scholarly journals Zinc Binding by Histatin 5 Promotes Fungicidal Membrane Disruption in C. albicans and C. glabrata

2020 ◽  
Vol 6 (3) ◽  
pp. 124 ◽  
Author(s):  
Hannah L. Norris ◽  
Rohitashw Kumar ◽  
Chih Yean Ong ◽  
Ding Xu ◽  
Mira Edgerton
Keyword(s):  
High Performance ◽  
Opportunistic Pathogen ◽  
Human Saliva ◽  
Membrane Disruption ◽  
Initial Surface ◽  
Surface Binding ◽  
Histatin 5 ◽  
Peptide Assembly ◽  
Cell Association ◽  
Exciting Potential

Histatin 5 (Hst 5) is an antimicrobial peptide produced in human saliva with antifungal activity for opportunistic pathogen Candida albicans. Hst 5 binds to multiple cations including dimerization-inducing zinc (Zn2+), although the function of this capability is incompletely understood. Hst 5 is taken up by C. albicans and acts on intracellular targets under metal-free conditions; however, Zn2+ is abundant in saliva and may functionally affect Hst 5. We hypothesized that Zn2+ binding would induce membrane-disrupting pores through dimerization. Through the use of Hst 5 and two derivatives, P113 (AA 4-15 of Hst 5) and Hst 5ΔMB (AA 1-3 and 15-19 mutated to Glu), we determined that Zn2+ significantly increases killing activity of Hst 5 and P113 for both C. albicans and Candida glabrata. Cell association assays determined that Zn2+ did not impact initial surface binding by the peptides, but Zn2+ did decrease cell association due to active peptide uptake. ATP efflux assays with Zn2+ suggested rapid membrane permeabilization by Hst 5 and P113 and that Zn2+ affinity correlates to higher membrane disruption ability. High-performance liquid chromatography (HPLC) showed that the higher relative Zn2+ affinity of Hst 5 likely promotes dimerization. Together, these results suggest peptide assembly into fungicidal pore structures in the presence of Zn2+, representing a novel mechanism of action that has exciting potential to expand the list of Hst 5-susceptible pathogens.

Analysis of caffeine and paraxanthine in human saliva with ultra-high-performance liquid chromatography for CYP1A2 phenotyping

2015 ◽  
Vol 995-996 ◽  
pp. 70-73 ◽  
Author(s):  
Nan Yeun Jordan ◽  
Jolet Y. Mimpen ◽  
Willie J.M. van den Bogaard ◽  
Frits M. Flesch ◽  
Michiel H.M. van de Meent ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Human Saliva

scholarly journals Bonding evolution with sintering temperature in low alloyed steels with chromium

2009 ◽  
Vol 41 (2) ◽  
pp. 161-173 ◽  
Author(s):  
L. Fuentes-Pacheco ◽  
M. Campos
Keyword(s):  
Carbothermic Reduction ◽  
High Performance ◽  
Sintering Temperature ◽  
Surface Oxide ◽  
Dew Point ◽  
Processing Route ◽  
Initial Surface ◽  
Sintered Steels ◽  
Controlling Mechanism ◽  
Die Compaction

At present, high performance PM steels for automotive applications follow a processing route that comprises die compaction of water-atomized powder, followed by sintering and secondary treatments, and finishing operations. This study examines Cr-alloyed sintered steels with two level of alloying. In chromium-alloyed steels, the surface oxide on the powder is of critical importance for developing the bonding between the particles during sintering. Reduction of this oxide depends mainly on three factors: temperature, dew point of the atmosphere, and carbothermic reduction provided by the added graphite. The transformation of the initial surface oxide evolves sequence as temperature increases during sintering, depending on the oxide composition. Carbothermic reduction is supposed to be the controlling mechanism, even when sintering in hydrogen-containing atmospheres. The effect of carbothermic reduction can be monitored by investigating the behavior of the specimens under tensile testing, and studying the resultant fracture surfaces.

scholarly journals Screening Mold Colonies by Using Two Toxicity Assays Revealed Indoor Strains of Aspergillus calidoustus Producing Ophiobolins G and K

Toxins ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 683 ◽  
Author(s):  
Marja Johanna Salo ◽  
Tamás Marik ◽  
Ottó Bencsik ◽  
Raimo Mikkola ◽  
László Kredics ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Proliferation ◽  
Sperm Motility ◽  
High Performance ◽  
Biological Activities ◽  
Membrane Integrity ◽  
Opportunistic Pathogen ◽  
Mass Spectrometry Data ◽  
Toxic Substances ◽  
Boar Sperm

The occurrence and toxin production of the opportunistic pathogen Aspergillus calidoustus in Finnish buildings is not well documented in the literature. We tracked and identified four A. calidoustus colonies cultivated from indoor settled dusts and revealed the biological activities of crude biomass extracts. The toxic substances were identified as 6-epi-ophiobolin K, ophiobolin K, and ophiobolin G by high-performance liquid chromatography–mass spectrometry (HPLC-MS) based on chromatographic and mass spectrometry data (MS and MS/MS) on the crude extract of A. calidoustus strain MH34. A total of 29 fungal colonies collected from settled dust in an office room reported for indoor-air-related illnesses were screened for toxins that inhibited boar sperm motility in the BSMI (boar sperm motility inhibiting) assay and cell proliferation in the ICP (inhibition of cell proliferation) assays with PK-15 cells. Out of the 27 colonies tested as toxic, 12 colonies exhibiting conidiophores representative of the genera Chaetomium, Penicillium, and Paecilomyces were excluded from the study, while 13 colonies exhibited Aspergillus-like conidiophores. Biomass suspensions of these colonies were divided into two categories: Category 1 colonies (n = 4), toxic in the BSMI assay and the ICP assays, emitted blue fluorescence and grew at 37 °C; Category 2 colonies (n = 9), only toxic in the ICP assay, emitted orange fluorescence and exhibited limited or no growth at 37 °C. Colonies in Category 1 were pure-cultured, and the strains were named as MH4, MH21, MH34, MH36. Strain MH34 was identified as A. calidoustus by the internal transcribed spacer (ITS) sequences. Ethanol-soluble dry substances extracted from the biomass of the pure cultures exhibited a toxicological profile in the BSMI assay, SMID (sperm membrane integrity damage) assay, and ICP assay similar to that exhibited by pure ophiobolin A. Overall, the viable conidia of A. calidoustus in indoor settled dusts deserve attention when potentially hazardous mold species are monitored.

Salivary Histatin 5 and its Similarities to the Other Antimicrobial Proteins in Human Saliva

2000 ◽  
Vol 14 (1) ◽  
pp. 16-21 ◽  
Author(s):  
M. Edgerton ◽  
S.E. Koshlukova
Keyword(s):  
Antimicrobial Activity ◽  
Oral Cavity ◽  
Human Saliva ◽  
Oral Bacteria ◽  
Defense System ◽  
Antimicrobial Proteins ◽  
Cationic Proteins ◽  
Histatin 5 ◽  
Host Defense System ◽  
Bacteria And Fungi

Non-immune salivary proteins-including lactoperoxidase, lysozyme, lactoferrin, and histatins-are key components of the innate host defense system in the oral cavity. Many antimicrobial proteins contain multiple functional domains, with the result that one protein may have more than one mechanism of antimicrobial activity. These domains may be separated by proteolytic cleavage, creating smaller proteins with functional antimicrobial activity in saliva as described for lysozyme, lactoferrin, and histatins. These small cationic proteins then exert cytotoxic activity to oral bacteria and fungi. Salivary histatin 5 initiates killing of C. albicans through binding to yeast membrane proteins and non-lytic release of cellular ATP. Extracellular ATP may then activate fungal ATP receptors to induce ultimate cell death. This mechanism for fungal cytotoxicity may be shared by other antimicrobial cationic proteins. Microbicidal domains of salivary and host innate proteins should be considered as potential therapeutic agents in the oral cavity.

The determination of bradykinin in human saliva by high-performance liquid chromatography with UV detection

1986 ◽  
Vol 4 (4) ◽  
pp. 529-532 ◽  
Author(s):  
Hisashi Omori ◽  
Yushin Takahashi ◽  
Toshiro Sakakibara ◽  
Sumio Ota ◽  
Tadashi Nakashizuka
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Human Saliva ◽  
Uv Detection

scholarly journals Circadian Rhythms of Histatin 1, Histatin 3, Histatin 5, Statherin and Uric Acid in Whole Human Saliva Secretion

2002 ◽  
Vol 33 (2) ◽  
pp. 213-222 ◽  
Author(s):  
M. Castagnola ◽  
T. Cabras ◽  
G. Denotti ◽  
M.B. Fadda ◽  
G. Gambarini ◽  
...  
Keyword(s):  
Uric Acid ◽  
Circadian Rhythms ◽  
Human Saliva ◽  
Histatin 5 ◽  
Saliva Secretion
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