Successful colonization of the acidic vaginal niche by C. glabrata and C. albicans depends on their ability to cope with the presence of lactic and acetic acids produced by commensal microbiota. As such, the inhibitory effect of these acids at a low pH in growth of C. glabrata and C. albicans was investigated. The effect of the presence of these organic acids in tolerance of the two Candida species to azoles used in treatment of vaginal infections was also investigated including eventual synergistic effects. Under the different experimental conditions tested lactic acid exerted no significant inhibitory effect against C. albicans or C. glabrata, contrasting with the generalized impression that the production of this acid is on the basis of the protective effect exerted by vaginal lactobacilii. Differently, C. glabrata and C. albicans exhibited susceptibility to acetic acid, more prominent at lower pHs and stronger for the latter species. Synergism between acetic acid and azoles was observed both for C. albicans and C. glabrata, while lactic acid-azole synergism was only efficient against C. albicans. Altogether our in vitro results indicate that tolerance to acetic acid at a low pH may play a more relevant role than tolerance to lactic acid in determining competitiveness in the vaginal tract of C. albicans and C. glabrata including under azole stress. Treatment of vaginal candidiasis with azoles may depend on the level of acetic and lactic acids present and improvements could be achieved synergizing the azole with these acids.

The present work follows a previous report describing the antibacterial activity of silver camphorimine complexes of general formula [Ag(NO3)L]. The synthesis and demonstration of the antifungal and antibacterial activity of three novel [Ag(NO3)L] complexes (named 1, 2 and 3) is herein demonstrated. This work also shows for the first time that the previously studied complexes (named 4 to 8) also exert antifungal activity. The antibacterial activity of complexes was evaluated against Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia contaminans and Escherichia coli strains, while antifungal activity was tested against the Candida species C. albicans, C. glabrata, C. parapsilosis and C. tropicalis. The antimicrobial activity of the complexes ranged from very high (complex 4) to moderate (complex 6) or low (complex 8), depending on the structural and electronic characteristics of the camphorimine ligands. Notably, the highest antibacterial and anti-Candida activities do not coincide in the same complex and in some cases they were even opposite, as is the case of complex 4 which exhibits a high anti-bacterial and low antifungal activity. These distinct results suggest that the complexes may have different mechanisms against prokaryotic and eukaryotic cells. The antifungal activity of the Ag(I) camphorimine complexes (in particular of complex 1) was found to be very high (MIC = 2 μg/mL) against C. parapsilosis, being also registered a prominent activity against C. tropicalis and C. glabrata. None of the tested compounds inhibited C. albicans growth, being this attributed to the ability of these yeast cells to mediate the formation of less toxic Ag nanoparticles, as confirmed by Scanning Electron Microscopy images. The high antibacterial and anti-Candida activities of the here studied camphorimine complexes, especially of complexes 1 and 7, suggests a potential therapeutic application for these compounds.