scholarly journals Lactoferrin-Derived Peptide Lactofungin Is Potently Synergistic with Amphotericin B

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Kenya E. Fernandes ◽  
Richard J. Payne ◽  
Dee A. Carter

ABSTRACT Lactoferrin (LF) is an iron-binding glycoprotein with broad-spectrum antimicrobial activity. Previously, we discovered that LF synergistically enhanced the antifungal efficacy of amphotericin B (AMB) across a variety of yeast species and subsequently hypothesized that this synergy was enhanced by the presence of small peptides derived from the whole LF molecule. In this study, LF was digested with pepsin under a range of conditions. The resulting hydrolysates exhibited enhanced synergy with AMB compared to its synergy with undigested LF. Samples were analyzed using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, and 14 peptides were identified. The sequences of these peptides were predicted by matching their molecular weights to those of a virtual digest with pepsin. The relative intensities of predicted peptides in each hydrolysate were compared with the activity of the hydrolysate, and the structural and physicochemical properties of the peptides were assessed. From this, a 30-residue peptide was selected for synthesis and dubbed lactofungin (LFG). Pure LFG was highly synergistic with AMB, outperforming native LF in all fungal species tested. With potential for further structural and chemical improvements, LFG is an excellent lead for development as an antifungal adjuvant.

2021 ◽  
Vol 3 (11) ◽  
Author(s):  
Vhudzani Tshisevhe ◽  
Barend Mitton ◽  
Lebogang Skosana

Geotrichosis is a world-wide mycosis caused by Geotrichum species. We report a rare case of an invasive cutaneous infection by Geotrichum klebahnii in a female patient with undiagnosed diabetes mellitus. The patient presented with right facial swelling not responding to antibiotics and could not recall trauma to the site of the lesion. Histological examination showed fungal hyphae invading salivary glands and bony tissues, and G. klebahnii was isolated from the culture of biopsy material. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS) confirmed the fungal species. Broth microdilution showed low minimum inhibitory concentrations (MICs) for itraconazole, posaconazole, voriconazole and amphotericin B. Treatment with sequential administration of intravenous amphotericin B with voriconazole followed by itraconazole led to the resolution of the lesion.


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