Oropharyngeal candidiasis is an opportunistic infection considered to be a harbinger of AIDS. The etiologic agent Candida albicans is a fungal species commonly colonizing human mucosal surfaces. However, under conditions of immune dysfunction, colonizing C. albicans can become an opportunistic pathogen causing superficial or even life-threatening infections. The reasons behind this transition, however, are not clear. In the oral cavity, salivary antimicrobial peptides are considered to be an important part of the host innate defense system in the prevention of microbial colonization. Histatin-5 specifically has exhibited potent activity against C. albicans. Our previous studies have shown histatin-5 levels to be significantly reduced in the saliva of HIV+ individuals, indicating an important role for histatin-5 in keeping C. albicans in its commensal stage. The versatility in the pathogenic potential of C. albicans is the result of its ability to adapt through the regulation of virulence determinants, most notably of which are proteolytic enzymes (Saps), involved in tissue degradation. In this study, we show that C. albicans cells efficiently and rapidly degrade histatin-5, resulting in loss of its anti-candidal potency. In addition, we demonstrate that this cellular activity is due to proteolysis by a member of the secreted aspartic proteases (Sap) family involved in C. albicans pathogenesis. Specifically, the proteolysis was attributed to Sap9, in turn identifying histatin-5 as the first host-specific substrate for that isoenzyme. These findings demonstrate for the first time the ability of a specific C. albicans enzyme to degrade and deactivate a host antimicrobial peptide involved in the protection of the oral mucosa against C. albicans, thereby providing new insights into the factors directing the transition of C. albicans from commensal to pathogen, with important clinical implications for alternative therapy. This report characterizes the first defined mechanism behind the enhanced susceptibility of HIV+ individuals to oral candidiasis since the emergence of HIV.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661360 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005039 | PLOS |
Int J Biol Macromol
January 2025
Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1416634793, Iran; Wound Care Solution, Nano Fanavaran Narin Teb Co., Tehran, P.O. Box 19177-53531, Iran; Physical Chemistry I, Department of Chemistry and Biology & Research Center of Micro and Nanochemistry and Engineering (Cμ), University of Siegen, 57076 Siegen, Germany. Electronic address:
This study reports the development of a highly absorbent Chitosan (CS)/Tannic Acid (TA) sponge, synthesized via chemical cross-linking with Epichlorohydrin (ECH) and integrated with zinc oxide nanoparticles (ZnO NPs) as a novel hemostatic anti-infection agent. The chemical properties of the sponges were characterized using Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and zeta potential measurements. Morphological and elemental analyses conducted through scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDAX) revealed a uniform distribution of ZnO NPs, with particle sizes below 20 nm.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Catalytic Applications Laboratory, Department of Chemistry, School of Basic Sciences, Faculty of Science, Manipal University Jaipur, Dehmi Kalan, Jaipur 303007, Rajasthan, India. Electronic address:
In the present study, biopolymeric Schiff base (SB) ligands were synthesized from chitosan and isatin. Consequently, their earth abundant transition metal complexes of cobalt and copper were synthesized. All compounds were extensively characterized using FTIR and UV spectroscopy, thermo-gravimetric (TG) analysis, X-ray powder diffraction (XRD) and FESEM (field emission scanning electron microscopy).
View Article and Find Full Text PDFJ Mater Chem B
January 2025
Drug Delivery, Disposition, and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Pde, Parkville, VIC, 3052, Australia.
Infections caused by fungal pathogens are a global health problem, and have created an urgent need for new antimicrobial strategies. This report details the synthesis of lipidated 2-vinyl-4,4-dimethyl-5-oxazolone (VDM) oligomers an optimized Cu(0)-mediated reversible-deactivation radical polymerization (RDRP) approach. Cholesterol-Br was used as an initiator to synthesize a library of oligo-VDM (degree of polymerisation = 5, 10, 15, 20, and 25), with an α-terminal cholesterol group.
View Article and Find Full Text PDFJ Med Chem
January 2025
College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, P. R. China.
infection is a major public health problem, exacerbated by the emergence of drug-resistant fungi with the widespread use of antifungal drugs. Therefore, the development of novel antifungal drugs for drug-resistant infections is crucial. We constructed a series of dendritic antifungal peptides (AFPs) with different chain lengths of fatty acids as hydrophobic ends and 2 or 3 protease-stable repeats (Arg-Pro) as dendritic peptide branches.
View Article and Find Full Text PDFPublic health alarm concerning the emerging fungus is fueled by its antifungal drug resistance and propensity to cause deadly outbreaks. Persistent skin colonization drives transmission and lethal sepsis although its basis remains mysterious. We compared the skin colonization dynamics of with its relative , quantifying skin fungal persistence and distribution and immune composition and positioning.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!