A Peptide Found in Human Serum, Derived from the C-Terminus of Albumin, Shows Antifungal Activity In Vitro and In Vivo.

Tecla Ciociola,Pier Paolo Zanello,Serena Galati,Laura Giovati,Tiziana D'Adda,Stefania Conti,Walter Magliani

doi:10.3390/microorganisms8101627

Tecla Ciociola, Pier Paolo Zanello + Show 5 more

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https://doi.org/10.3390/microorganisms8101627

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Journal: Microorganisms	Publication Date: Oct 21, 2020
Citations: 8	License type: CC BY 4.0

Affiliation: University of Parma

Abstract

The growing problem of antimicrobial resistance highlights the need for alternative strategies to combat infections. From this perspective, there is a considerable interest in natural molecules obtained from different sources, which are shown to be active against microorganisms, either alone or in association with conventional drugs. In this paper, peptides with the same sequence of fragments, found in human serum, derived from physiological proteins, were evaluated for their antifungal activity. A 13-residue peptide, representing the 597–609 fragment within the albumin C-terminus, was proved to exert a fungicidal activity in vitro against pathogenic yeasts and a therapeutic effect in vivo in the experimental model of candidal infection in Galleria mellonella. Studies by confocal microscopy and transmission and scanning electron microscopy demonstrated that the peptide penetrates and accumulates in Candida albicans cells, causing gross morphological alterations in cellular structure. These findings add albumin to the group of proteins, which already includes hemoglobin and antibodies, that could give rise to cryptic antimicrobial fragments, and could suggest their role in anti-infective homeostasis. The study of bioactive fragments from serum proteins could open interesting perspectives for the development of new antimicrobial molecules derived by natural sources.

Highlights

Despite the recent extraordinary advances in medical fields leading to a significant increase in life expectancy, especially in rich and industrialized countries, paradoxically these same progresses have been linked to an increased risk of the emergence or re-emergence of infectious diseases
All peptides were preliminarily tested at the concentration of 100 μg/mL vs. the reference strain C. albicans SC5314
The peptides that exhibited fungicidal activity in the preliminary assay were subsequently tested at scalar dilutions to determine the half maximal effective concentration (EC50) values against the selected fungal strains C. albicans CA-6, SA40, AIDS68, and UM4, and C. glabrata OMNI32 [13]

Summary

Introduction

Despite the recent extraordinary advances in medical fields leading to a significant increase in life expectancy, especially in rich and industrialized countries, paradoxically these same progresses have been linked to an increased risk of the emergence or re-emergence of infectious diseases. An ageing population contributes to an increased risk of infections, even in the absence of other co-morbidities. As stated by the World Health Organization, antimicrobial resistance poses a huge threat to human health. The direct consequences of infection with resistant microorganisms include longer illnesses, increased mortality, prolonged stays in hospital, loss of protection for patients undergoing surgery and other medical procedures, as well as a significant growth in healthcare costs [1]. To cope with the problems posed by the spread of resistant microbial strains and to treat immunocompromised subjects more adequately, it is increasingly urgent to develop new selective and safe therapeutic agents, with mechanisms of action possibly different from those of the antimicrobials currently in use

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