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Antimicrobial Agents and Chemotherapy, May 2001, p. 1367-1373, Vol. 45, No. 5
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.5.1367-1373.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Anticandida Activity Is Retained in P-113, a 12-Amino-Acid Fragment of Histatin 5

David M. Rothstein,1,* Peter Spacciapoli,1 Linh T. Tran,1 Tao Xu,2,dagger F. Donald Roberts,1 Mauro Dalla Serra,3 Deborah K. Buxton,1 Frank G. Oppenheim,2 and Phillip Friden1

Periodontix, Inc., Watertown, Massachusetts1; Department of Periodontology and Oral Biology, Boston University, Boston, Massachusetts2; and Centro di Fisica Stati Aggregati, Trento, Italy3

Received 13 September 2000/Returned for modification 25 October 2000/Accepted 6 February 2001

Through the analysis of a series of 25 peptides composed of various portions of the histatin 5 sequence, we have identified P-113, a 12-amino-acid fragment of histatin 5, as the smallest fragment that retains anticandidal activity comparable to that of the parent compound. Amidation of the P-113 C terminus increased the anticandidal activity of P-113 approximately twofold. The three histidine residues could be exchanged for three hydrophobic residues, with the fragment retaining anticandidal activity. However, the change of two or more of the five basic (lysine and arginine) residues to uncharged residues resulted in a substantial loss of anticandidal activity. A synthetic D-amino-acid analogue, P-113D, was as active against Candida albicans as the L-amino-acid form. In vitro MIC tests in low-ionic-strength medium showed that P-113 has potent activity against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. These results identify P-113 as a potential antimicrobial agent in the treatment of oral candidiasis.

* Corresponding author. Mailing address: 107 Cedar St., Lexington, MA 02472. Phone: (781) 862-3801. Fax: (617) 926-4776. E-mail: drothstein{at}rcn.com.

dagger Present address: Colgate-Palmolive Technical Center, Piscataway, NJ 08855.

Antimicrobial Agents and Chemotherapy, May 2001, p. 1367-1373, Vol. 45, No. 5
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.5.1367-1373.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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