Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata

被引：31

作者：

Chew, Shu Yih ^{[1
]}

Ho, Kok Lian ^{[2
]}

Cheah, Yoke Kqueen ^{[3
]}

Ng, Tzu Shan ^{[4
]}

Sandai, Doblin ^{[5
]}

Brown, Alistair J. P. ^{[6
]}

Than, Leslie Thian Lung ^{[1
]}

机构：

[1] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Med Microbiol & Parasitol, Upm Serdang 43400, Selangor, Malaysia

[2] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Pathol, Upm Serdang 43400, Selangor, Malaysia

[3] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Biomed Sci, Upm Serdang 43400, Selangor, Malaysia

[4] Univ Malaya, Fac Med, Dept Mol Med, Kuala Lumpur 50603, Malaysia

[5] Univ Sains Malaysia, Adv Med & Dent Inst, Infect Cluster, Kepala Batas 13200, Pulau Pinang, Malaysia

[6] Univ Aberdeen, Inst Med Sci, MRC Ctr Med Mycol, Aberdeen AB25 2ZD, Scotland

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

ISOCITRATE LYASE; ASPERGILLUS-FUMIGATUS; CARBON UTILIZATION; MACROPHAGE; PATHWAYS; SURVIVAL; ALBICANS;

D O I：

10.1038/s41598-019-39117-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The human fungal pathogen Candida glabrata appears to utilise unique stealth, evasion and persistence strategies in subverting the onslaught of host immune response during systemic infection. However, macrophages actively deprive the intracellular fungal pathogen of glucose, and therefore alternative carbon sources probably support the growth and survival of engulfed C. glabrata. The present study aimed to investigate the role of the glyoxylate cycle gene ICL1 in alternative carbon utilisation and its importance for the virulence of C. glabrata. The data showed that disruption of ICL1 rendered C. glabrata unable to utilise acetate, ethanol or oleic acid. In addition, C. glabrata icl1 Delta cells displayed significantly reduced biofilm growth in the presence of several alternative carbon sources. It was also found that ICL1 is crucial for the survival of C. glabrata in response to macrophage engulfment. Disruption of ICL1 also conferred a severe attenuation in the virulence of C. glabrata in the mouse model of invasive candidiasis. In conclusion, a functional glyoxylate cycle is essential for C. glabrata to utilise certain alternative carbon sources in vitro and to display full virulence in vivo. This reinforces the view that antifungal drugs that target fungal Icl1 have potential for future therapeutic intervention.

引用

页数：11

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