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Combination of Six Individual Derivatives of the Pom-1 Antibiofilm Peptide Doubles Their Efficacy against Invasive and Multi-Resistant Clinical Isolates of the Pathogenic Yeast Candida albicans
Pharmaceutics. 2022 Jun 24; 14(7)P

Abstract

In previous studies, derivatives of the peptide Pom-1, which was originally extracted from the freshwater mollusk Pomacea poeyana, showed an exceptional ability to specifically inhibit biofilm formation of the laboratory strain ATCC 90028 as a model strain of the pathogenic yeast Candida albicans. In follow-up, here, we demonstrate that the derivatives Pom-1A to Pom-1F are also active against biofilms of invasive clinical C. albicans isolates, including strains resistant against fluconazole and/or amphotericin B. However, efficacy varied strongly between the isolates, as indicated by large deviations in the experiments. This lack of robustness could be efficiently bypassed by using mixtures of all peptides. These mixed peptide preparations were active against biofilm formation of all the isolates with uniform efficacies, and the total peptide concentration could be halved compared to the original MIC of the individual peptides (2.5 µg/mL). Moreover, mixing the individual peptides restored the antifungal effect of fluconazole against fluconazole-resistant isolates even at 50% of the standard therapeutic concentration. Without having elucidated the reason for these synergistic effects of the peptides yet, both the gain of efficacy and the considerable increase in efficiency by combining the peptides indicate that Pom-1 and its derivatives in suitable formulations may play an important role as new antibiofilm antimycotics in the fight against invasive clinical infections with (multi-) resistant C. albicans.

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Authors+Show Affiliations

Häring M
Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Amann V
Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Kissmann AK
Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Max Planck Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany.
Herberger T
Max Planck Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany.
Synatschke C
Max Planck Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany.
Kirsch-Pietz N
Max Planck Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany.
Perez-Erviti JA
Center for Protein Studies, Faculty of Biology, University of Havana, 25 Street, Havana 10400, Cuba.
Otero-Gonzalez AJ
Center for Protein Studies, Faculty of Biology, University of Havana, 25 Street, Havana 10400, Cuba.
Morales-Vicente F
Synthetic Peptides Group, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba.
Andersson J
AIT Austrian Institute of Technology GmbH, Giefinggasse 4, 1210 Vienna, Austria.
Weil T
Max Planck Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany.
Stenger S
Institute for Medical Microbiology and Hygiene, University Hospital Ulm, 89081 Ulm, Germany.
Rodríguez A
Core Facility for Functional Peptidomics, Ulm Peptide Pharmaceuticals (U-PEP), Faculty of Medicine, Ulm University, 89081 Ulm, Germany. Core Unit of Mass Spectrometry and Proteomics, Faculty of Medicine, Ulm University, 89081 Ulm, Germany.
Ständker L
Core Facility for Functional Peptidomics, Ulm Peptide Pharmaceuticals (U-PEP), Faculty of Medicine, Ulm University, 89081 Ulm, Germany.
Rosenau F
Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Max Planck Institute for Polymer Research Mainz, Ackermannweg 10, 55128 Mainz, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35890228

Citation

Häring, Michelle, et al. "Combination of Six Individual Derivatives of the Pom-1 Antibiofilm Peptide Doubles Their Efficacy Against Invasive and Multi-Resistant Clinical Isolates of the Pathogenic Yeast Candida Albicans." Pharmaceutics, vol. 14, no. 7, 2022.
Häring M, Amann V, Kissmann AK, et al. Combination of Six Individual Derivatives of the Pom-1 Antibiofilm Peptide Doubles Their Efficacy against Invasive and Multi-Resistant Clinical Isolates of the Pathogenic Yeast Candida albicans. Pharmaceutics. 2022;14(7).
Häring, M., Amann, V., Kissmann, A. K., Herberger, T., Synatschke, C., Kirsch-Pietz, N., Perez-Erviti, J. A., Otero-Gonzalez, A. J., Morales-Vicente, F., Andersson, J., Weil, T., Stenger, S., Rodríguez, A., Ständker, L., & Rosenau, F. (2022). Combination of Six Individual Derivatives of the Pom-1 Antibiofilm Peptide Doubles Their Efficacy against Invasive and Multi-Resistant Clinical Isolates of the Pathogenic Yeast Candida albicans. Pharmaceutics, 14(7). https://doi.org/10.3390/pharmaceutics14071332
Häring M, et al. Combination of Six Individual Derivatives of the Pom-1 Antibiofilm Peptide Doubles Their Efficacy Against Invasive and Multi-Resistant Clinical Isolates of the Pathogenic Yeast Candida Albicans. Pharmaceutics. 2022 Jun 24;14(7) PubMed PMID: 35890228.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination of Six Individual Derivatives of the Pom-1 Antibiofilm Peptide Doubles Their Efficacy against Invasive and Multi-Resistant Clinical Isolates of the Pathogenic Yeast Candida albicans AU - Häring,Michelle, AU - Amann,Valerie, AU - Kissmann,Ann-Kathrin, AU - Herberger,Tilmann, AU - Synatschke,Christopher, AU - Kirsch-Pietz,Nicole, AU - Perez-Erviti,Julio A, AU - Otero-Gonzalez,Anselmo J, AU - Morales-Vicente,Fidel, AU - Andersson,Jakob, AU - Weil,Tanja, AU - Stenger,Steffen, AU - Rodríguez,Armando, AU - Ständker,Ludger, AU - Rosenau,Frank, Y1 - 2022/06/24/ PY - 2022/05/17/received PY - 2022/06/14/revised PY - 2022/06/21/accepted PY - 2022/7/27/entrez PY - 2022/7/28/pubmed PY - 2022/7/28/medline KW - antimicrobial peptides KW - combination therapy KW - invasive clinical isolates JF - Pharmaceutics JO - Pharmaceutics VL - 14 IS - 7 N2 - In previous studies, derivatives of the peptide Pom-1, which was originally extracted from the freshwater mollusk Pomacea poeyana, showed an exceptional ability to specifically inhibit biofilm formation of the laboratory strain ATCC 90028 as a model strain of the pathogenic yeast Candida albicans. In follow-up, here, we demonstrate that the derivatives Pom-1A to Pom-1F are also active against biofilms of invasive clinical C. albicans isolates, including strains resistant against fluconazole and/or amphotericin B. However, efficacy varied strongly between the isolates, as indicated by large deviations in the experiments. This lack of robustness could be efficiently bypassed by using mixtures of all peptides. These mixed peptide preparations were active against biofilm formation of all the isolates with uniform efficacies, and the total peptide concentration could be halved compared to the original MIC of the individual peptides (2.5 µg/mL). Moreover, mixing the individual peptides restored the antifungal effect of fluconazole against fluconazole-resistant isolates even at 50% of the standard therapeutic concentration. Without having elucidated the reason for these synergistic effects of the peptides yet, both the gain of efficacy and the considerable increase in efficiency by combining the peptides indicate that Pom-1 and its derivatives in suitable formulations may play an important role as new antibiofilm antimycotics in the fight against invasive clinical infections with (multi-) resistant C. albicans. SN - 1999-4923 UR - https://www.unboundmedicine.com/medline/citation/35890228/Combination_of_Six_Individual_Derivatives_of_the_Pom_1_Antibiofilm_Peptide_Doubles_Their_Efficacy_against_Invasive_and_Multi_Resistant_Clinical_Isolates_of_the_Pathogenic_Yeast_Candida_albicans DB - PRIME DP - Unbound Medicine ER -