2OO9 – 2O1O - Faculty of Dentistry - University of Otago

KYOKO NIIMI
DVM (Nihon Vet) PhD (Otago)
Oral Sciences
Senior Research Fellow
Dr Niimi’s research interests are in microbiology/
mycology research and the development of antifungal
agents, with three main areas of research expertise: the
molecular biology of human fungal pathogens Candida
albicans and C. glabrata; the mechanisms of antifungal
resistance and drug development; and heterologous
protein expression in the yeast Saccharomyces cerevisiae.
Research and Collaboration
Dr Niimi’s research scope in 2009 and 2010 was twofold.
Investigating mechanisms of echinocandin resistance in
human fungal pathogens Candida albicans and C. glabrata.
A novel class of antifungal agent, the echinocandins,
provides new therapeutic options for the treatment of
fungal infections caused by Candida species. The incidence
of echinocandin resistance remains low; however, there
are some reports of echinocandin resistant isolates
from patients with treatment failure. It was found that
mutations in two alleles of diploid C. albicans and two
separate genes of haploid C. glabrata are required for the
acquisition of high-level resistance, which may be why
clinically significant echinocandin resistance is rare. Key
collaborators in the project include Drs K. Maki and K.
Hatakenaka of Astellas Pharma Inc., Japan; Assoc. Prof. H.
Nakayama, Suzuka University of Medical Sciences, Japan;
Assoc. Prof. H. Chibana and Dr K. Ueno, Chiba University,
Japan; Drs A. Hirai, T. Umeyama, K. Tanabe and Niimi, M.,
National Institute of Infectious Diseases, Japan; Drs B.
C. Monk, Woods, M. A. and Prof. R. D. Cannon of the
Molecular Microbiology Laboratory, University of Otago.
Modifying the heterologous membrane expression
system to maximize protein expression. The heterologous
membrane expression system in baker’s yeast was
developed in the Molecular Microbiology Laboratory
(MML). The system needs to be further improved to
achieve high level expression of human membrane proteins
(such as Abcb1p, Abcg2p or Abcb5p) that are involved
in drug resistance in human cancer cells. Mutant cells
were selected which possessed higher drug efflux activity,
by UV irradiation followed by genetic engineering. Key
collaborators include Professor R. D. Cannon, Drs B. C.
Monk, M. Niimi, E. Lamping, A. R. Holmes, M. Keniya of MML;
Assoc Prof. S. Kajiwara, Tokyo Institute of Technology, Japan.
46 FACULTY OF DENTISTRY RESEARCH REPORT 2009-2010
Recent Publications
Niimi K, Monk BC, Hirai A, Hatakenaka K, Umeyama T,
Lamping E, Maki K, Tanabe K, Kamimura T, Ikeda F, Uehara
Y, Kano R, Hasegawa A, Cannon RD, Niimi M. Clinically
significant micafungin-resistance in Candida albicans
involves modification of a glucan synthase catalytic subunit
GSC1 (FKS1) allele followed by loss of heterozygosity.
Journal of Antimicrobial Chemotherapy 65: 842-852 (2010).
Cannon RD, Lamping E, Holmes AR, Niimi K, Baret PV,
Keniya MV, Tanabe K, Niimi M, Goffeau A, Monk BC.
Efflux-mediated fungal drug resistance. Clinical Microbiology
Reviews 22: 291-321 (2009).
Lamping E, Ranchod A, Nakamura K, Tyndall JDA, Niimi K,
Holmes AR, Niimi M, Cannon RD. Abc1p is a multidrug
efflux transporter that tips the balance in favor of innate
azole resistance in Candida krusei. Antimicrobial Agents and
Chemotherapy 53: 354-369 (2009).
Niimi K, Niimi M. Mechanisms of echinocandin resistance
in pathogenic fungi. Japanese Journal of Medical Mycology
50: 57-66 (2009).