The relative lower anti-Candida activity of the shorter lipopeptides could be related to their reduced ability to permeate fungal membranes, because of their low hydrophobic character to drive oligomerization (Malina
& Shai, 2005). The effect of various concentrations of the purified anti-Candida compounds on human erythrocytes is reported in Table 4. The compound a1 showed a weak hemolytic activity (50% hemolysis at 68.26 μM) compared with a2 and a3 (50% hemolysis at 37.41 and 22.14 μM, respectively). This could be due to their low hydrophobicity, and therefore, limited ability to oligomerize, which is an important requirement for both the hemolytic and antifungal activity of an antimicrobial peptide. Prior studies showed Bioactive Compound Library order a direct correlation between the fatty acid chain length of surfactin lipopeptides and hemolytic activity (Kracht et al., 1999). It is noticeable that the hemolytic activity of the lipopeptide bacircines is also dependent on the length of the aliphatic side chain and that hemolysis is provoked by the insertion of the fatty acid chain into the phospholipid bilayer (Prokof’eva et al., 1999). Similarly, iturins A are able to lyse human erythrocytes in a dose-dependent manner (100% Cilomilast solubility dmso hemolysis at 25 μM) (Quentin et al., 1982; Aranda et al., 2005). This
limits their potential usage in clinical therapy (Besson & Michel, 1984; Aranda et al., 2005; Oleinikova et al., 2005; Ramarathnam et al., 2007; Chen et al., 2009). Nevertheless, we found that compound a3 with a long fatty acid chain exhibited a strong inhibitory effect (MFC value between 7.38 and 14.76 μM) against PIK3C2G most tested strains
of C. albicans causing mucous and cutaneous infections. Note that at these concentrations a3 compound showed a reduced hemolytic activity (17% and 35%). However, when tested against some pathogenic C. albicans strains causing finger nail candidiasis (C. albicans sp. 265 FN and C. albicans sp. 311 FN), compound a3 exhibited both higher MFC values (between 29.53 and 59.07 μM) and hemolytic activity (between 65.91% and 99.64%). Overall, for the treatment of such pathogenic strains causing cutaneous candidiasis, a local application of the a3 compound rather than a systemic or an oral administration is possible. In conclusion, our data have indicated that B. subtilis produce anti-Candida lipopeptides that might be used to treat cutaneous infections. This work was supported by grants from the ‘Ministère de l’Enseignement Supérieur et de la Recherche Scientifique’ of Tunisia. We thank Prof. E. Aouani for valuable discussion and critical reading of the manuscript. “
“The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK.