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The SPS amino acid sensor mediates nutrient acquisition and immune evasion in Candida albicans.

ABSTRACT: Candida albicans is well adapted to its host and is able to sense and respond to the nutrients available within. We have shown that C.?albicans avidly utilizes amino acids as a carbon source, which allows this opportunistic pathogen to neutralize acidic environments, including the macrophage phagosome. The transcription factor Stp2 is a key regulator of this phenomenon, and we sought to understand the mechanism of activation of Stp2, focusing on the SPS sensor system previously characterized for its role in nitrogen acquisition. We generated deletion mutants of the three components, SSY1, PTR3 and SSY5 and demonstrated that these strains utilize amino acids poorly as carbon source, cannot neutralize the medium in response to these nutrients, and have reduced ammonia release. Exogenous amino acids rapidly induce proteolytic processing of Stp2 and nuclear translocation in an SPS-dependent manner. A truncated version of Stp2, lacking the amino terminal nuclear exclusion domain, could suppress the growth and pH neutralization defects of the SPS mutants. We showed that the SPS system is required for normal resistance of C.?albicans to macrophages and that mutants defective in this system reside in more acidic phagosomes compared with wild type cells; however, a more equivocal contribution was observed in the murine model of disseminated candidiasis. Taken together, these results indicate that the SPS system is activated under carbon starvation conditions resembling host environments, regulating Stp2 functions necessary for amino acid catabolism and normal interactions with innate immune cells.

SUBMITTER: Miramon P

PROVIDER: S-EPMC5501722 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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The SPS amino acid sensor mediates nutrient acquisition and immune evasion in Candida albicans.

Miramón Pedro P Lorenz Michael C MC

Cellular microbiology 20160527 11

Candida albicans is well adapted to its host and is able to sense and respond to the nutrients available within. We have shown that C. albicans avidly utilizes amino acids as a carbon source, which allows this opportunistic pathogen to neutralize acidic environments, including the macrophage phagosome. The transcription factor Stp2 is a key regulator of this phenomenon, and we sought to understand the mechanism of activation of Stp2, focusing on the SPS sensor system previously characterized for ...[more]

PMID: 27060451

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Project description:Oropharyngeal candidiasis is an opportunistic infection considered to be a harbinger of AIDS. The etiologic agent Candida albicans is a fungal species commonly colonizing human mucosal surfaces. However, under conditions of immune dysfunction, colonizing C. albicans can become an opportunistic pathogen causing superficial or even life-threatening infections. The reasons behind this transition, however, are not clear. In the oral cavity, salivary antimicrobial peptides are considered to be an important part of the host innate defense system in the prevention of microbial colonization. Histatin-5 specifically has exhibited potent activity against C. albicans. Our previous studies have shown histatin-5 levels to be significantly reduced in the saliva of HIV+ individuals, indicating an important role for histatin-5 in keeping C. albicans in its commensal stage. The versatility in the pathogenic potential of C. albicans is the result of its ability to adapt through the regulation of virulence determinants, most notably of which are proteolytic enzymes (Saps), involved in tissue degradation. In this study, we show that C. albicans cells efficiently and rapidly degrade histatin-5, resulting in loss of its anti-candidal potency. In addition, we demonstrate that this cellular activity is due to proteolysis by a member of the secreted aspartic proteases (Sap) family involved in C. albicans pathogenesis. Specifically, the proteolysis was attributed to Sap9, in turn identifying histatin-5 as the first host-specific substrate for that isoenzyme. These findings demonstrate for the first time the ability of a specific C. albicans enzyme to degrade and deactivate a host antimicrobial peptide involved in the protection of the oral mucosa against C. albicans, thereby providing new insights into the factors directing the transition of C. albicans from commensal to pathogen, with important clinical implications for alternative therapy. This report characterizes the first defined mechanism behind the enhanced susceptibility of HIV+ individuals to oral candidiasis since the emergence of HIV.

Dataset Information

The SPS amino acid sensor mediates nutrient acquisition and immune evasion in Candida albicans.

Publications

The SPS amino acid sensor mediates nutrient acquisition and immune evasion in Candida albicans.

Similar Datasets

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