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Microbiology Society logo Microbiology

Volume 172, Issue 3

Antifungal activity of the antimicrobial peptide RP557 against priority fungal pathogens Open Access

Abstract

Natural host defence molecules, part of innate immunity and the first line of defence, are evolutionarily conserved. Some pharmaceutical properties undesirable for clinical use led to the rational design of synthetic molecules with constructed peptide arrangements, giving a novel therapeutic avenue. A prior publication showed synthetic peptide RP557 inhibition and killing of fluconazole-sensitive and resistant species isolates, biofilm inhibition, no resistance induction, direct membrane action, negligible mammalian cell toxicity and topical efficacy in a rodent vaginal candidiasis model. These findings highlight the relevance of investigating RP557 activity against other fungal pathogens.

We evaluated the antifungal spectrum of the RP557 against World Health Organization-listed priority fungal pathogens, including endemic and skin fungal pathogens, both alone and in combination with commercial antifungal drugs.

The antifungal spectrum was evaluated by broth dilution vs. clinical isolates, and we present 76 MICs (mcg ml) performed according to M27 or M38 CLSI documents, 35 checkerboard interactions with antifungals and 10 minimum fungicidal determinations.

Overall impression is robust activity vs. chromoblastomycosis and mycetoma species, and spp.; broad MIC ranges within most species, least activity vs. and spp.; and some promising drug interactions vs. spp. and .

Additional efficacy data is needed. Topical therapy could give local concentrations exceeding MICs, and burn or trauma prophylaxis or treatments are attractive potential targets owing to RP557 panmicrobial properties.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Aspergillus spp. , Candida auris , chromoblastomycosis and mycetoma species , Cryptococcus neoformans , dermatophytes and Sporothrix spp.
Funding
This study was supported by the:
  • Riptide Bioscience, Vallejo, CA (Award Riptide Bioscience, Vallejo, CA)
    • Principal Award Recipient: DavidA. Stevens
© 2026 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2026-03-02
2026-03-16

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References

  1. Lockhart SR, Chowdhary A, Gold JAW. The rapid emergence of antifungal-resistant human-pathogenic fungi. Nat Rev Microbiol 2023; 21:818–832 [View Article] [PubMed]
     [Google Scholar]
  2. Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM et al. Tackling the emerging threat of antifungal resistance to human health. Nat Rev Microbiol 2022; 20:557–571 [View Article] [PubMed]
     [Google Scholar]
  3. World Health Organization, WHO Fungal Priority Pathogens List to Guide Research, Development and Public Health Action Geneva: World Health Organization; 2022
     [Google Scholar]
  4. Liu F, Hu Z-D, Zhao X-M, Zhao W-N, Feng Z-X et al. Phylogenomic analysis of the Candida auris-Candida haemuli clade and related taxa in the Metschnikowiaceae, and proposal of thirteen new genera, fifty-five new combinations and nine new species. Persoonia 2024; 52:22–43 [View Article] [PubMed]
     [Google Scholar]
  5. Global Action Fund for Fungal Infections (GAFFI) 2023 https://gaffi.org/why/fungi-fungal-infections accessed 24 February 2025
  6. Queiroz-Telles F, Fahal AH, Falci DR, Caceres DH, Chiller T et al. Neglected endemic mycoses. Lancet Infect Dis 2017; 17:e367–e377 [View Article] [PubMed]
     [Google Scholar]
  7. World Health Organization, WHO Neglected tropical diseases; 2023 https://www.who.int/health-topics/neglected-tropical-diseases
  8. Rabello VBS, Almeida MA, Bernardes-Engemann AR, Almeida-Paes R, de Macedo PM et al. The historical burden of sporotrichosis in Brazil: a systematic review of cases reported from 1907 to 2020. Braz J Microbiol 2022; 53:231–244 [View Article] [PubMed]
     [Google Scholar]
  9. Xavier MO, Poester VR, Trápaga MR, Stevens DA. Sporothrix brasiliensis: epidemiology, therapy, and recent developments. J Fungi 2023; 9:921 [View Article] [PubMed]
     [Google Scholar]
  10. Ciociola T, Giovati L, Conti S, Magliani W, Santinoli C et al. Natural and synthetic peptides with antifungal activity. Future Med Chem 2016; 8:1413–1433 [View Article]
     [Google Scholar]
  11. Lewies A, Wentzel JF, Jacobs G, Du Plessis LH. The potential use of natural and structural analogues of antimicrobial peptides in the fight against neglected tropical diseases. Molecules 2015; 20:15392–15433 [View Article]
     [Google Scholar]
  12. Lima PG, Oliveira JTA, Amaral JL, Freitas CDT, Souza PFN. Synthetic antimicrobial peptides: characteristics, design, and potential as alternative molecules to overcome microbial resistance. Life Sci 2021; 278:119647 [View Article] [PubMed]
     [Google Scholar]
  13. Sheehan G, Bergsson G, McElvaney NG, Reeves EP, Kavanagh K. The human cathelicidin antimicrobial peptide LL-37 promotes the growth of the pulmonary pathogen Aspergillus fumigatus. Infect Immun 2018; 86:e00097-18 [View Article] [PubMed]
     [Google Scholar]
  14. Song J, Zhang S, Xing J, Zhang L, Wang J et al. Optimizing therapeutic efficacy of antifungal peptides via strategic terminal amino acid modification. J Adv Res 2025; 74:555–570 [View Article] [PubMed]
     [Google Scholar]
  15. Li X, Zuo S, Wang B, Zhang K, Wang Y. Antimicrobial mechanisms and clinical application prospects of antimicrobial peptides. Molecules 2022; 27:2675 [View Article]
     [Google Scholar]
  16. Woodburn KW, Clemens LE, Jaynes J, Joubert L-M, Botha A et al. Designed antimicrobial peptides for recurrent vulvovaginal candidiasis treatment. Antimicrob Agents Chemother 2019; 63:e02690-18 [View Article]
     [Google Scholar]
  17. Mohsin J, Weerakoon S, Ahmed S, Puts Y, Al Balushi Z et al. A cluster of Candida auris blood stream infections in a tertiary care hospital in Oman from 2016 to 2019. Antibiotics 2020; 9:638 [View Article] [PubMed]
     [Google Scholar]
  18. CLSI Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard. CLSI Document M27-Ed4 2017
     [Google Scholar]
  19. CLSI Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard-Second Edition. CLSI Document M38-A2 2008
     [Google Scholar]
  20. Poester VR, Munhoz LS, Larwood D, Martinez M, Stevens DA et al. Potential use of Nikkomycin Z as an anti- Sporothrix spp. drug. Med Mycol 2021; 59:345–349 [View Article] [PubMed]
     [Google Scholar]
  21. Lim W, Verbon A, van de Sande W. Identifying novel drugs with new modes of action for neglected tropical fungal skin diseases (fungal skinNTDs) using an open source drug discovery approach. Expert Opin Drug Discov 2022; 17:641–659 [View Article] [PubMed]
     [Google Scholar]
  22. Santos DWCL, de Azevedo C de MPES, Vicente VA, Queiroz-Telles F, Rodrigues AM et al. The global burden of chromoblastomycosis. PLoS Negl Trop Dis 2021; 15:e0009611 [View Article] [PubMed]
     [Google Scholar]
  23. Elkheir LYM, Haroun R, Mohamed MA, Fahal AH. Madurella mycetomatis causing eumycetoma medical treatment: the challenges and prospects. PLoS Negl Trop Dis 2020; 14:e0008307 [View Article] [PubMed]
     [Google Scholar]
  24. Poester VR, Basso RP, Stevens DA, Munhoz LS, de Souza Rabello VB et al. Treatment of human sporotrichosis caused by Sporothrix brasiliensis. J Fungi 2022; 8:70 [View Article] [PubMed]
     [Google Scholar]
  25. Queiroz-Telles F, de Hoog S, Santos DWCL, Salgado CG, Vicente VA et al. Chromoblastomycosis. Clin Microbiol Rev 2017; 30:233–276 [View Article]
     [Google Scholar]
  26. Clemens LE, Jaynes J, Lim E, Kolar SS, Reins RY et al. Designed host defense peptides for the treatment of bacterial keratitis. Invest Ophthalmol Vis Sci 2017; 58:6273–6281 [View Article]
     [Google Scholar]
  27. Ramata-Stunda A, Boroduskis M, Kaktina E, Patetko L, Kalnenieks U et al. Comparative evaluation of existing and rationally designed novel antimicrobial peptides for treatment of skin and soft tissue infections. Antibiotics 2023; 12:551 [View Article] [PubMed]
     [Google Scholar]
  28. Vargas A, Garcia G, Rivara K, Woodburn K, Clemens LE et al. A designed host defense peptide for the topical treatment of MRSA-infected diabetic wounds. Int J Mol Sci 2023; 24:2143 [View Article] [PubMed]
     [Google Scholar]
  29. Woodburn KW, Jaynes J, Clemens LE. Designed antimicrobial peptides for topical treatment of antibiotic resistant acne vulgaris. Antibiotics 2020; 9:23 [View Article]
     [Google Scholar]
  30. Wu N, Fu S, Dai C, Hu L, Li J et al. DNA nanotube-carrying antimicrobial peptide confers improved anti-infective therapy. Nano Today 2024; 59:102508 [View Article] [PubMed]
     [Google Scholar]
  31. Li B, Zhang Y, Guo Q, He S, Fan J et al. Antibacterial peptide RP557 increases the antibiotic sensitivity of Mycobacterium abscessus by inhibiting biofilm formation. Sci Total Environ 2022; 807:151855 [View Article]
     [Google Scholar]
  32. Chakrabarti A, Bonifaz A, Gutierrez-Galhardo MC, Mochizuki T, Li S. Global epidemiology of sporotrichosis. Med Mycol 2015; 53:3–14 [View Article]
     [Google Scholar]
  33. Munhoz LS, Poester VR, Benelli JL, Melo AM, Trápaga MR et al. Effectiveness of diphenyl diselenide against experimental sporotrichosis caused by sporothrix brasiliensis. Med Mycol 2023; 61:myad035 [View Article]
     [Google Scholar]
  34. Sierra JM, Fusté E, Rabanal F, Vinuesa T, Viñas M. An overview of antimicrobial peptides and the latest advances in their development. Expert Opin Biol Ther 2017; 17:663–676 [View Article] [PubMed]
     [Google Scholar]
  35. Du H, Bing J, Hu T, Ennis CL, Nobile CJ et al. Candida auris: epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog 2020; 16:e1008921 [View Article] [PubMed]
     [Google Scholar]
  36. De Lucca AJ, Bland JM, Grimm C, Jacks TJ, Cary JW et al. Fungicidal properties, sterol binding, and proteolytic resistance of the synthetic peptide D4E1. Can J Microbiol 1998; 44:514–520 [View Article]
     [Google Scholar]
  37. Li T, Li L, Du F, Sun L, Shi J et al. Activity and mechanism of action of antifungal peptides from microorganisms: a review. Molecules 2021; 26:3438 [View Article] [PubMed]
     [Google Scholar]
  38. Ageitos JM, Sánchez-Pérez A, Calo-Mata P, Villa TG. Antimicrobial peptides (AMPs): ancient compounds that represent novel weapons in the fight against bacteria. Biochem Pharmacol 2017; 133:117–138 [View Article]
     [Google Scholar]
  39. Ballard E, Yucel R, Melchers WJG, Brown AJP, Verweij PE et al. Antifungal activity of antimicrobial peptides and proteins against Aspergillus fumigatus. J Fungi 2020; 6:65 [View Article] [PubMed]
     [Google Scholar]
  40. Baxter AA, Poon IK, Hulett MD. The lure of the lipids: how defensins exploit membrane phospholipids to induce cytolysis in target cells. Cell Death Dis 2017; 8:e2712 [View Article] [PubMed]
     [Google Scholar]
  41. Buda De Cesare G, Cristy SA, Garsin DA, Lorenz MC. Antimicrobial peptides: a new frontier in antifungal therapy. mBio 2020; 11:e02123-20 [View Article] [PubMed]
     [Google Scholar]
  42. Hacioglu M, Guzel CB, Savage PB, Tan ASB. Antifungal susceptibilities, in vitro production of virulence factors and activities of ceragenins against Candida spp. isolated from vulvovaginal candidiasis. Med Mycol 2019; 57:291–299 [View Article] [PubMed]
     [Google Scholar]
  43. Larwood DJ, Stevens DA. Antifungal activity of brilacidin, a nonpeptide host defense molecule. Antibiotics 2024; 13:405 [View Article]
     [Google Scholar]
  44. Li J, Fernández-Millán P, Boix E. Synergism between host defence peptides and antibiotics against bacterial infections. Curr Top Med Chem 2020; 20:1238–1263 [View Article]
     [Google Scholar]
  45. Lima PG, Souza PFN, Freitas CDT, Oliveira JTA, Dias LP et al. Anticandidal activity of synthetic peptides: mechanism of action revealed by scanning electron and fluorescence microscopies and synergism effect with nystatin. J Pept Sci 2020; 26:e3249 [View Article] [PubMed]
     [Google Scholar]
  46. Lyu Y, Yang Y, Lyu X, Dong N, Shan A. Antimicrobial activity, improved cell selectivity and mode of action of short PMAP-36-derived peptides against bacteria and Candida. Sci Rep 2016; 6:27258 [View Article] [PubMed]
     [Google Scholar]
  47. Mensa B, Howell GL, Scott R, DeGrado WF. Comparative mechanistic studies of brilacidin, daptomycin, and the antimicrobial peptide LL16. Antimicrob Agents Chemother 2014; 58:5136–5145 [View Article] [PubMed]
     [Google Scholar]
  48. Mookherjee N, Anderson MA, Haagsman HP, Davidson DJ. Antimicrobial host defence peptides: functions and clinical potential. Nat Rev Drug Discov 2020; 19:311–332 [View Article]
     [Google Scholar]
  49. Sahl H-G, Pag U, Bonness S, Wagner S, Antcheva N et al. Mammalian defensins: structures and mechanism of antibiotic activity. J Leukoc Biol 2005; 77:466–475 [View Article] [PubMed]
     [Google Scholar]
  50. Kurtz MB, Douglas CM. Lipopeptide inhibitors of fungal glucan synthase. J Med Vet Mycol 1997; 35:79–86 [View Article]
     [Google Scholar]
  51. Szymański M, Chmielewska S, Czyżewska U, Malinowska M, Tylicki A. Echinocandins - structure, mechanism of action and use in antifungal therapy. J Enzyme Inhib Med Chem 2022; 37:876–894 [View Article] [PubMed]
     [Google Scholar]
  52. Perlin DS. Mechanisms of echinocandin antifungal drug resistance. Ann N Y Acad Sci 2015; 1354:1–11 [View Article]
     [Google Scholar]
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Antifungal activity of the antimicrobial peptide RP557 against priority fungal pathogens
Microbiology 172, 001663 (2026); https://doi.org/10.1099/mic.0.001663
/content/journal/micro/10.1099/mic.0.001663
/content/journal/micro/10.1099/mic.0.001663
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