A conserved G protein (Drg1p) plays a role in regulation of invasive filamentation in Candida albicans

Chen, Xi; Kumamoto, Carol A.

doi:10.1099/mic.0.29246-0

Cited by 11 publications

(7 citation statements)

References 27 publications

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“…The promoter region of EFG1 was cloned upstream of the gene encoding yeast enhanced green fluorescent protein (yEGFP) (24). As a control, the promoter of DRG1 , a constitutive gene expressed at a level similar to that of EFG1 (25), was similarly cloned. Expression of yEGFP was measured following growth to post-exponential phase in rich medium at 37°C.…”

Section: Resultsmentioning

confidence: 99%

Variation in Candida albicans EFG1 Expression Enables Host-Dependent Changes in Colonizing Fungal Populations

Pierce

Kumamoto

2012

mBio

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ABSTRACTTo understand differences in host-Candida albicansinteractions that occur during colonization of healthy or compromised hosts, production of phenotypic variants and colonization of healthy or immunodeficient mice byC. albicanswere studied. We showed that activity of the transcription factor Efg1p exhibited cell-to-cell variability and identified Efg1p as a major regulator of colonization. InC. albicanspopulations colonizing the murine gastrointestinal tract, average expression ofEFG1differed depending on the immune status of the host. We propose that cellular heterogeneity in Efg1p activity allows theC. albicanscolonizing population to differ depending on the immune status of the host, because selective pressure from a healthy host alters the composition of the population. These data are the first demonstration that differences in host immune status are associated with differences in gene expression in colonizingC. albicanscells. Altered gene expression in organisms colonizing immunocompromised hosts may begin the transition ofC. albicansfrom a commensal to a pathogen.IMPORTANCEIn healthy people, the fungusCandida albicanscolonizes the gastrointestinal tract and other sites without producing obvious pathology. In an immunocompromised patient, the organism can cause serious disease. The demonstration that the expression and activity of theC. albicanstranscription factor Efg1p differs during colonization of healthy or immunocompromised mice shows that the organism adjusts its physiology when colonizing different hosts. Further, the effects of a healthy host on a heterogeneousC. albicanspopulation containing cells with different levels of Efg1p activity show that selective pressure in the host can change the makeup of the population, allowing the population to respond to host immune status. The ability to sense host status may be key to the ability ofC. albicansto colonize as a harmless commensal in some hosts but become a deadly pathogen in others.

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Section: Resultsmentioning

confidence: 99%

Variation in Candida albicans EFG1 Expression Enables Host-Dependent Changes in Colonizing Fungal Populations

Pierce

Kumamoto

2012

mBio

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114

130

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“…yEGFP- [ 30 ] expressing EFH1 + and efh1 null mutant strains were constructed by transforming RM1000 His + or the efh1 null mutant with pDRG-GFPS6, encoding yEGFP under control of the DRG1 promoter [ 47 ].…”

Section: Methodsmentioning

confidence: 99%

“…To construct pDRG-GFPS6, the DRG1 promoter region [ 47 ] was amplified with primers XC3 and XC4 and cloned onto plasmid pXC31, a vector containing BamHI, NsiI, SalI, and EcoRV sites upstream of a promoterless yEGFP gene that was fused to the 3′ UTR of ACT1 in pNUB1 (pNEB193 from New England Biolabs, with C. albicans URA3 [ 47 ]).…”

Section: Methodsmentioning

confidence: 99%

Self-Regulation of Candida albicans Population Size during GI Colonization

et al. 2007

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Interactions between colonizing commensal microorganisms and their hosts play important roles in health and disease. The opportunistic fungal pathogen Candida albicans is a common component of human intestinal flora. To gain insight into C. albicans colonization, genes expressed by fungi grown within a host were studied. The EFH1 gene, encoding a putative transcription factor, was highly expressed during growth of C. albicans in the intestinal tract. Counterintuitively, an efh1 null mutant exhibited increased colonization of the murine intestinal tract, a model of commensal colonization, whereas an EFH1 overexpressing strain exhibited reduced colonization of the intestinal tract and of the oral cavity of athymic mice, the latter situation modeling human mucosal candidiasis. When inoculated into the bloodstream of mice, both efh1 null and EFH1 overexpressing strains caused lethal infections. In contrast, other mutants are attenuated in virulence following intravenous inoculation but exhibited normal levels of intestinal colonization. Finally, although expression of several genes is dependent on transcription factor Efg1p during laboratory growth, Efg1p-independent expression of these genes was observed during growth within the murine intestinal tract. These results show that expression of EFH1 regulated the level of colonizing fungi, favoring commensalism as opposed to candidiasis. Also, different genes are required in different host niches and the pathway(s) that regulates gene expression during host colonization can differ from well-characterized pathways used during laboratory growth.

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“…Studies also suggest that DRG1 is associated with SCL/TAL1 in vivo and in vitro , which is an oncogenic transcription factor for hematopoietic development [8, 9]. DRG1 from Candida albicans can contribute to the control of invasive filamentation and DRG1 deletion delays the invasive disease in the host [10]. Among all tumors, DRG1 has been proposed as a oncogene in melanoma, a marker for CPT-11 resistance in human head and neck xenograft tumors, and related gene in the recurrence probability of colon cancer [11–13].…”

Section: Introductionmentioning

confidence: 99%

DRG1 is a potential oncogene in lung adenocarcinoma and promotes tumor progression via spindle checkpoint signaling regulation

Lü

et al. 2016

Oncotarget

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Developmentally regulated GTP binding protein 1 (DRG1), a member of the DRG family, plays important roles in regulating cell growth. However, the molecular basis of DRG1 in cell proliferation regulation and the relationship between DRG1 and tumor progression remain poorly understood. Here, we demonstrate that DRG1 is elevated in lung adenocarcinomas while weakly expressed in adjacent lung tissues. DRG1 knockdown causes growth inhibition of tumor cells by significantly increasing the proportion of cells in M phase. Overexpression of DRG1 leads to chromosome missegregation which is an important index for tumorigenesis. Interestingly, ectopic of DRG1 reduces taxol induced apoptosis of lung adenocarcinoma cells. Mechanistic analyses confirm that DRG1 localizes at mitotic spindles in dividing cells and binds to spindle checkpoint signaling proteins in vivo. These studies highlight the expanding role of DRG1 in tumorigenesis and reveal a mechanism of DRG1 in taxol resistance.

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A conserved G protein (Drg1p) plays a role in regulation of invasive filamentation in Candida albicans

Cited by 11 publications

References 27 publications

Variation in Candida albicans EFG1 Expression Enables Host-Dependent Changes in Colonizing Fungal Populations

Variation in Candida albicans EFG1 Expression Enables Host-Dependent Changes in Colonizing Fungal Populations

Self-Regulation of Candida albicans Population Size during GI Colonization

DRG1 is a potential oncogene in lung adenocarcinoma and promotes tumor progression via spindle checkpoint signaling regulation

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