Candida albicans is the primary etiological agent associated with candidiasis in humans. Unrestricted growth of C. albicans can progress to systemic infections in the worst situation. This study investigates the antifungal activity of Hydroxychloroquine (HCQ) and mode of action against C. albicans. HCQ inhibited the planktonic growth and yeast to hyphal form morphogenesis of C. albicans significantly at 0.5 mg/ml concentration. The minimum inhibitory concentrations (MIC(50)) of HCQ for C. albicans adhesion and biofilm formation on the polystyrene surface was at 2 mg/ml and 4 mg/ml respectively. Various methods, such as scanning electron microscopy, exploration of the ergosterol biosynthesis pathway, cell cycle analysis, and assessment of S oxygen species (ROS) generation, were employed to investigate HCQ exerting its antifungal effects. HCQ was observed to reduce ergosterol levels in the cell membranes of C. albicans in a dose-dependent manner. Furthermore, HCQ treatment caused a substantial arrest of the C. albicans cell cycle at the G0/G1 phase, which impeded normal cell growth. Gene expression analysis revealed upregulation of SOD2, SOD1, and CAT1 genes after HCQ treatment, while genes like HWP1, RAS1, TEC1, and CDC 35 were downregulated. The study also assessed the in vivo efficacy of HCQ in a mice model, revealing a reduction in the pathogenicity of C. albicans after HCQ treatment. These results indicate that HCQ holds for the development of novel antifungal therapies.
Two strictly aerobic, Gram-staining-positive, non-spore-forming,
regular rod-shaped (approximately 0.7 × 1.9 mm)
bacteria (HY170T and HY001) were isolated from bat feces
collected from Chongzuo city, Guangxi province (22°2054N,
106°4920E, July 2011) and Chuxiong Yi Autonomous Prefecture,
Yunnan province (25°0910N, 102°0439E, October
2013) of South China, respectively. Optimal growth is obtained
at 25–28°C (range, 4–32°C) on BHI-5% sheep blood
plate with pH 7.5 (range, 5.0–10.0) in the presence of 0.5–
1.0% NaCl (w/v) (range, 0–15% NaCl [w/v]). The phylogenetic
and phylogenomic trees based respectively on the 16S
rRNA gene and 845 core gene sequences revealed that the
two strains formed a distinct lineage within the genus Brevibacterium,
most closely related to B. aurantiacum NCDO
739T (16S rRNA similarity, both 98.5%; dDDH, 46.7–46.8%;
ANI, 91.9–92.1%). Strain HY170T contained MK-8(H2), diphosphatidylglycerol
(DPG) and phosphatidylglycerol (PG),
galactose and ribose as the predominant menaquinone, major
polar lipids, and main sugars in the cell wall teichoic acids,
respectively. The meso-diaminopimelic acid (meso-DAP)
was the diagnostic diamino acid of the peptidoglycan found
in strain HY170T. Anteiso-C15:0 and anteiso-C17:0 were the
major fatty acids (> 10%) of strains HY170T and HY001, with
anteiso-C17:1A predominant in strain HY170T but absent in
strain HY001. Mining the genomes revealed the presence
of secondary metabolite biosynthesis gene clusters encoding
for non-alpha poly-amino acids (NAPAA), ectoine, siderophore,
and terpene. Based on results from the phylogenetic,
chemotaxonomic and phenotypic analyses, the two strains
could be classified as a novel species of the genus Brevibacterium,
for which the name Brevibacterium zhoupengii sp.
nov. is proposed (type strain HY170T = CGMCC 1.18600T
= JCM 34230T).
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which suggested that the influence of ethnic differences should
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