Analysis of the essentiality of ROM2 genes in the pathogenic yeasts Candida glabrata and Candida albicans using temperature-sensitive mutants

被引:4
作者
Kanno, T. [1 ]
Takekawa, D. [1 ]
Miyakawa, Y. [1 ]
机构
[1] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Div Biotechnol, Kofu, Yamanashi 4008510, Japan
关键词
antifungal targets; Candida albicans; Candida glabrata; cell lysis; essential genes; point mutation; ROM2; temperature-sensitive mutants; INVASIVE FUNGAL-INFECTIONS; BACILLUS-SUBTILIS; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; SEPTUM FORMATION; INTENSIVE-CARE; CELL-CYCLE; SECA GENE; SYSTEM; IDENTIFICATION;
D O I
10.1111/jam.12745
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
AimsTo analyse the essentiality of the ROM2 genes originating from the pathogenic yeasts Candida glabrata and Candida albicans by using temperature-sensitive (ts) mutants. Methods and ResultsBased on the general concepts that ts mutations are generated by virtue of point mutation within essential genes, we have previously established a novel method (termed ETS system' for screening and identification of essential genes using ts mutants of C.glabrata). According to this ETS system, the present study successfully identified a putative C.glabrata ROM2 homologue as an essential gene that complements its point mutation (Cys-1275/Tyr substitution). The C.albicans ROM2 mutant (Cys-1281/Tyr), constructed patterned after this point mutation, also displayed ts phenotype. Both ts mutants recovered colony-forming ability, with concomitant suppression of lysis phenotype, at the elevated temperature in the presence of 1moll(-1) sorbitol as an osmotic stabilizer. Sequence alignment revealed that human genome possesses relatively low homology against Rom2 homologues, which are highly conserved among yeast species. ConclusionsROM2 genes of C.glabrata and C.albicans are essential for viability, probably involved in cell wall integrity. Significance and Impact of the StudyROM2 genes essential for both Candida species may be a potentially useful antifungal targets from chemotherapeutic viewpoint.
引用
收藏
页码:851 / 863
页数:13
相关论文
共 40 条
[31]   Emerging Invasive Fungal Diseases in Transplantation [J].
Parize, Perrine ;
Rammaert, Blandine ;
Lortholary, Olivier .
CURRENT INFECTIOUS DISEASE REPORTS, 2012, 14 (06) :668-675
[32]   Epidemiology of invasive candidiasis: a persistent public health problem [J].
Pfaller, M. A. ;
Diekema, D. J. .
CLINICAL MICROBIOLOGY REVIEWS, 2007, 20 (01) :133-+
[33]   Antifungal Drug Resistance: Mechanisms, Epidemiology, and Consequences for Treatment [J].
Pfaller, Michael A. .
AMERICAN JOURNAL OF MEDICINE, 2012, 125 (01) :S3-S13
[34]   Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery [J].
Roemer, T ;
Jiang, B ;
Davison, J ;
Ketela, T ;
Veillette, K ;
Breton, A ;
Tandia, F ;
Linteau, A ;
Sillaots, S ;
Marta, C ;
Martel, N ;
Veronneau, S ;
Lemieux, S ;
Kauffman, S ;
Becker, J ;
Storms, R ;
Boone, C ;
Bussey, H .
MOLECULAR MICROBIOLOGY, 2003, 50 (01) :167-181
[35]  
SADAIE Y, 1991, GENE, V98, P101
[36]  
Sherman F., 1986, LAB COURSE MANUAL ME
[37]   Invasive fungal infections in patients with cancer in the Intensive Care Unit [J].
Sipsas, Nikolaos V. ;
Kontoyiannis, Dimitrios P. .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2012, 39 (06) :464-471
[38]   INVIVO AND INVITRO CHARACTERIZATION OF THE SECA GENE-PRODUCT OF BACILLUS-SUBTILIS [J].
TAKAMATSU, H ;
FUMA, S ;
NAKAMURA, K ;
SADAIE, Y ;
SHINKAI, A ;
MATSUYAMA, S ;
MIZUSHIMA, S ;
YAMANE, K .
JOURNAL OF BACTERIOLOGY, 1992, 174 (13) :4308-4316
[39]   The Use of Antifungal Therapy in Neonatal Intensive Care [J].
Testoni, Daniela ;
Smith, P. Brian ;
Benjamin, Daniel K., Jr. .
CLINICS IN PERINATOLOGY, 2012, 39 (01) :83-+
[40]   Regulation of the cell integrity pathway by rapamycin-sensitive TOR function in budding yeast [J].
Torres, J ;
Di Como, CJ ;
Herrero, E ;
de la Torre-Ruiz, MA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (45) :43495-43504