Effect of Nicotinamide Against Candida albicans

被引：29

作者：

Xing, XinRui ^{[1
]}

Liao, ZeBin ^{[2
,3
]}

Tan, Fei ^{[1
]}

Zhu, ZhenYu ^{[2
]}

Jiang, Yuanying ^{[4
]}

Cao, YingYing ^{[1
]}

机构：

[1] Tongji Univ, Shanghai Skin Dis Hosp, Sch Med, Shanghai, Peoples R China

[2] Second Mil Med Univ, Sch Pharm, Shanghai, Peoples R China

[3] Second Mil Med Univ, Fac Naval Med, Dept Radiat Med, Shanghai, Peoples R China

[4] Tongji Univ, Shanghai Peoples Hosp 10, Dept Pharmacol, Sch Med, Shanghai, Peoples R China

来源：

FRONTIERS IN MICROBIOLOGY | 2019年 / 10卷

基金：

中国国家自然科学基金;

关键词：

nicotinamide; Candida albicans; drug resistance; fluconazole; GIN4; HIGH-DOSE NICOTINAMIDE; IN-VITRO; KINASE GIN4; SEPTIN; PHOSPHORYLATION; FLUCONAZOLE; INHIBITION; FALCIPARUM; BERBERINE; RESISTANT;

D O I：

10.3389/fmicb.2019.00595

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Nicotinamide (NAM) has a long history in clinical applications and can be safely used for treating various diseases. In recent years, NAM was found to exhibit antimicrobial activities, inhibiting the growth of Plasmodium falciparum, Mycobacterium tuberculosis, and human immunodeficiency virus (HIV). Here we investigated the activity of NAM against Candida albicans, one of the most prevalent human fungal pathogens. Our results showed that NAM exhibited significant antifungal activity against C. albicans, including fluconazole-resistant isolates. NAM could also effectively suppress biofilm formation. In addition, NAM exhibited antifungal activity against non-Candida albicans species and Cryptococcus neoformans. Combination of NAM and fluconazole showed an even strong antifungal activity. The antifungal activity of NAM was further confirmed in a mouse model of disseminated candidiasis. Confocal laser scanning microscopy revealed that NAM increased cell wall beta-glucans exposure and chitin content while decreased mannan level. Furthermore, by screening the C. albicans homozygous deletion mutant library, the C. albicans mutant lacking GIN4, which encodes a septin regulatory protein kinase and is essential for the maintenance of cell wall integrity, was identified to be high sensitive to NAM. These findings suggested that NAM might exhibit antifungal activities through affecting cell wall organization.

引用

页数：9

共 39 条

[1] Control of mitotic events by Nap1 and the Gin4 kinase [J].

Altman, R ;

Kellogg, D .

JOURNAL OF CELL BIOLOGY, 1997, 138 (01) :119-130

[2] Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against Candida albicans [J].

Badrane, Hassan ;

Nguyen, M. Hong ;

Clancy, Cornelius J. .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2016, 60 (06) :3591-3600

[3] COENZYME Q(10) AND NICOTINAMIDE BLOCK STRIATAL LESIONS PRODUCED BY THE MITOCHONDRIAL TOXIN MALONATE [J].

BEAL, MF ;

HENSHAW, DR ;

JENKINS, BG ;

ROSEN, BR ;

SCHULZ, JB .

ANNALS OF NEUROLOGY, 1994, 36 (06) :882-888

[4] Responding to the emergence of antifungal drug resistance: perspectives from the bench and the bedside [J].

Beardsley, Justin ;

Halliday, Catriona L. ;

Chen, Sharon C-A ;

Sorrell, Tania C. .

FUTURE MICROBIOLOGY, 2018, 13 (10) :1175-1191

[5] Antifungal resistance of candidal biofilms formed on denture acrylic in vitro [J].

Chandra, J ;

Mukherjee, PK ;

Leidich, SD ;

Faddoul, FF ;

Hoyer, LL ;

Douglas, LJ ;

Ghannoum, MA .

JOURNAL OF DENTAL RESEARCH, 2001, 80 (03) :903-908

[6] A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention [J].

Chen, Andrew C. ;

Martin, Andrew J. ;

Choy, Bonita ;

Fernandez-Penas, Pablo ;

Dalziell, Robyn A. ;

McKenzie, Catriona A. ;

Scolyer, Richard A. ;

Dhillon, Haryana M. ;

Vardy, Janette L. ;

Kricker, Anne ;

St George, Gayathri ;

Chinniah, Niranthari ;

Halliday, Gary M. ;

Damian, Diona L. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1618-1626

[7] Nicotinamide and the skin [J].

Chen, Andrew C. ;

Damian, Diona L. .

AUSTRALASIAN JOURNAL OF DERMATOLOGY, 2014, 55 (03) :169-175

[8] Genetic control of Candida albicans biofilm development [J].

Finkel, Jonathan S. ;

Mitchell, Aaron P. .

NATURE REVIEWS MICROBIOLOGY, 2011, 9 (02) :109-118

[9] The global transcriptional response to transient cell wall damage in Saccharomyces cerevisiae and its regulation by the cell integrity signaling pathway [J].

García, R ;

Bermejo, C ;

Grau, C ;

Pérez, R ;

Rodríguez-Peña, JM ;

Francois, J ;

Nombela, C ;

Arroyo, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (15) :15183-15195

[10] Septin-associated protein kinase Gin4 affects localization and phosphorylation of Chs4, the regulatory subunit of the Baker's yeast chitin synthase III complex [J].

Gohlke, Simon ;

Heine, Daniela ;

Schmitz, Hans-Peter ;

Merzendorfer, Hans .

FUNGAL GENETICS AND BIOLOGY, 2018, 117 :11-20

← 1 2 3 4 →