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In vitro studies on oxidative stress-independent, Ag nanoparticles-induced cell toxicity of Candida albicans, an opportunistic pathogen.

ABSTRACT: Silver nanoparticles (AgNps) have attracted maximal attention among all metal nanoparticles, and the study of their biological properties has gained impetus for further medical adoption. This study evaluated the cellular and molecular mechanisms associated with the action of AgNps against an opportunistic pathogen, Candida albicans. Spherical, stable AgNp (average size 21.6 nm) prepared by a chemical reduction method showed minimum inhibitory concentration (required to inhibit the growth of 90% of organisms) at 40 ?g/mL. AgNps have been reported to induce oxidative stress-mediated programmed cell death through the accumulation of intracellular reactive oxygen species (ROS). However, this study demonstrated that intracellular levels of AgNp-induced ROS could be reversed by using antioxidant ascorbic acid, but the sensitivity of AgNp-treated Candida cells could not be completely reversed. Moreover, in addition to the generation of ROS, the AgNps were found to affect other cellular targets resulting in altered membrane fluidity, membrane microenvironment, ergosterol content, cellular morphology, and ultrastructure. Thus, the generation of ROS does not seem to be the sole major cause of AgNp-mediated cell toxicity in Candida. Rather, the multitargeted action of AgNps, generation of ROS, alterations in ergosterol content, and membrane fluidity together seem to have potentiated anti-Candida action. Thus, this "nano-based drug therapy" is likely to favor broad-spectrum activity, multiple cellular targets, and minimum host toxicity. AgNps, therefore, appear to have the potential to address the challenges in multidrug resistance and fungal therapeutics.

SUBMITTER: Radhakrishnan VS

PROVIDER: S-EPMC5863646 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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In vitro studies on oxidative stress-independent, Ag nanoparticles-induced cell toxicity of <i>Candida albicans</i>, an opportunistic pathogen.

Radhakrishnan Venkatraman Srinivasan VS Dwivedi Surya Prakash SP Siddiqui Mohammed Haris MH Prasad Tulika T

International journal of nanomedicine 20180315 T-NANO 2014 Abstracts

Silver nanoparticles (AgNps) have attracted maximal attention among all metal nanoparticles, and the study of their biological properties has gained impetus for further medical adoption. This study evaluated the cellular and molecular mechanisms associated with the action of AgNps against an opportunistic pathogen, <i>Candida albicans</i>. Spherical, stable AgNp (average size 21.6 nm) prepared by a chemical reduction method showed minimum inhibitory concentration (required to inhibit the growth ...[more]

PMID: 29593404

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Project description:BACKGROUND:Opportunistic yeast pathogens of the genus Candida are an important medical problem. Candida albicans, the most prevalent Candida species, is a natural commensal of humans that can adopt a pathogenic behavior. This species is highly heterozygous and cannot undergo meiosis, adopting instead a parasexual cycle that increases genetic variability and potentially leads to advantages under stress conditions. However, the origin of C. albicans heterozygosity is unknown, and we hypothesize that it could result from ancestral hybridization. We tested this idea by analyzing available genomes of C. albicans isolates and comparing them to those of hybrid and non-hybrid strains of other Candida species. RESULTS:Our results show compelling evidence that C. albicans is an evolved hybrid. The genomic patterns observed in C. albicans are similar to those of other hybrids such as Candida orthopsilosis MCO456 and Candida inconspicua, suggesting that it also descends from a hybrid of two divergent lineages. Our analysis indicates that most of the divergence between haplotypes in C. albicans heterozygous blocks was already present in a putative heterozygous ancestor, with an estimated 2.8% divergence between homeologous chromosomes. The levels and patterns of ancestral heterozygosity found cannot be fully explained under the paradigm of vertical evolution and are not consistent with continuous gene flux arising from lineage-specific events of admixture. CONCLUSIONS:Although the inferred level of sequence divergence between the putative parental lineages (2.8%) is not clearly beyond current species boundaries in Saccharomycotina, we show here that all analyzed C. albicans strains derive from a single hybrid ancestor and diverged by extensive loss of heterozygosity. This finding has important implications for our understanding of C. albicans evolution, including the loss of the sexual cycle, the origin of the association with humans, and the evolution of virulence traits.

Project description:UnlabelledClathrin-mediated endocytosis (CME) is conserved among eukaryotes and has been extensively analyzed at a molecular level. Here, we present an analysis of CME in the human fungal pathogen Candida albicans that shows the same modular structure as those in other fungi and mammalian cells. Intriguingly, C. albicans is perfectly viable in the absence of Arp2/3, an essential component of CME in other systems. In C. albicans, Arp2/3 function remains essential for CME as all 15 proteins tested that participate in CME, including clathrin, lose their characteristic dynamics observed in wild-type (WT) cells. However, since arp2/3 cells are still able to endocytose lipids and fluid-phase markers, but not the Ste2 and Mup1 plasma membrane proteins, there must be an alternate clathrin-independent pathway we term Arp2/3-independent endocytosis (AIE). Characterization of AIE shows that endocytosis in arp2 mutants relies on actin cables and other Arp2/3-independent actin structures, as inhibition of actin functions prevented cargo uptake in arp2/3 mutants. Transmission electron microscopy (TEM) showed that arp2/3 mutants still formed invaginating tubules, cell structures whose proper functions are believed to heavily rely on Arp2/3. Finally, Prk1 and Sjl2, two proteins involved in patch disassembly during CME, were not correctly localized to sites of endocytosis in arp2 mutants, implying a role of Arp2/3 in CME patch disassembly. Overall, C. albicans contains an alternative endocytic pathway (AIE) that relies on actin cable function to permit clathrin-independent endocytosis (CIE) and provides a system to further explore alternate endocytic routes that likely exist in fungal species.ImportanceThere is a well-established process of endocytosis that is generally used by eukaryotic cells termed clathrin-mediated endocytosis (CME). Although the details are somewhat different between lower and higher eukaryotes, CME appears to be the dominant endocytic process in all eukaryotes. While fungi such as Saccharomyces cerevisiae have proven excellent models for dissecting the molecular details of endocytosis, loss of CME is so detrimental that it has been difficult to study alternate pathways functioning in its absence. Although the fungal pathogen Candida albicans has a CME pathway that functions similarly to that of S. cerevisiae, inactivation of this pathway does not compromise growth of yeast-form C. albicans. In these cells, lipids and fluid-phase molecules are still endocytosed in an actin-dependent manner, but membrane proteins are not. Thus, C. albicans provides a powerful model for the analysis of CME-independent endocytosis in lower eukaryotes.

Dataset Information

In vitro studies on oxidative stress-independent, Ag nanoparticles-induced cell toxicity of Candida albicans, an opportunistic pathogen.

Publications

In vitro studies on oxidative stress-independent, Ag nanoparticles-induced cell toxicity of <i>Candida albicans</i>, an opportunistic pathogen.

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