassette comprised of 1-kb
regions upstream and downstream of AfPLK1 flanking a hygromycin resistance cassette, generating
the 916;Afplk1 disruptant strain. To generate a complemented strain, the 916;Afplk1 strain was transformed
with a DNA cassette containing AfPLK1 and a pyrithiamine resistance gene.
Results:
The successful construction of a deletion strain demonstrated that AfPLK1 was not essential for
the growth of A. fumigatus. The 916;Afplk1 disruptant strain exhibited a reduced colony growth rate
of approximately 60% compared with the wild-type strain on PDA or AMM agar plates at 37°C.
Conidiation by the 916;Afplk1 disruptant strain dramatically decreased because of the development of
immature conidiophores. In liquid AMM media, branching of subapical hyphae was observed in 50%
of hyphal cells of the disruptant grown at 37°C for 11 h, whereas the wild-type and complemented
strains did not show any branching of hyphae under these conditions.
Conclusion:
AfPlk1 plays an important role in the regulation of hyphal elongation, conidiation, and cell polarity.
The possibility of its use as a potential target for the development of novel antifungal agents against
aspergillosis will be examined in future animal studies.
Abstract Number: 120
Conference Year: 2014
Link to conference website: http://www.AAA2014.org
New link: NULL
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