Metal-Binding and Nuclease Activity of an Antimicrobial Peptide Analogue of the Salivary Histatin 5†

Biochemistry ◽  
2006 ◽  
Vol 45 (51) ◽  
pp. 15373-15383 ◽  
Author(s):  
Sonia Melino ◽  
Mariana Gallo ◽  
Edoardo Trotta ◽  
Francesca Mondello ◽  
Maurizio Paci ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Metal Binding ◽  
Nuclease Activity ◽  
Histatin 5 ◽  
Peptide Analogue

scholarly journals Adsorption behavior of antimicrobial peptide histatin 5 on PMMA

2006 ◽  
Vol 77B (1) ◽  
pp. 47-54 ◽  
Author(s):  
Masao Yoshinari ◽  
Tetsuo Kato ◽  
Kenichi Matsuzaka ◽  
Tohru Hayakawa ◽  
Takashi Inoue ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Adsorption Behavior ◽  
Histatin 5

scholarly journals The salivary, metal-binding peptide histatin-5 buffers extracellular copper availability

2022 ◽  
Author(s):  
Louisa Stewart ◽  
YoungJin Hong ◽  
Isabel Holmes ◽  
Samantha Firth ◽  
Jack Bolton ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Metal Binding ◽  
Group A Streptococcus ◽  
Negative Effects ◽  
Histatin 5 ◽  
High Affinity ◽  
Nutritional Immunity ◽  
Zn Uptake ◽  
Inducible Genes ◽  
Zn Availability

The family of human salivary histidine-rich peptides known as histatins bind zinc (Zn) and copper (Cu), but whether they contribute to nutritional immunity by influencing Zn and/or Cu availability has not been examined. We hypothesised that histatin-5 (Hst5) limits Zn availability (and promotes bacterial Zn starvation) and/or raises Cu availability (and promotes bacterial Cu poisoning). To test this hypothesis, Group A Streptococcus (GAS), which colonises the human oropharynx, was used as a model bacterium. Contrary to our hypothesis, Hst5 did not strongly influence Zn availability. This peptide did not induce expression of Zn uptake genes in GAS, nor did it suppress growth of an ΔadcAI mutant strain that is impaired in Zn uptake. Equilibrium competition measurements confirmed that Hst5 binds Zn weakly and does not compete with the high-affinity Zn uptake protein AdcAI for binding Zn. By contrast, Hst5 bound Cu with a high affinity and strongly influenced Cu availability. However, contrary to our hypothesis, Hst5 did not promote Cu toxicity. Instead, this peptide suppressed expression of Cu-inducible genes in GAS, stopped intracellular accumulation of Cu, and rescued growth of a ΔcopA mutant strain that is impaired in Cu efflux in the presence of added Cu. These findings led us to propose a new role for Hst5 and salivary histatins as major Cu buffers in saliva that reduce the potential negative effects of Cu exposure to microbes. We speculate that histatins promote oral and oropharyngeal health by contributing to microbial homeostasis in these host niches.

scholarly journals Systematic Peptide Engineering and Structural Characterization to Search for the Shortest Antimicrobial Peptide Analogue of Gaegurin 5

2004 ◽  
Vol 279 (15) ◽  
pp. 14784-14791 ◽  
Author(s):  
Hyung-Sik Won ◽  
Seo-Jeong Jung ◽  
Hyung Eun Kim ◽  
Min-Duk Seo ◽  
Bong-Jin Lee
Keyword(s):  
Antimicrobial Peptide ◽  
Structural Characterization ◽  
Peptide Analogue ◽  
Peptide Engineering

scholarly journals Association between Antimicrobial Peptide Histatin 5 Levels and Prevalence of Candida in Saliva of Patients with Down Syndrome

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 494
Author(s):  
Tomoko Komatsu ◽  
Kiyoko Watanabe ◽  
Nobushiro Hamada ◽  
Eva Helmerhorst ◽  
Frank Oppenheim ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Elderly Patients ◽  
Antimicrobial Peptide ◽  
Total Protein ◽  
The Other ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fungal Colonization ◽  
Candida Colonization ◽  
Histatin 5 ◽  
Oral Candida

There are no studies on Candida colonization and micropeptides of saliva in any patient. Therefore, we studied the effects of the salivary antimicrobial peptide histatin 5 on oral fungal colonization; subjects were subdivided into Down syndrome (D) and normal (N) groups by age: N-1 and D-1, age <20 years; N-2 and D-2, age >40 years. Histatin 5 concentration in saliva was measured by enzyme-linked immunosorbent assay. Oral Candida species were identified using CHROMagar Candida. Candida colonization was significantly enhanced in the D-1 and D-2 groups compared to the N-1 and N-2 groups. There was no predominant difference in salivary histatin 5 concentration between the D-1 and N-1 groups, but it was significantly lower in the D-2 group than in the N-2 group. Only in the N-2 group was there a correlation between the concentration of histatin 5 and total protein, while no correlation was found in the other groups. In elderly patients with Down syndrome, the decrease in histatin 5 shown in this study may lead to oral Candida colony formation. Therefore, the results of this study suggest that a deficiency of the antimicrobial peptide histatin 5 could possibly induce oral Candida infection in DS.

scholarly journals Role of CgTpo4 in Polyamine and Antimicrobial Peptide Resistance: Determining Virulence in Candida glabrata

2021 ◽  
Vol 22 (3) ◽  
pp. 1376
Author(s):  
Mafalda Cavalheiro ◽  
Daniela Romão ◽  
Rui Santos ◽  
Dalila Mil-Homens ◽  
Pedro Pais ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Candida Glabrata ◽  
Defense Mechanism ◽  
Galleria Mellonella ◽  
Antifungal Drugs ◽  
Yeast Cells ◽  
Infection Model ◽  
Histatin 5 ◽  
Host Defense Mechanism ◽  
Antimicrobial Peptide Resistance

Candida glabrata is an emerging fungal pathogen whose success depends on its ability to resist antifungal drugs but also to thrive against host defenses. In this study, the predicted multidrug transporter CgTpo4 (encoded by ORF CAGL0L10912g) is described as a new determinant of virulence in C. glabrata, using the infection model Galleria mellonella. The CgTPO4 gene was found to be required for the C. glabrata ability to kill G. mellonella. The transporter encoded by this gene is also necessary for antimicrobial peptide (AMP) resistance, specifically against histatin-5. Interestingly, G. mellonella’s AMP expression was found to be strongly activated in response to C. glabrata infection, suggesting AMPs are a key antifungal defense. CgTpo4 was also found to be a plasma membrane exporter of polyamines, especially spermidine, suggesting that CgTpo4 is able to export polyamines and AMPs, thus conferring resistance to both stress agents. Altogether, this study presents the polyamine exporter CgTpo4 as a determinant of C. glabrata virulence, which acts by protecting the yeast cells from the overexpression of AMPs, deployed as a host defense mechanism.

scholarly journals The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance

2020 ◽  
Vol 21 (7) ◽  
pp. 2654 ◽  
Author(s):  
Kuang-Ting Cheng ◽  
Chih-Lung Wu ◽  
Bak-Sau Yip ◽  
Ya-Han Chih ◽  
Kuang-Li Peng ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Antimicrobial Peptide ◽  
Oral Candidiasis ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Salivary Protein ◽  
Histatin 5 ◽  
C Terminus

In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with Candida albicans or its degradation by Candida-secreted proteases that contribute to the fungi’s resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living Candida albicans cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications.

scholarly journals How Does It Kill?: Understanding the Candidacidal Mechanism of Salivary Histatin 5

2014 ◽  
Vol 13 (8) ◽  
pp. 958-964 ◽  
Author(s):  
Sumant Puri ◽  
Mira Edgerton
Keyword(s):  
Metal Binding ◽  
Oral Candidiasis ◽  
Critical Evaluation ◽  
Dependent Manner ◽  
Content Type ◽  
Histatin 5 ◽  
Mitochondrial Functions ◽  
Ultimate Cause ◽  
Ion Imbalance ◽  
Energy Dependent

ABSTRACTHistatins are salivary cationic peptides that provide the first line of defense against oral candidiasis caused byCandida albicans. This minireview presents a critical evaluation of our knowledge of the candidacidal mechanism of histatin 5 (Hst 5). Hst 5 is the most potent among all histatin family members with regard to its antifungal activity. The mode of action of Hst 5 has been a subject of intense debate. Unlike other classical host innate immune proteins, pore formation or membrane lysis by Hst 5 has largely been disproven, and it is now known that all targets of Hst 5 are intracellular. Hst 5 bindsC. albicanscell wall proteins (Ssa1/2) and glycans and is taken up by the cells through fungal polyamine transporters in an energy-dependent manner. Once inside the fungal cells, Hst 5 may affect mitochondrial functions and cause oxidative stress; however, the ultimate cause of cell death is by volume dysregulation and ion imbalance triggered by osmotic stress. Besides these diverse targets, a novel mechanism based on the metal binding abilities of Hst 5 is discussed. Finally, translational approaches for Hst 5, based on peptide design and synergy with other known drugs, are considered a step forward for bench-to-bed application of Hst 5.

Serial Expression and Activity Analysis of LNK-16: A Bovine Antimicrobial Peptide Analogue

2014 ◽  
Vol 33 (4) ◽  
pp. 309-312 ◽  
Author(s):  
Yanzhao Xu ◽  
Qing Wang ◽  
Bolin Hang ◽  
Dengfeng Fu ◽  
Tiantian Shang ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Activity Analysis ◽  
Peptide Analogue ◽  
Expression And Activity
Sign in / Sign up

Export Citation Format

Share Document