Efficacy of human salivary mucin MUC7-derived peptide and histatin 5 in a murine model of candidiasis Giuseppe Intini, Alfredo Aguirre, Libuse Anna Bobek * Departments of Oral Biology and Oral Diagnostic Sciences, School of Dental Medicine, University at Buffalo, The State University of New York, 109 Foster Hall, 3435 Main Street, Buffalo, NY 14214-3092, USA Received 7 January 2003; accepted 15 April 2003 Abstract MUC7 16-mer (residues 36 /51 of human salivary mucin, MUC7) and histatin 5 possess potent in vitro antifungal activity. In the present study, we haveevaluated the efficacy of these peptides in vivo using the experimental model of murine vulvo-vaginal candidiasis. The treatment groups included MUC7 16-mer, histatin 5, clotrimazole (all in pluronic F127 gel), and placebo (gel alone). Mice were treated intravaginally for 7 consecutive days. At the end of the treatment, anticandidal activities were assessed by colony counts and by histological examination. All groups except clotrimazole presented positive cultures; no statistically significant differences were found in fungal burden amongst placebo and any treatment group except clotrimazole. Histopathological findings confirmed the microbiological results; all groups with the exception of clotrimazole showed variable signs of infection. # 2003 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Candida albicans ; Anticandidal agents; Clotrimazole; Pluronic F127; In vivo 1. Introduction Fungal pathogens are responsible for many infections that afflict people with weakened immune systems, such as organ transplant and chemotherapy patients, as well as persons with AIDS [1,2]. With the longer life expectancy of immunocompromised patients, fungal infections have recently become of great medical rele- vance and treatments for these infections assume an important role in terms of patient quality of life. However, the combination of prolonged treatment regimes with the restricted number of available effective antifungal agents can induce the emergence of resistant pathogenic fungal strains, constituting a serious threat to public health [3]. In this respect the search for new antifungal therapeutic agents assumes a relevant role. Naturally occurring antimicrobial peptides [4] are an attractive treatment option for fungal infections. Among these peptides, human salivary histatin(s) and salivary mucin MUC7-derived peptide(s) are known to possess potent antifungal activity in vitro [5  /9]. They have been shown to be effective against a broad spectrum of fungi. More importantly, they exhibit excellent in vitro activity against fungi such as Candida albicans and Cryptococcus neoformans , which are associated with infections in immunocompromised or diabetics patients [9,10]. They were also found to be effective against azole-resistant C. albicans and amphotericin-B-resistant C. neoformans [10]. However, no in vivo studies have been performed to validate these in vitro data. Histatin 5 [11  /13] and MUC7-derived peptides [14] were also found to possess in vitro antibacterial activity, and histatin derivatives to have some efficacy as therapeutic agents against experi- mental gingivitis in beagle dogs and in human clinical trials [15  /17]. The low-molecular weight human salivary mucin, MUC7, is a 357aa protein which in its entire length has no appreciable in vitro anticandidal activity [18]. On the other hand, peptides derived from the N-terminus of MUC7 such as MUC7 51-mer (also known as MUC7 D1) and shorter peptides [9,18], including MUC7 16- mer (residues 36  /51 from the N-terminus of MUC7), showed potent in vitro anticandidal activity. Therefore, * Corresponding author. Tel.:  /1-716-829-2465; fax:  /1-716-829- 3942. E-mail address: lbobek@buffalo.edu (L.A. Bobek). International Journal of Antimicrobial Agents 22 (2003) 594  /600 www.ischemo.org 0924-8579/03/$30 # 2003 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/S0924-8579(03)00243-7