Current Perspectives of Antifungal Therapy: A Special Focus on Candida auris.

Candida auris is an emerging Candida sp. that has rapidly spread all over the world. The evidence regarding its origin and emerging resistance is still unclear. The severe infection caused by this species results in significant mortality and morbidity among the elderly and immunocompromised individuals. The development of drug resistance is the major factor associated with the therapeutic failure of existing antifungal agents. Previous studies have addressed the antifungal resistance profile and drug discovery for C. auris. However, complete coverage of this information in a single investigation is not yet available. In this review, we have mainly focused on recent developments in therapeutic strategies against C. auris. Based on the available information, several different approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, synthetic chemicals, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Therefore, we anticipate that the findings gathered in this review will encourage further in vivo studies and clinical trials.

Anti-Candidal Marine Natural Products: A Review.

Candida spp. are common opportunistic microorganisms in the human body and can cause mucosal, cutaneous, and systemic infections, mainly in individuals with weakened immune systems. Candida albicans is the most isolated and pathogenic species; however, multi-drug-resistant yeasts like Candida auris have recently been found in many different regions of the world. The increasing development of resistance to common antifungals by Candida species limits the therapeutic options. In light of this, the present review attempts to discuss the significance of marine natural products in controlling the proliferation and metabolism of C. albicans and non-albicans species. Natural compounds produced by sponges, algae, sea cucumber, bacteria, fungi, and other marine organisms have been the subject of numerous studies since the 1980s, with the discovery of several products with different chemical frameworks that can inhibit Candida spp., including antifungal drug-resistant strains. Sponges fall under the topmost category when compared to all other organisms investigated. Terpenoids, sterols, and alkaloids from this group exhibit a wide array of inhibitory activity against different Candida species. Especially, hippolide J, a pair of enantiomeric sesterterpenoids isolated from the marine sponge Hippospongia lachne, exhibited strong activity against Candida albicans, Candida parapsilosis, and Candida glabrata. In addition, a comprehensive analysis was performed to unveil the mechanisms of action and synergistic activity of marine products with conventional antifungals. In general, the results of this review show that the majority of chemicals derived from the marine environment are able to control particular functions of microorganisms belonging to the Candida genus, which can provide insights into designing new anti-candidal therapies.

Ecological risk assessment of metals in the Arctic environment with emphasis on Kongsfjorden Fjord and freshwater lakes of Ny-Ålesund, Svalbard.

The concentrations of five heavy metals (Cd, Cr, Cu, Pb, and Zn) in the sediments, water, phytoplankton, zooplankton, and macroalgae from Kongsfjorden Fjord and the freshwater lakes of Ny-Ålesund in the Svalbard archipelago were determined in order to describe the anthropogenic impacts related to the Ny-Ålesund town. Water samples from nine stations, sediment samples from 23 stations, plankton samples from five stations, and six species of macroalgae were collected and subjected to heavy metal analysis using atomic absorption spectrophotometry (AAS). Only Cu and Zn were detected in the water samples. The plankton samples had only Zn, Cu, and Cr. The average metal concentrations in macroalgae fell in the decreasing order of Cu > Zn > Cr > Cd > Pb. In sediment samples, the metal order was as follows: Zn > Cu > Cr > Pb > Cd. Multivariate statistical analyses including principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to identify the source of the metal contamination. The metals were found to originate from a blend of both anthropogenic and geogenic sources. Pollution monitoring indices including geoaccumulation index (Igeo), contamination factor, contamination degree (Cdeg), pollution load index (PLI), and potential ecological risk (PER) were calculated using the metal data. In the study area, Igeo values of the metals showed pollution grades from 0 (uncontaminated) to 6 (extremely contaminated). Cdeg fell in classes from 1 (low contamination) to 4 (very high contamination). PLI values ranged between 0 and 5.68. PER values expressed that except for a few stations located at higher elevations in the glacial outwash plains, all other sites were highly polluted. The high level of pollution indices in the sites can be attributed to the anthropogenic activities persistent in the study area.

Metal-associated human health risk assessment due to consumption of pelagic and benthic ichthyofaunal resources from the highly contaminated Cuddalore coast in Southern India.

We present seasonal variation of four metals (Cd, Cu, Pb, and Zn) in nine pelagic and three benthic fish species from the highly polluted Cuddalore coast in Tamil Nadu, India. Metals were assessed using atomic absorption spectrometry and detected in all fish species, in at least one season, except Iniistius cyanifrons where cadmium was not detected throughout. In both benthic and pelagic fish, order of metal concentration was Zn > Cu > Pb > Cd. Multivariate statistical analysis revealed that metals may have originated from both natural and anthropogenic sources. Health risk assessment revealed that consumption of fish from Cuddalore coast does not pose health risk for now; however, hazard index values (pelagic = 0.97; benthic = 0.90) are in borderline. Even a slight increase in metal concentration in fish can prove hazardous for human consumption. Sooner or later, eating fish from Cuddalore coast may pose a considerable health risk to humans if metal pollution is not held at Bay.

Assessment of renal and hepatic dysfunction by co-exposure to toxic metals (Cd, Pb) and fluoride in people living nearby an industrial zone.

Togo's phosphate processing plant at Kpeme discharges waste, containing Cd, Pb, and fluoride, into the sea and on the soil. Heavy metals toxicity on kidneys and the liver has been studied. However, fluoride toxicity on these organs remains to be investigated. The present study deals with the variation in renal and hepatic functioning parameters due to fluoride, Cd and Pb. Totally, 350 volunteers were recruited from five different localities around this phosphate processing plant for sample collection. Cd and Pb contents in blood samples were determined by spectrophotometry and fluoride by the titanium chloride method. Biochemical parameters were measured using Biolab kits. The pollutant contents were elevated in polluted areas where ASAT, ALAT, creatinine, and urea increased, and total protein decreased. Correlation and multivariate tests showed that fluoride is related to the various pathologies mentioned. PCA revealed that phosphate processing in Togo is a source of renal and hepatic toxicity.

Metal accumulation and biomineralisation of coastal and mangrove-associated molluscs of Palk Bay, Southeastern India.

The present study aimed to determine metal accumulation levels in tissue and biomineralisation in shells of 20 species of molluscs (13 gastropods and 7 bivalves) from Palk Bay, India. In most cases, metal concentrations in the tissues were higher than in the shells of the same species collected from same location, meaning that in many cases biomineralisation factors of metal ratios were <1. The highest biomineralisation factor for Cd was detected in Melampus sincaporensis (3.72 ± 0.1) from the Thondi mangrove, for Pb in Cerithidea cingulata (2.51 ± 0.17) from the Vattanam mangrove, for Cu in Melampus sincaporensis (0.88 ± 0.2) from the Thondi mangrove, and for Zn in Cerithidea cingulata (0.93 ± 0.3) from the Devipattinam mangrove. In most cases, metal concentrations were higher than reported in previous studies but were within the maximum limits stated by national and international regulatory agencies. Variations in the biomineralisation factor of metal ratios among the molluscan species likely stems from variations in bioaccumulation efficiency, selectivity of individual organisms, and availability of metals in the mangrove and coastal environments.

In Vitro and In Silico Analysis of Ascorbic Acid Towards Lanosterol 14-α-Demethylase Enzyme of Fluconazole-Resistant Candida albicans.

Antibiotic resistance is one of the major concerns and the biggest threats to the world population. The incidents of antibiotic resistance in Candida spp. were frequently recorded. In the present investigation, antifungal potential of ascorbic acid (AA) was evaluated. According to the in vitro analysis, the zone of inhibition of AA (24.75 ± 0.35 mm) against C. albicans was greater as compared to other vitamins tested. AA significantly modulate the growth of C. albicans at 25 mg/ml. The highest percentage (94.67%) of cell viability was observed in untreated cells, and low cell viability (29.36%) was observed in cells treated with 50 mg/ml of AA (2 × MIC). Further, AO/EB (acridine orange/ethidium bromide), propidium iodide staining, and real-time qPCR confirmed the loss of membrane integrity due to membrane lesions that caused cell death. Lanosterol 14-α-demethylase (L-14α-DM) is the product of ERG11 and acted as superior drug target of C. albicans. Molecular docking analysis confirmed that active interaction of ascorbic acid with L-14α-DM. Based on the present investigation, the efficiency of AA was effectively proved through the in vitro and in silico analysis. This finding has evidenced the effectiveness of AA as a potential candidate against C. albicans.

Tailoring Cu substituted hydroxyapatite/functionalized multiwalled carbon nanotube composite coating on 316L SS implant for enhanced corrosion resistance, antibacterial and bioactive properties.

The aim of the present work is to study the potential change in the antibacterial properties of Cu-hydroxyapatite/functionalized multiwall carbon nanotube (HA/f-MWCNT) composite coated heterogeneous implant surfaces against Gram positive and Gram-negative microorganism and to reveal the possible contribution of surface corrosion effects arising in stimulated body fluid. Novel spray pyrolysis instrument designed with double nozzle was used for the fabrication of Cu-hydroxyapatite/f-MWCNT film on 316L stainless steel (SS). The Cu-hydroxyapatite/MWCNT coated bioimplant was characterized by a series of techniques to identify the crystallinity, chemical bonds, surface morphology and elemental composition. The results disclose that the coated implants exhibit highly crystalline nature with the space group of P63mc and spherical shaped morphology. The corrosion current density revealed a remarkable decrease from 6.8 to 3.8 µA suggesting that the Cu substituted hydroxyapatite/f-MWCNT composite coating provided higher barrier properties which is beneficial to achieve higher corrosion protection of 316L SS implant. The hybrid Cu-hydroxyapatite-MWCNT composite revealed better antibacterial ability than HA/MWCNT for both gram positive and gram-negative bacteria with a maximum inhibition zone of 13-17 mm, compared with hydroxyapatite/f-MWCNT. The antibacterial ability of the Cu-hydroxyapatite/f-MWCNT nanocomposites was effective against Escherichia coli compared with other microorganisms. The Cu-hydroxyapatite/f-MWCNT nanocomposite exhibited that the coated material is nontoxic, biocompatible and suitable for biomedical application.

New insight of red seaweed derived Callophycin A as an alternative strategy to treat drug resistance vaginal candidiasis.

Marine natural products are recognised as one among the major contributors of several important biological functions. The arguments has made to utilization of natural products against different kinds of infectious diseases. In the present study, Callophycin A was successfully prepared and its anti-candidal activity was evaluated through in-vitro and in-vivo methods. The in-vitro results revealed that, Callophycin A significantly inhibits the azole resistant and sensitive C. albicans. Further, in-vivo animal experiments have shown the effective reduction in CFU of C. albicans from its beginning day of the treatment as compared to the disease control group. At the end of Callophycin A administration, there was a decrease in inflammatory response and immune molecules such as IL-6, IL-12, IL-17, IL-22, TNF-α, macrophages, CD4 and CD8 cells were observed. Whereas the animals in the disease control group expressed all the parameters with the elevated level as compared to the control group. There are no hematological abnormalities such as neutropenia, lymphocytosis and eosinophilia was observed in any animal groups except the disease control group. Finally, the evidence based prediction of anti-candidal efficacious of Callophycin A was demonstrated.

Antifungal susceptibility and virulence profile of candida isolates from abnormal vaginal discharge of women from southern India.

OBJECTIVE: Vaginal candidiasis is the most common opportunistic fungal infection, largely associated with a woman's psychological and economic status. Recently, the rate of disease progression has increased extensively; however, region-specific studies are very limited. This study aimed to understand variation in hydrolytic activities and antifungal susceptibility of Candida isolates from vaginal discharge. STUDY DESIGN: The present study was aimed to understand the variation of hydrolytic activities and antifungal susceptibility of Candida isolates from vaginal discharge. RESULTS: In total, 34 different Candida isolates were collected: C. albicans (n = 17; 50 %), C. glabrata (n = 6; 17.64 %), C. tropicalis (n = 4; 11.76 %) and C. parapsilosis (n = 7; 20.58 %). All isolates were primarily identified and confirmed by basic microbiological methods followed by the VITEK-2 system. Antifungal susceptibility of the isolates were evaluated using yeast antifungal susceptibility testing cards. The isolates of C. albicans, C. glabrata, C. tropicalis and C. parapsilosis were 100 % susceptible to amphotericin B. The non-albicans isolates presented 100 % of proteolytic and lipolytic activity compared with C. albicans. Eight (47.06 %) C. albicans isolates showed positive esterase activity (Pz<1), whereas nine (52.94 %) were negative to esterase (Pz = 1). Of the 34 Candida isolates, 28 (82.35 %) were found to be moderate-to-strong biofilm producers: 14 C. albicans, three C. glabrata, six C. parapsilosis and five C. tropicalis. CONCLUSION: This study clarified the antifungal susceptibility and virulence behaviour of Candida isolates; this will be of use in the selection of antifungal agents for Candida prophylaxis.

Heavy metals accumulation in seagrasses collected from Palk Bay, South-eastern India.

Metals such as Cd, Pb, Cu and Zn were analysed in five seagrass species from five locations of the Palk Bay coast of south-eastern India. The maximum Cd concentration (2.83 ± 0.08 µg g-1) was recorded in Syringodium isoetifolium on the Mallipattinam coast in the post-monsoon season, and the Cu (29.54 ± 1.03 µg g-1) in Enhalus acoroides of the Thondi coast during monsoon season. The maximum concentrations of Pb (3.12 ± 0.14 µg g-1) and Zn (52.66 ± 0.88 µg g-1) were observed in S. isoetifolium and Cymodoceae rotundata on the Devipattinam and Karangadu coasts, respectively, during the monsoon season. The metal concentrations obtained in different seagrass species varied significantly among species, and no clear monsoon season had a clear effect on the accumulation of heavy metals in the investigated seagrass species. S. isoetifolium has higher capacity for Cd and Pb accumulation than other tested seagrass species.

Multivariate statistical and GIS-based approaches for toxic metals in tropical mangrove ecosystem, southeast coast of India.

The heavy metal concentrations in water and sediment samples were investigated in the tropical Muthupet mangrove ecosystem, southeast coast of India. The results demonstrated that, ranges of metals in water comprise of Cd-0.05 to 3.72; Cu-0.5 to 4.43; Pb-6.31 to 17.87; Zn-0.0 to12.91 ppm and sediment comprises of Cd-0.06 to 0.57; Cu-4.46 to 20.59; Pb-2.90 to 21.35; Zn-4.41 to 39.18 ppm. In all the three sites, heavy metals in sediment exhibited significant higher concentrations compared to water, except Cd. The spatial distribution of metals in water and sediment samples followed a similar pattern except Cd with the preponderance of Zn (75% of total metals) followed by Cu and Pb. Muller's Geoaccumulation indexes (Igeo) showed Cd is a potent pollutant in the ecosystem and moderately contaminated the study area. The aquaculture and agricultural culture practices follow improper disposal of municipal wastages, and idol immersion activities are the potent metallic sources for heavy metal pollution were identified by performing principle component analysis. In order to protect the ecosystem from further contamination, regular monitoring is needed to in order to control the anthropogenic discharges. Graphical abstract.