Downloaded from www.microbiologyresearch.org by IP: 54.167.185.24 On: Fri, 28 Oct 2016 08:33:58 Journal of Medical Microbiology (2005), 54, 647–653 DOI 10.1099/jmm.0.45919-0 45919 & 2005 SGM Printed in Great Britain 647 Correspondence N. Ivanovska nina@microbio.bas.bg Received 7 October 2004 Accepted 1 March 2005 Ibogaine reduces organ colonization in murine systemic and gastrointestinal Candida albicans infections M. Yordanov, 1 P. Dimitrova, 1 S. Patkar, 2 S. Falcocchio, 3 E. Xoxi, 3 L. Saso 3 and N. Ivanovska 1 1 Department of Immunology, Institute of Microbiology, 26 G. Bonchev Str., 1113 Sofia, Bulgaria 2 Novozymes A/S, Novo Alle ´ , DK-2880, Bagsvaerd, Denmark 3 Department of Human Physiology and Pharmacology ‘Vittorio Erspame’, University of Rome ‘La Sapienza’, P. le Aldo Moro 5, 00185 Rome, Italy In the present study the effect of the indole alkaloid ibogaine on the in vitro lipolytic activity and adherence to epithelial cells of Candida albicans was investigated. The substance was administered intraperitoneally at a dose of 5 mg kg À1 day À1 in mice with disseminated and gastrointestinal C. albicans infections. Ibogaine significantly decreased the rate of mortality and the number of C. albicans c.f.u. recovered from the kidney, liver and spleen. Ibogaine interfered with the early stages of both disseminated and gastrointestinal C. albicans infections but did not reduce the number of C. albicans c.f.u. in the organs at the late phase of infections. The development of a specific immune response was not influenced by ibogaine, since the delayed-type hypersensitivity reaction to C. albicans and the production of interferon (IFN)-ª were similar in control and ibogaine- treated mice. The combined use of amphotericin B plus ibogaine in the treatment of mice with gastrointestinal infection reduced organ colonization more strongly than each substance alone. INTRODUCTION Candida albicans is an opportunistic fungal pathogen with a rising incidence of severe disseminated infections leading to fatal outcomes in humans (Fidel et al., 1999; Komshian et al., 1989; Pfaller, 1996). A number of factors have contributed to this, for example the wide use of immunosuppressive therapies and the increased cases of immune-deficiency diseases, such as AIDS (Shearer, 1998). The limited number of effective antifungals against C. albicans is further reduced by the appearance of drug-resistant species. The discovery of new compounds with different mechanisms of action is a challenge in antifungal drug research. While immunity to Candida has been thoroughly investi- gated, the factors connected with the early penetration of the yeast into the host cells are less defined and exploited. Micro- organisms can damage host cell membranes through secre- tion of different proteolytic and lipolytic enzymes. It has been proven that C. albicans produces extracellular lipases, and since the characterization of the gene LIP1 (Fu et al., 1997) nine new members of a family encoding lipases have been identified (Hube et al., 2000). An important observation is that some of these LIP genes are expressed in infected organs during systemic C. albicans infection. These data suggest that lipases might be involved in the pathogenesis of the yeast. Phospholipases belong to a heterogeneous group of enzymes capable of destroying cell membranes. Many investigations support the view that they act as pathogenic factors in protozoan (Saffer & Schwartzman, 1991), bacterial (Portnoy et al., 1994; Songer, 1997; Titball, 1993) and fungal (Cox et al., 2001; Leidich et al., 1998) infections. Genes encoding phospholipase B and C have recently been cloned (Bennett et al., 1998; Sugiyama et al., 1999). According to a classifica- tion of phospholipases, based on the type of ester link that is cleaved, a single enzyme can express phospholipase B activity and also lysophospholipase and transacyclase activity. If it is the case that all these activities are controlled by one gene product, it is difficult to correlate a certain biological effect with a single enzyme. In vivo data demonstrate that phos- pholipase-deficient C. albicans mutants are less invasive (Ghannoum, 2000; Mukherjee et al., 2001). Targeted gene disruption is one of the most promising approaches to evaluate the contribution of different extracellular products to the virulence of C. albicans. Using this method, Leidich et al. (1998) showed that the disruption of a gene encoding a phospholipase B had no effect on yeast growth but signifi- cantly reduced its penetration into host cells and its virulence Abbreviations: AmB, amphotericin B; DTH, delayed-type hypersensitivity reaction; IFN, interferon; i.v., intravenously.