Thermodynamics of an antimicrobial peptide binding to different bacterial ribosomes

The emergence of drug resistance to Candida albicans is problematic in the clinical setting. Therefore, developing new antifungal drugs is in high demand. Our previous work indicated that the antimicrobial peptide P-113Tri exhibited higher antifungal activity against planktonic cells, biofilm cells, and clinical isolates of Candida species compared to its parental peptide P-113. In this study, we further investigated the difference between these two peptides in their mechanisms against C. albicans. Microscopic examination showed that P-113 rapidly gained access to C. albicans cells. However, most of the P-113Tri remained on the cell surface. Moreover, using a range of cell wall-defective mutants and competition assays, the results indicated that phosphomannan and N-linked mannan in the cell wall are important for peptide binding to C. albicans cells. Furthermore, the addition of exogenous phosphosugars reduced the efficacy of the peptide, suggesting that negatively charged phosphosugars also contributed to the peptide binding to the cell wall polysaccharides. Finally, using a glycan array, P-113Tri, but not P-113, can bind to other glycans commonly present on other microbial and mammalian cells. Together, these results suggest that P-113 and P-113Tri have fundamental differences in their interaction with C. albicans and candidacidal activities.

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A Periplasmic Antimicrobial Peptide-Binding Protein Is Required for Stress Survival in Vibrio cholerae

Frontiers in Microbiology ◽

10.3389/fmicb.2019.00161 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 3

Author(s):

Jessica Saul-McBeth ◽

Jyl S. Matson

Keyword(s):

Antimicrobial Peptide ◽

Vibrio Cholerae ◽

Binding Protein ◽

Peptide Binding ◽

Stress Survival

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Membrane Thinning Due to Antimicrobial Peptide Binding: An Atomic Force Microscopy Study of MSI-78 in Lipid Bilayers

Biophysical Journal ◽

10.1529/biophysj.105.062596 ◽

2005 ◽

Vol 89 (6) ◽

pp. 4043-4050 ◽

Cited By ~ 147

Author(s):

Almut Mecke ◽

Dong-Kuk Lee ◽

Ayyalusamy Ramamoorthy ◽

Bradford G. Orr ◽

Mark M. Banaszak Holl

Keyword(s):

Atomic Force Microscopy ◽

Antimicrobial Peptide ◽

Lipid Bilayers ◽

Peptide Binding ◽

Microscopy Study ◽

Atomic Force Microscopy Study ◽

Force Microscopy ◽

Atomic Force ◽

Membrane Thinning

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Loss of mannosylphosphate from Candida albicans cell wall proteins results in enhanced resistance to the inhibitory effect of a cationic antimicrobial peptide via reduced peptide binding to the cell surface

Microbiology ◽

10.1099/mic.0.026120-0 ◽

2009 ◽

Vol 155 (4) ◽

pp. 1058-1070 ◽

Cited By ~ 39

Author(s):

Mark Harris ◽

Héctor M. Mora-Montes ◽

Neil A. R. Gow ◽

Peter J. Coote

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Cell Surface ◽

Antimicrobial Peptide ◽

Yeast Cell ◽

Peptide Binding ◽

Transient Event ◽

Glucosamine Hydrochloride ◽

Outermost Layer ◽

Enhanced Resistance

The outermost layer of the Candida albicans cell wall is enriched with mannosylated glycoproteins. We have used a range of isogenic glycosylation mutants of C. albicans, which are defective to varying degrees in cell wall protein mannosylation, to investigate the role of the outermost layer of the yeast cell wall in mediating the fungicidal action of the cationic, α-helical antimicrobial peptide dermaseptin S3(1-16) [DsS3(1-16)]. The degree of phosphomannan loss, and concomitant reduction in surface negative charge, from the series of glycosylation mutants correlated with reduced levels of peptide binding to the cells. In turn, the reduced peptide binding correlated with enhanced resistance to DsS3(1-16). To ascertain whether DsS3(1-16) binds to negatively charged phosphate, we studied the effect of exogenous glucosamine 6-phosphate, and glucosamine hydrochloride as a negative control, on the antifungal efficacy of DsS3(1-16). Glucosamine 6-phosphate retarded the efficacy of DsS3(1-16), and this was attributed to the presence of phosphate, because addition of identical concentrations of glucosamine hydrochloride had little detrimental effect on peptide efficacy. Fluorescence microscopy with DsS3(1-16) tagged with fluorescein revealed that the peptide binds to the outer surface of the yeast cell, supporting our previous conclusion that the presence of exterior phosphomannan is a major determinant of the antifungal potency of DsS3(1-16). The binding of the peptide to the cell surface was a transient event that was followed by apparent localization of DsS3(1-16) in the vacuole or dissemination throughout the entire cytosol. The presence of glucosamine 6-phosphate clearly reduced the proportion of cells in the population that showed complete cytosolic staining, implying that the binding and entry of the peptide into the cytosol is significantly reduced due to the exogenous phosphate sequestering the peptide and reducing the amount of peptide able to bind to the surface phosphomannan. In conclusion, we present evidence that an antimicrobial peptide, similar to those employed by cells of the human immune system, has evolved to recognize molecular patterns on the surface of pathogens in order to maximize efficacy.

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