HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients.

The objective of this study was to elucidate the proteomic mechanisms of drug resistance in HIV-infected African patients. Cell membrane fractions from forty oral Candida isolates isolated from African HIV-positive patients were analysed using HPLC-MS with the aim of identifying proteins associated with their pathogenicity and drug resistance. Heat shock proteins that mediate the fungicidal activity of salivary peptides were found in all tested Candida fractions, with pH-responsive proteins associated with increased pathogenicity only being present in the three most commonly isolated species. ABC multidrug transporter efflux pumps and estrogen binding proteins were only found in C. albicans fractions, while ergosterol biosynthesis proteins were identified in four species. The combination of various adherence, invasion, upregulation and efflux pump mechanisms appear to be instrumental for the Candida host colonization and drug resistance emergence in HIV-infected individuals.

Measuring Streptococcus mutans, Streptococcus sanguinis and Candida albicans biofilm formation using a real-time impedance-based system.

Candida albicans and streptococci are amongst the most common fungal and bacterial organisms present in the oral cavity, with a growing body of evidence implicating C. albicans in increased caries severity and in the formation of the cariogenic biofilm. However, the interactive mechanisms between cariogenic streptococci and Candida are yet to be elucidated. In this study, the real-time biofilm formation of C. albicans, S. mutans and S. sanguinis was assessed individually and in combination using the xCELLigence system, an impedance-based microbial biofilm monitoring system. The impedance signal was the highest for C. albicans, followed by S. mutans and S. sanguinis. Although the streptococcal mixed adhesion was found to follow a similar trend to that of S. sanguinis, the introduction of C. albicans resulted in higher adhesion patterns, with the combined growth of S. sanguinis and C. albicans and the combination of all three species resulting in higher biofilm formation than any of the individual organisms over time. This study, the first to use impedance for real-time monitoring of interkingdom biofilms, adds to the body of evidence that C. albicans and oral streptococcal adhesion are interlinked and suggests that interkingdom interactions induce changes in the oral biofilm dynamics over time.

K21 Compound, a Potent Antifungal Agent: Implications for the Treatment of Fluconazole-Resistant HIV-Associated Candida Species.

Background/Objectives: With mucocutaneous candidiasis being highly prevalent in HIV patients, the emergence of fluconazole-resistant Candida species forms a major challenge in treating and eradicating these infections. The objective of this study was to establish the antifungal activity of K21, a membrane-rupturing antimicrobial compound derived from a silica quaternary ammonium compound (SiQAC) with tetraethoxysilane (TEOS). Methods: The study sample included 81 Candida species of which 9 were type strains and 72 were clinical isolates. Minimum inhibitory concentrations, synergy, fractional inhibitory concentration index (FICI), and time kill assays were determined by broth microdilution. Electron microscopy (EM) was used to determine the qualitative changes brought about after treatment with K21. Results: K21 inhibited the growth of all fluconazole-resistant and susceptible Candida strains with only 2 h of exposure required to effectively kill 99.9% of the inoculum, and a definite synergistic effect was observed with a combination of K21 and fluconazole. EM demonstrated the presence of two forms of extracellular vesicles indicative of biofilm formation and cell lysis. Conclusion: The study established the efficacy of K21 as an antifungal agent and with fluconazole-resistant candidiasis on the increase, the development of K21 can provide a promising alternative to combat acquired drug resistance.