TY  - JOUR
A1  - John, Cathy N.
A1  - Abrantes, Pedro M. D. S.
A1  - Prusty, Bhupesh K.
A1  - Ablashi, Dharam V.
A1  - Africa, Charlene W. J.
T1  - K21 Compound, a Potent Antifungal Agent: Implications for the Treatment of Fluconazole-Resistant HIV-Associated Candida Species
JF  - Frontiers in Microbiology
N2  - 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.
KW  - HIV-associated candidiasis
KW  - antimicrobial compounds
KW  - Candida
KW  - fluconazole
KW  - antifungal susceptibility
KW  - broth microdilution
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323505
VL  - 10
ER  - 
TY  - JOUR
A1  - Halder, Luke D.
A1  - Abdelfatah, Mahmoud A.
A1  - Jo, Emeraldo A. H.
A1  - Jacobsen, Ilse D.
A1  - Westermann, Martin
A1  - Beyersdorf, Niklas
A1  - Lorkowski, Stefan
A1  - Zipfel, Peter F.
A1  - Skerka, Christine
T1  - Factor H binds to extracellular DNA traps released from human blood monocytes in response to Candida albicans
JF  - Frontiers in Immunology
N2  - Upon systemic infection with human pathogenic yeast Candida albicans (C. albicans), human monocytes and polymorph nuclear neutrophilic granulocytes are the first immune cells to respond and come into contact with C. albicans. Monocytes exert immediate candidacidal activity and inhibit germination, mediate phagocytosis, and kill fungal cells. Here, we show that human monocytes spontaneously respond to C. albicans cells via phagocytosis, decondensation of nuclear DNA, and release of this decondensed DNA in the form of extracellular traps (called monocytic extracellular traps: MoETs). Both subtypes of monocytes (CD14\(^{++}\)CD16\(^−\)/CD14\(^+\)CD16\(^+\)) formed MoETs within the first hours upon contact with C. albicans. MoETs were characterized by the presence of citrullinated histone, myeloperoxidase, lactoferrin, and elastase. MoETs were also formed in response to Staphylococcus aureus and Escherichia coli, indicating a general reaction of monocytes to infectious microbes. MoET induction differs from extracellular trap formation in macrophages as MoETs are not triggered by simvastatin, an inhibitor of cholesterol synthesis and inducer of extracellular traps in macrophages. Extracellular traps from both monocytes and neutrophils activate complement and C3b is deposited. However, factor H (FH) binds via C3b to the extracellular DNA, mediates cofactor activity, and inhibits the induction of the inflammatory cytokine interleukin-1 beta in monocytes. Altogether, the results show that human monocytes release extracellular DNA traps in response to C. albicans and that these traps finally bind FH via C3b to presumably support clearance without further inflammation.
KW  - Candida
KW  - monocytes
KW  - DNA traps
KW  - MPO
KW  - factor H
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181127
VL  - 7
ER  -