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2-hydroxyisocaproic acid is fungicidal for Candida and Aspergillus species

Authors

  • M. Sakko,

    1. Finnish Doctoral Program of Oral Sciences, Turku, Finland
    2. Institute of Dentistry, University of Oulu, Oulu, Finland
    3. Institute of Dentistry, University of Helsinki, Helsinki, Finland
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  • C. Moore,

    1. Manchester Academic Health Science Centre, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, The University of Manchester, Manchester, UK
    2. University Hospital South Manchester and Mycology Reference Centre Manchester, NHS Foundation Trust, Manchester, UK
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  • L. Novak-Frazer,

    1. Manchester Academic Health Science Centre, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, The University of Manchester, Manchester, UK
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  • V. Rautemaa,

    1. Manchester Academic Health Science Centre, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, The University of Manchester, Manchester, UK
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  • T. Sorsa,

    1. Institute of Dentistry, University of Helsinki, Helsinki, Finland
    2. Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland
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  • P. Hietala,

    1. Extracta Ltd, Vantaa, Finland
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  • A. Järvinen,

    1. Division of Infectious Diseases, Department of Medicine, Helsinki University Hospital, Helsinki, Finland
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  • P. Bowyer,

    1. Manchester Academic Health Science Centre, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, The University of Manchester, Manchester, UK
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  • L. Tjäderhane,

    1. Institute of Dentistry, University of Oulu, Oulu, Finland
    2. Institute of Dentistry, University of Turku, Turku, Finland
    3. Oulu University Hospital, Oulu, Finland
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  • R. Rautemaa

    Corresponding author
    1. Institute of Dentistry, University of Helsinki, Helsinki, Finland
    2. Manchester Academic Health Science Centre, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, The University of Manchester, Manchester, UK
    3. University Hospital South Manchester and Mycology Reference Centre Manchester, NHS Foundation Trust, Manchester, UK
    4. Department of Oral and Maxillofacial Diseases, Helsinki University Hospital, Helsinki, Finland
    • Correspondence: R. Rautemaa-Richardson, Education & Research Centre, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK.

      Tel.: +44 161 291 5914. Fax: +44 161 291 5806.

      E-mail: riina.richardson@manchester.ac.uk

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Summary

The amino acid derivative 2-hydroxyisocaproic acid (HICA) is a nutritional additive used to increase muscle mass. Low levels can be detected in human plasma as a result of leucine metabolism. It has broad antibacterial activity but its efficacy against pathogenic fungi is not known. The aim was to test the efficacy of HICA against Candida and Aspergillus species. Efficacy of HICA against 19 clinical and reference isolates representing five Candida and three Aspergillus species with variable azole antifungal sensitivity profiles was tested using a microdilution method. The concentrations were 18, 36 and 72 mg ml−1. Growth was determined spectrophotometrically for Candida isolates and by visual inspection for Aspergillus isolates, viability was tested by culture and impact on morphology by microscopy. HICA of 72 mg ml−1 was fungicidal against all Candida and Aspergillus fumigatus and Aspergillus terreus isolates. Lower concentrations were fungistatic. Aspergillus flavus was not inhibited by HICA. HICA inhibited hyphal formation in susceptible Candida albicans and A. fumigatus isolates and affected cell wall integrity. In conclusion, HICA has broad antifungal activity against Candida and Aspergillus at concentrations relevant for topical therapy. As a fungicidal agent with broad-spectrum bactericidal activity, it may be useful in the topical treatment of multispecies superficial infections.

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