Human Salivary Histatin 5 Causes Disordered Volume Regulation and Cell Cycle Arrest in<i>Candida albicans</i>

Baev, Didi; Li, Xuewei S.; Dong, Jin; Keng, Peter C.; Edgerton, Mira

doi:10.1128/iai.70.9.4777-4784.2002

Cited by 66 publications

(54 citation statements)

References 33 publications

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“…Our current working hypothesis to account for these facts is that the structural path for Cl Ϫ through Trk1p is distorted by Hst 5 binding so that it permits the efflux of larger anions, such as ATP, but DIDS "seals" the channel against Hst 5 action. Trk1p-dependent loss of ATP and other large anions initiates cellular shrinkage and eventual cell cycle arrest that are thus blocked by DIDS (16). Moreover, as evidenced in Fig.…”

Section: Mediation Of Hstmentioning

confidence: 80%

“…These obvious membrane effects are accompanied by a rapid and irreversible loss of cell volume and ultimately by cell cycle arrest (16). However, all such toxic effects, including cell death, can be attenuated or blocked by a curious range of agents: by protonophores such as CCCP and DNP (8,17,18), by elevated extracellular calcium (19,20), by elevated external potassium (9,11), and (very surprisingly) by well known anion channel inhibitors such as niflumic acid, 5-nitro-2-(3-phenylpropylamino)benzoic acid, and DIDS (16).…”

mentioning

confidence: 99%

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The TRK1 Potassium Transporter Is the Critical Effector for Killing of Candida albicans by the Cationic Protein, Histatin 5

Baev

Rivetta

Vylkova

et al. 2004

Journal of Biological Chemistry

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Section: Mediation Of Hstmentioning

confidence: 80%

mentioning

confidence: 99%

The TRK1 Potassium Transporter Is the Critical Effector for Killing of Candida albicans by the Cationic Protein, Histatin 5

Baev

Rivetta

Vylkova

et al. 2004

Journal of Biological Chemistry

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“…In a RHE model, the expression of ALS1, ALS2, ALS3, ALS4, ALS5, and ALS9 was present over time (12,24,36, and 48 h) for each of the three inoculum concentrations tested (RT-PCR [130]). For both ALS3 and ALS5, one replicate among all the analyses fell below the detection limit.…”

Section: Adhesinsmentioning

confidence: 99%

Candida albicansCell Wall Proteins

Chaffin

2008

Microbiol Mol Biol Rev

424

404

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SUMMARY The Candida albicans cell wall maintains the structural integrity of the organism in addtion to providing a physical contact interface with the environment. The major components of the cell wall are fibrillar polysaccharides and proteins. The proteins of the cell wall are the focus of this review. Three classes of proteins are present in the candidal cell wall. One group of proteins attach to the cell wall via a glycophosphatidylinositol remnant or by an alkali-labile linkage. A second group of proteins with N-terminal signal sequences but no covalent attachment sequences are secreted by the classical secretory pathway. These proteins may end up in the cell wall or in the extracellular space. The third group of proteins lack a secretory signal, and the pathway(s) by which they become associated with the surface is unknown. Potential constituents of the first two classes have been predicted from analysis of genome sequences. Experimental analyses have identified members of all three classes. Some members of each class selected for consideration of confirmed or proposed function, phenotypic analysis of a mutant, and regulation by growth conditions and transcription factors are discussed in more detail.

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“…ROS could disrupt the cell organelle structure or function, or induce lethal DNA damage. Histatin 5 has also been shown to disrupt the cell cycle in C. albicans, halting cells in the G1 phase with a concomitant effect on the regulation of cell volume homoeostasis, which is correlated with ATP loss (Baev et al 2002).…”

Section: Mode Of Action Of Histatinsmentioning

confidence: 99%

Histatins: antimicrobial peptides with therapeutic potential

Kavanagh

Dowd

2004

Journal of Pharmacy and Pharmacology

166

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Histatins are a group of antimicrobial peptides, found in the saliva of man and some higher primates, which possess antifungal properties. Histatins bind to a receptor on the fungal cell membrane and enter the cytoplasm where they target the mitochondrion. They induce the non-lytic loss of ATP from actively respiring cells, which can induce cell death. In addition, they have been shown to disrupt the cell cycle and lead to the generation of reactive oxygen species. Their mode of action is distinct from those exhibited by the conventional azole and polyene drugs, hence histatins may have applications in controlling drug-resistant fungal infections. The possibility of utilising histatins for the control of fungal infections of the oral cavity is being actively pursued with the antifungal properties of topical histatin preparations and histatin-impregnated denture acrylic being evaluated. Initial clinical studies are encouraging, having demonstrated the safety and efficacy of histatin preparations in blocking the adherence of the yeast Candida albicans to denture acrylic, retarding plaque formation and reducing the severity of gingivitis. Histatins may represent a new generation of antimicrobial compounds for the treatment of oral fungal infections and have the advantage, compared with conventional antifungal agents, of being a normal component of human saliva with no apparent adverse effects on host tissues and having a mode of action distinct to azole and polyene antifungals.

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Human Salivary Histatin 5 Causes Disordered Volume Regulation and Cell Cycle Arrest inCandida albicans

Cited by 66 publications

References 33 publications

The TRK1 Potassium Transporter Is the Critical Effector for Killing of Candida albicans by the Cationic Protein, Histatin 5

The TRK1 Potassium Transporter Is the Critical Effector for Killing of Candida albicans by the Cationic Protein, Histatin 5

Candida albicansCell Wall Proteins

Histatins: antimicrobial peptides with therapeutic potential

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