Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis

Ikonomova, Svetlana P.; Moghaddam-Taaheri, Parisa; Wang, Yan; Doolin, Mary T.; Stroka, Kimberly M.; Hube, Bernhard; Karlsson, Amy J.

doi:10.1002/pro.3767

Cited by 22 publications

(8 citation statements)

References 37 publications

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“…Ikonomova et al proposed the replacement of two lysines (positions 11 and 17) for two arginines in the histatin-5 sequence. This modification increased the antifungal activity and provided resistance to C. albicans proteolytic cleavage [116,117]. The same result was observed by Jephthah et al when producing a hybrid peptide of histatin-5 and spermidine.…”

Section: Histatins and Their Role In The Antifungal Treatmentsupporting

confidence: 69%

Bio- and Nanotechnology as the Key for Clinical Application of Salivary Peptide Histatin: A Necessary Advance

2020

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Candida albicans is a common microorganism of human’s microbiota and can be easily found in both respiratory and gastrointestinal tracts as well as in the genitourinary tract. Approximately 30% of people will be infected by C. albicans during their lifetime. Due to its easy adaptation, this microorganism started to present high resistance to antifungal agents which is associated with their indiscriminate use. There are several reports of adaptive mechanisms that this species can present. Some of them are intrinsic alteration in drug targets, secretion of extracellular enzymes to promote host protein degradation and efflux receptors that lead to a diminished action of common antifungal and host’s innate immune response. The current review aims to bring promising alternatives for the treatment of candidiasis caused mainly by C. albicans. One of these alternatives is the use of antifungal peptides (AFPs) from the Histatin family, like histatin‐5. Besides that, our focus is to show how nanotechnology can allow the application of these peptides for treatment of this microorganism. In addition, our intention is to show the importance of nanoparticles (NPs) for this purpose, which may be essential in the near future.

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Section: Histatins and Their Role In The Antifungal Treatmentsupporting

confidence: 69%

Bio- and Nanotechnology as the Key for Clinical Application of Salivary Peptide Histatin: A Necessary Advance

2020

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“…It is worth noting that, while total levels of intact, full-length Hst5 and other major histatins in fresh salivary gland secretions are relatively high (up to 50 μM) [10], steady-state levels in whole saliva are low [10], a consequence of rapid peptide degradation by unidentified salivary proteases and proteases from resident oral microbes [76,77]. Nearly fifty distinct histatin-derived peptide fragments have been identified [33,78].…”

Section: Discussionmentioning

confidence: 99%

“…While total levels of intact, full-length Hst5 and major histatins in fresh salivary gland secretions are high (up to 50 μM) 9 , steady-state levels in whole saliva are low 9 as a consequence of peptide degradation by unidentified salivary proteases and proteases from resident oral microbes 78,79 .…”

Section: Discussionmentioning

confidence: 99%

The role of metal binding in the function of the human salivary antimicrobial peptide histatin-5

Stewart

Hong

Holmes

et al. 2022

Preprint

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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.

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“…Modifications of histatin-5 have been analyzed, and a single amino acid residue change was enough to confer histatin-5 resistance to the proteolytic degradation by Saps of C. albicans . While K17R substitution improved the proteolytic resistance, K11R variation boosted the antifungal activity of histatin-5 [ 147 ]. Therefore, the combination of both changes in a single molecule, K11R-K17R, results in a peptide with both improvements.…”

Section: Antimicrobial Peptides From Humansmentioning

confidence: 99%

Antimicrobial Peptides with Anti-Candida Activity

Perez-Rodriguez

Eraso

Quindós

et al. 2022

IJMS

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Mycoses are accountable for millions of infections yearly worldwide. Invasive candidiasis is the most usual, presenting a high morbidity and mortality. Candida albicans remains the prevalent etiologic agent, but the incidence of other species such as Candida parapsilosis, Candida glabrata and Candida auris keeps increasing. These pathogens frequently show a reduced susceptibility to commonly used antifungal drugs, including polyenes, triazoles and echinocandins, and the incidence of emerging multi-drug-resistant strains of these species continues to increase. Therefore, the need to search for new molecules that target these pathogenic species in a different manner is now more urgent than ever. Nature is an almost endless source of interesting new molecules that could meet this need. Among these molecules, antimicrobial peptides, present in different sources in nature, possess some advantages over conventional antifungal agents, even with their own drawbacks, and are considered as a promising pharmacological option against a wide range of microbial infections. In this review, we describe 20 antimicrobial peptides from different origins that possess an activity against Candida.

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Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis

Abstract: This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 22 publications

References 37 publications

Bio- and Nanotechnology as the Key for Clinical Application of Salivary Peptide Histatin: A Necessary Advance

Bio- and Nanotechnology as the Key for Clinical Application of Salivary Peptide Histatin: A Necessary Advance

The role of metal binding in the function of the human salivary antimicrobial peptide histatin-5

Antimicrobial Peptides with Anti-Candida Activity

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