RAD51-WSS1-dependent genetic pathways are essential for DNA-protein crosslink repair and pathogenesis in Candida albicans.

Genetic analyses in Saccharomyces cerevisiae suggest that nucleotide excision repair (NER), homologous recombination (HR), and protease-dependent repair pathways coordinately function to remove DNA-protein crosslinks (DPCs) from the genome. DPCs are genomic cytotoxic lesions generated because of the covalent linkage of proteins with DNA. Although NER and HR processes have been studied in pathogenic Candida albicans, their roles in DPC repair (DPCR) are yet to be explored. Proteases like Wss1 and Tdp1 (tyrosyl-DNA phosphodiesterase-1) are known to be involved in DPCR; however, Tdp1 that selectively removes topoisomerase-DNA complexes is intrinsically absent in C. albicans. Therefore, the mechanism of DPCR might have evolved differently in C. albicans. Herein, we investigated the interplay of three genetic pathways and found that RAD51-WSS1-dependent HR and protease-dependent repair pathways are essential for DPC removal, and their absence caused an increased rate of loss of heterozygosity in C. albicans. RAD1 but not RAD2 of NER is critical for DPCR. In addition, we observed truncation of chromosome #6 in the cells defective in both RAD51 and WSS1 genes. While the protease and DNA-binding activities are essential, a direct interaction of Wss1 with the eukaryotic DNA clamp proliferating cell nuclear antigen is not a requisite for the function of Wss1. DPCR-defective C. albicans cells exhibited filamentous morphology, reduced immune cell evasion, and attenuation in virulence. Thus, we concluded that RAD51-WSS1-dependent DPCR pathways are essential for genome stability and candidiasis development. Since no vaccine against candidiasis is available for human use yet, we propose to explore DPCR-defective attenuated strains (rad51ΔΔwss1ΔΔ and rad2ΔΔrad51ΔΔwss1ΔΔ) for whole-cell vaccine development.

Benzimidazole and piperidine containing novel 1,2,3-triazole hybrids as anti-infective agents: Design, synthesis, in silico and in vitro antimicrobial efficacy.

Cu alkyne-azide cycloaddition was used to easily synthesize a library of novel heterocycles containing benzimidazole and piperidine based 1,2,3-triazole(7a-7l) derivatives. The synthesized analogs were characterized by various spectroscopic techniques like FTIR, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and mass spectrometry. All these novel bioactive compounds (7a-7l) were evaluated for in vitro antibacterial and antifungal efficacy. Compound 7k exhibited appreciable potent activity against Escherichia coli strain. Compounds 7a, 7b, 7f, and 7i showed excellent potent activity against all bacterial strains. Compound 7b, 7c, 7d, and 7g derivatives showed excellent effects when tested in vitro for antifungal activity against various fungal strains. Additionally, a molecular docking investigation revealed that compound 7k has the ability to bind to the active site of the E. coli DNA gyrase subunit protein and form hydrogen bonds with significant amino acid residues Asp73 and Asp49 in the active sites. In a 100 ns molecular dynamics simulation, the E. coli DNA gyrase protein's steady capacity to bind compound 7k was shown by the low measured root mean square deviation, which was an indication of the complex's conformational stability.

Synthesis, molecular docking, ADME study, and antimicrobial potency of piperazine based cinnamic acid bearing coumarin moieties as a DNA gyrase inhibitor.

A series of novel piperazine based cinnamic acid bearing coumarin derivatives were designed and synthesized by piperazine based cinnamic acids esterification with 4-hydroxycoumarin and characterized by various spectral techniques like infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and mass. The novel bioactive compounds (7a-7m) screen their potential against different bacterial and fungal strains. Compound 7g (minimum inhibitory concentration [MIC] = 12.5 µg/ml) exhibited potent antibacterial activity against Escherichia coli strain. Compounds 7d, 7f, 7g, 7k, 7l, and 7m showed potent antibacterial activity against all bacterial strains. Compounds 7a, 7g, 7h, 7k, 7l, and 7m exhibited potent antifungal activity against all fungal strains. Furthermore, a molecular docking study revealed that compounds 7d, 7f, 7g, and 7k could bind to the active site of E. coli DNA gyrase subunit B protein and form hydrogen bonding with crucial amino acid residues Arg136 in the active sites. Comprehensively, our study recommends that 7d, 7f, 7g, and 7k could be a promising lead for developing more efficient antimicrobial drug candidates and DNA gyrase inhibitors.

Design and synthesis of pyrrolo[2,3-d]pyrimidine linked hybrids as α-amylase inhibitors: molecular docking, MD simulation, ADMET and antidiabetic screening.

Novel pyrrolo[2,3-d]pyrimidine-based analogues were designed, synthesized, and evaluated for their ability to inhibit the α-amylase enzyme in order to treat diabetes. In vitro antidiabetic analysis demonstrated excellent antidiabetic action for compounds 5b, 6c, 7a, and 7b, with IC50 values in the 0.252-0.281 mM range. At a 200 µg/mL concentration, the exceptional percent inhibition values for compounds 5a, 5b, 5d, and 6a varied from 97.79 ± 2.86% to 85.56 ± 4.13% overperforming the standard (acarbose). Molecular docking of all compounds performed with Bacillus paralicheniformis α-amylase enzyme. The most active compounds via in vitro and non-toxic via in silico ADMET and molecular docking analysis, hybrids 6c, 7a, and 7b displayed binding affinity from - 8.2 and - 8.5 kcal/mol. Molecular dynamic simulations of most active compound 5b and 7a investigated into the active sites of the Bacillus paralicheniformis α-amylase enzyme for a 100-ns indicating the stability of hybrid-protein complex. Consistent RGyr values for the two complexes under study further suggest that the system's proteins are closely packed in the dynamic state. Synthesized analogs' in vitro biological assessments, ADMET, molecular docking, and MD modelling reveal that 5b, 6c, 7a, and 7b hybrid analogs may be employed in the development of future antidiabetic drugs.

Chrysin based pyrimidine-piperazine hybrids: design, synthesis, in vitro antimicrobial and in silico E. coli topoisomerase II DNA gyrase efficacy.

Ten chrysin-based pyrimidine-piperazine hybrids have been evaluated in vitro for antimicrobial activity against eleven bacterial and two fungal strains. All compounds 5a-j exhibited moderate to good inhibition, with MIC values ranging from 6.25 to 250 µg/ml. At 6.25 µg/ml and 12.5 µg/ml MIC values, respectively, compounds 5b and 5h demonstrated the most promising potency against E. coli, outperforming ampicillin, chloramphenicol, and ciprofloxacin. None of the substances had the same level of action as norfloxacin. 5a, 5d, 5g, 5h, and 5i have exhibited superior antifungal efficacy than Griseofulvin against C. albicans with 250 µg/ml MIC. All the compounds were also individually docked into the E. coli DNA gyrase ATP binding site (PDB ID: 1KZN) and CYP51 inhibitor (PDB ID: 5V5Z). The most active compound, 5h and 5g displayed a Glide docking score of - 5.97 kcal/mol and - 10.99 kcal/mol against DNA gyrase and 14α-demethylase enzyme CYP51 respectively. Potent compounds 5b, 5h, and 5g may be used to design new, innovative antimicrobial agents, according to in vitro, ADMET, and in silico biological efficacy analyses.

Interdomain connecting loop and J loop structures determine cross-species compatibility of PCNA.

Eukaryotic proliferating cell nuclear antigen (PCNA) plays an essential role in orchestrating the assembly of the replisome complex, stimulating processive DNA synthesis, and recruiting other regulatory proteins during the DNA damage response. PCNA and its binding partner network are relatively conserved in eukaryotes, and it exhibits extraordinary structural similarity across species. However, despite this structural similarity, the PCNA of a given species is rarely functional in heterologous systems. In this report, we determined the X-ray crystal structure of Neurospora crassa PCNA (NcPCNA) and compared its structure-function relationship with other available PCNA studies to understand this cross-species incompatibility. We found two regions, the interdomain connecting loop (IDCL) and J loop structures, vary significantly among PCNAs. In particular, the J loop deviates in NcPCNA from that in Saccharomyces cerevisiae PCNA (ScPCNA) by 7 Å. Differences in the IDCL structures result in varied binding affinities of PCNAs for the subunit Pol32 of DNA polymerase delta and for T2-amino alcohol, a small-molecule inhibitor of human PCNA. To validate that these structural differences are accountable for functional incompatibility in S. cerevisiae, we generated NcPCNA mutants mimicking IDCL and J loop structures of ScPCNA. Our genetic analyses suggested that NcPCNA mutants are fully functional in S. cerevisiae. The susceptibility of the strains harboring ScPCNA mimics of NcPCNA to various genotoxic agents was similar to that in yeast cells expressing ScPCNA. Taken together, we conclude that in addition to the overall architecture of PCNA, structures of the IDCL and J loop of PCNA are critical determinants of interspecies functional compatibility.

'PIPs' in DNA polymerase: PCNA interaction affairs.

Interaction of PCNA with DNA polymerase is vital to efficient and processive DNA synthesis. PCNA being a homotrimeric ring possesses three hydrophobic pockets mostly involved in an interaction with its binding partners. PCNA interacting proteins contain a short sequence of eight amino acids, popularly coined as PIP motif, which snuggly fits into the hydrophobic pocket of PCNA to stabilize the interaction. In the last two decades, several PIP motifs have been mapped or predicted in eukaryotic DNA polymerases. In this review, we summarize our understandings of DNA polymerase-PCNA interaction, the function of such interaction during DNA synthesis, and emphasize the lacunae that persist. Because of the presence of multiple ligands in the replisome complex and due to many interaction sites in DNA polymerases, we also propose two modes of DNA polymerase positioning on PCNA required for DNA synthesis to rationalize the tool-belt model of DNA replication.

Virulence and pathogenicity of a Candida albicans mutant with reduced filamentation.

Deletion of DNA polymerase eta (Rad30/Polη) in pathogenic yeast Candida albicans is known to reduce filamentation induced by serum, ultraviolet, and cisplatin. Because nonfilamentous C. albicans is widely accepted as avirulent form, here we explored the virulence and pathogenicity of a rad30Δ strain of C. albicans in cell-based and animal systems. Flow cytometry of cocultured fungal and differentiated macrophage cells revealed that comparatively higher percentage of macrophages was associated with the wild-type than rad30Δ cells. In contrast, higher number of Polη-deficient C. albicans adhered per macrophage membrane. Imaging flow cytometry showed that the wild-type C. albicans developed hyphae after phagocytosis that caused necrotic death of macrophages to evade their clearance. Conversely, phagosomes kill the fungal cells as estimated by increased metacaspase activity in wild-type C. albicans. Despite the morphological differences, both wild-type and rad30∆ C. albicans were virulent with a varying degree of pathogenicity in mice models. Notably, mice with Th1 immunity were comparatively less susceptible to systemic fungal infection than Th2 type. Thus, our study clearly suggests that the modes of interaction of morphologically different C. albicans strains with the host immune cells are diverged, and host genetic background and several other attributing factors of the fungus could additionally determine their virulence.

Multifaceted activities of DNA polymerase η: beyond translesion DNA synthesis.

DNA polymerases are evolved to extend the 3'-OH of a growing primer annealed to a template DNA substrate. Since replicative DNA polymerases have a limited role while replicating structurally distorted template, translesion DNA polymerases mostly from Y-family come to the rescue of stalled replication fork and maintain genome stability. DNA polymerase eta is one such specialized enzyme whose function is directly associated with casual development of certain skin cancers and chemo-resistance. More than 20 years of extensive studies are available to support TLS activities of Polη in bypassing various DNA lesions, in addition, limited but crucial growing evidence also exist to suggest Polη possessing TLS-independent cellular functions. In this review, we have mostly focused on non-TLS activities of Polη from different organisms including our recent findings from pathogenic yeast Candida albicans.

Molecular modeling and biological investigation of novel s-triazine linked benzothiazole and coumarin hybrids as antimicrobial and antimycobacterial agents.

A novel series of s-triazine linked benzothiazole and coumarin hybrids (6a-6d, 7a-7d, and 8a-8d) were synthesized and characterized by IR, NMR, and mass spectrometry. The compound's in vitro antibacterial and antimycobacterial activities were also evaluated. Remarkable antibacterial activity with MIC in the range of 12.5-62.5 µM and antifungal activity of 100-200 µM were demonstrated by in vitro antimicrobial analysis. Compounds 6b, 6d, 7b, 7d, and 8a strongly inhibited all bacterial strains, while 6b, 6c, and 7d had good to moderate efficacy against M. tuberculosis H37Rv. Synthesized hybrids are observed in the active pocket of the S. aureus dihydropteroate synthetase enzyme, according to a molecular docking investigations. Among the docked compounds, 6d had a strong interaction and a greater binding affinity, and the dynamic stability of protein-ligand complexes was examined using molecular dynamic simulation with various settings at 100 ns. The proposed compounds successfully maintained their molecular interaction and structural integrity inside the S. aureus dihydropteroate synthase, according to the MD simulation analysis. These in silico analyses supported the in vitro antibacterial results of compound 6d, which demonstrated outstanding in vitro antibacterial efficacy against all bacterial strains. In the quest for new antibacterial drug-like molecules, compounds 6d, 7b, and 8a have been identified as promising lead compounds.Communicated by Ramaswamy H. Sarma.

Immunogenicity and efficacy of CNA25 as a potential whole-cell vaccine against systemic candidiasis.

Disseminated fungal infections account for ~1.5 million deaths per year worldwide, and mortality may increase further due to a rise in the number of immunocompromised individuals and drug-resistance fungal species. Since an approved antifungal vaccine is yet to be available, this study explored the immunogenicity and vaccine efficacy of a DNA polymerase mutant strain of Candida albicans. CNA25 is a pol32ΔΔ strain that exhibits growth defects and does not cause systemic candidiasis in mice. Immunized mice with live CNA25 were fully protected against C. albicans and C. parapsilosis but partially against C. tropicalis and C. glabrata infections. CNA25 induced steady expression of TLR2 and Dectin-1 receptors leading to a faster recognition and clearance by the immune system associated with the activation of protective immune responses mostly mediated by neutrophils, macrophages, NK cells, B cells, and CD4+ and CD8+ T cells. Molecular blockade of Dectin-1, IL-17, IFNγ, and TNFα abolished resistance to reinfection. Altogether, this study suggested that CNA25 collectively activates innate, adaptive, and trained immunity to be a promising live whole-cell vaccine against systemic candidiasis.

Synthesis, characterization, molecular dynamic simulation, and biological assessment of cinnamates linked to imidazole/benzimidazole as a CYP51 inhibitor.

A class of 2-(1H-imidazol-1-yl)-1-phenylethyl cinnamates 6a-6j and 2-(1H-benzo[d]imidazol-1-yl)-1-phenylethyl cinnamates 7a-7j were synthesized, and their synthesis was validated using various spectroscopic techniques like IR, NMR, and Mass spectrometry. In addition, the compounds were assessed for in-vitro antibacterial against gram-positive and gram-negative strains and in-vitro antifungal against six different fungal strains. Compounds 6 g, 7 b, 7f, and 7 g exhibited significant activity against all bacterial strains ranging from MIC = 12.5-50 µg/mL, and compounds 6 g, 7 b, and 7 g exhibited considerable activity against all fungal strains ranging from MFC = 125-200 µg/mL. A molecular docking study indicated that compounds 6 g, 7 b, 7 g, and 7j could be lodged in the active pocket and inhibit C. albicans Sterol 14α-demethylase (CYP51) protein via various interactions, and these studies validate the antifungal results. Different parameters from the 100 ns MD simulation study are investigated to evaluate the dynamic stability of protein-ligand complexes. According to the MD simulation study, the proposed compounds effectively kept their molecular interaction and structural integrity within the C. albicans Sterol 14-demethylase. Compounds 6 g, 7 b, and 7 g are promising lead compounds in searching for novel antifungal drug-like molecules. Furthermore, in silico ADME indicates that these compounds possess drug-like physicochemical properties to be orally bioavailable.Communicated by Ramaswamy H. Sarma.

Design, synthesis, molecular docking, molecular dynamic simulation, and MMGBSA analysis of 7-O-substituted 5-hydroxy flavone derivatives.

A series of chrysin derivatives were designed, synthesized, and evaluated for their antibacterial activity against four different bacterial strains. We have synthesized new propyl-substituted and butyl-substituted chrysin-piperazine derivatives, which show marvellous inhibition against E. coli and S. aureus. The free hydroxyl group at the C-5 position of chrysin improved therapeutic efficacy in vivo and was a beneficial formulation for chemotherapy. All synthesized compounds were confirmed by various spectroscopic techniques such as IR, NMR, HPLC, and mass spectrometry. The compounds exhibited moderate to good inhibition, and their structure-activity relationship (SAR) has also been illustrated. Among the synthesised compounds, compounds 4 and 10 were the most active against S. pyogenes and E. coli, with 12.5 g/mL MICs; additionally, compound 12 exhibits significant activity on both the S. aureus and E. coli stains. Based on the promising activity profile and docking score of compound 12, it was selected for 100 ns MD simulation and post-dynamic binding free energy analysis within the active sites of S. aureus TyrRS (PDB ID: 1JIJ) and E. coli DNA GyrB (PDB ID: 6YD9) to investigate the stability of molecular contacts and to establish how the newly synthesized inhibitors fit together in the most stable conformations.Communicated by Ramaswamy H. Sarma.

4-nitroquinoline 1-oxide induces immune cells death to onset early immunosuppression during oral squamous cell carcinoma development.

4-Nitroquinoline N-oxide (4-NQO) and its derivatives react with genomic DNA to form stable quinolone monoadducts, which are highly mutagenic and genotoxic. While the chronic high-dose exposure of epithelial cells to a carcinogen such as 4-NQO leads to tumor development, its effect on other cells has not been explored yet. Since the immunosuppression due to aberrant immunological profile is recognized as a significant cause in tumors, here we determine the interaction between 4-NQO and immune cells both in vivo and in vitro, and its effect on oral squamous cell carcinoma (OSCC) progression in a murine model. Immune cell profiling of the spleen and peripheral blood revealed a significant decrease in the B-cell population in 4-NQO-exposed mice than the untreated group. Additionally, γδ T and CD5+ B lymphocyte populations decreased at both pre- and post-cancerous stages of OSCC. These results suggested that 4-NQO induced tumor transition from pre-malignant lesions to OSCC by altering certain immune cells systemically. Next, to establish the effect of 4-NQO on immune cells, human B- and T-cell lines were subjected to 4-NQO; the reduction in cell viability, increase in DNA damage response marker, and induction of apoptosis were more pronounced in B than T cells. Altogether, our results indicated that in addition to the genotoxicity of oral epithelial cells, 4-NQO potentiates long-range effects on specific immune cells to induce cell death to cause very-early immunosuppressive response during oral carcinogenesis, and thus immunosuppression and tumor development are coevolved.

A new class of 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl (piperidinyl)-1,3,5-triazine analogues with antimicrobial/antimycobacterial activity.

This study presents the synthesis and in vitro pharmacological evaluations of novel 2-(4-cyanophenyl amino)-4-(6-bromo-4-quinolinyloxy)-6-piperazinyl (piperidinyl)-1,3,5-triazines. The title compounds were assayed for their in vitro antimicrobial activity against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneria) and four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus clavatus, Candida albicans) using paper disc diffusion and agar streak dilution method as well as against Mycobacterium tuberculosis H37Rv strain using BACTEC MGIT and Lowenstein-Jensen MIC method. The bioassay results indicate that nine compounds namely 5d, 5h, 5n, 5p, 5q, 5r, 5s, 5t and 5u could be considered as possible potential agents with dual antimicrobial and antimycobacterial activities. The structures of the compounds were elucidated with the aid of IR, (1)H NMR, (13)C NMR, (19)F NMR spectroscopy and CHN analysis.

Synthesis of s-triazine-based thiazolidinones as antimicrobial agents.

A novel series of thiazolidinone derivatives, namely 4-{4-dimethylamino-6-[4-oxo-2-phenyl-5-(4-pyridin-2-yl-piperazin-1-ylmethyl)-thiazolidin-3-yl]-[1,3,5]-triazin-2-yloxy}-1-methyl-1H-quinolin-2-ones, have been synthesized from the key intermediate 4-(4-amino-6-dimethylamino-[1,3,5]-triazin-2-yloxy)-1-methyl-1H-quinolin-2-one (5). Compound 5 was condensed with various aldehydes to give Schiff base derivatives, which after cyclization gave thiazolidinones that were linked with 1-pyridin-2-yl-piperazine to obtain the target compounds. The newly synthesized compounds were evaluated for their antimicrobial activity against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, Shigella flexneri) and four fungi (Aspergillus niger, Candida albicans, Aspergillus fumigatus, Aspergillus clavatus).

Microwave-assisted synthesis of coumarin based 1,3,5-triazinyl piperazines and piperidines and their antimicrobial activities.

A series of 1,3,5-triazine derivatives that contain aniline, 4-hydroxycoumarin and 7-hydroxy-4-methylcoumarin and different piperazines and piperidines as substituents on the carbon atoms of the triazine ring has been synthesized by a simple and efficient synthetic protocol. Comparative studies were performed on above compounds, which were synthesized with conventional and microwave heating method. The microwave method was observed to be more beneficial as it provides an increase of yield and 90-95% reduction time. The antimicrobial activity of the compounds was tested against four bacteria (Staphylococcus aureus MTCC 96, B. subtilis MTCC 441, Escherichia coli MTCC 739, Pseudomonas aeruginosa MTCC 741) and two fungi (Aspergillus niger MTCC 282, Candida albicans MTCC 183). The preliminary in vitro evaluation studies revealed that some of the compounds have promising antimicrobial activities.

Microwave assisted synthesis and determination of in-vitro antimicrobial efficacy of well characterized s-triazinyl piperazines and piperidines.

An easy and convenient microwave-assisted synthesis of a library of s-triazinyl piperazines and piperidines, which, in addition to 4-aminobenzonitrile contain 8-hydroxyquinoline is described. The newly synthesized analogues were then subjected to determine their efficacy against some human pathogenic bacterial and fungal strains as 3 Gram negative bacteria (K. pneumoniae, S. typhi, P. vulgaris), 1 Gram positive bacteria (B. cereus) and 2 fungal species (A. clavatus, A. fumigatus) with an intent to develop novel class of antimicrobial agents. Microwave irradiation method was adopted for the final nucleophilic reactions, facilitates the condensation of piperazine and piperidine substituents to the s-triazine core. The results of bioassay showed that some of the newly synthesized s-triazines emerged as lead molecules with excellent MIC (mg/mL) values against the full array of bacterial and fungal pathogens comparable to the commercial antibiotics. The structure of final scaffolds has been affirmed on the basis of IR, 1H NMR, 13C NMR, 19F NMR and elemental analyses.

Commensal Fungus Candida albicans Maintains a Long-Term Mutualistic Relationship with the Host To Modulate Gut Microbiota and Metabolism.

Candida albicans survives as a commensal fungus in the gastrointestinal tract, and that its excessive growth causes infections in immunosuppressed individuals is widely accepted. However, any mutualistic relationship that may exist between C. albicans and the host remains undetermined. Here, we showed that a long-term feeding of C. albicans does not cause any noticeable infections in the mouse model. Our 16S and 18S ribosomal DNA (rDNA) sequence analyses suggested that C. albicans colonizes in the gut and modulates microbiome dynamics, which in turn mitigates high-fat-diet-induced uncontrolled body weight gain and metabolic hormonal imbalances. Interestingly, adding C. albicans to a nonobesogenic diet stimulated the appetite-regulated hormones and helped the mice maintain a healthy body weight. In concert, our results suggest a mutualism between C. albicans and the host, contrary to the notion that C. albicans is always an adversary and indicating it can instead be a bona fide admirable companion of the host. Finally, we discuss its potential translational implication as a probiotic, especially in obese people or people dependent on high-fat calorie intakes to manage obesity associated complications. IMPORTANCE Candida albicans is mostly considered an opportunistic pathogen that causes fetal systemic infections. However, this study demonstrates that in its commensal state, it maintains a long-term mutualistic relationship with the host and regulates microbial dynamics in the gut and host physiology. Thus, we concluded that C. albicans is not always an adversary but rather can be a bona fide admirable companion of the host. More importantly, as several genomic knockout strains of C. albicans were shown to be avirulent, such candidate strains may be explored further as preferable probiotic isolates to control obesity.

Vaccines against candidiasis: Status, challenges and emerging opportunity.

Candidiasis is a mycosis caused by opportunistic Candida species. The occurrence of fungal infections has considerably increased in the last few years primarily due to an increase in the number of immune-suppressed individuals. Alarming bloodstream infections due to Candida sp. are associated with a higher rate of morbidity and mortality, and are emerged as major healthcare concerns worldwide. Currently, chemotherapy is the sole available option for combating fungal diseases. Moreover, the emergence of resistance to these limited available anti-fungal drugs has further accentuated the concern and highlighted the need for early detection of fungal infections, identification of novel antifungal drug targets, and development of effective therapeutics and prophylactics. Thus, there is an increasing interest in developing safe and potent immune-based therapeutics to tackle fungal diseases. In this context, vaccine design and its development have a priority. Nonetheless, despite significant advances in immune and vaccine biology over time, a viable commercialized vaccine remains awaited against fungal infections. In this minireview, we enumerate various concerted efforts made till date towards the development of anti-Candida vaccines, an option with pan-fugal vaccine, vaccines in the clinical trial, challenges, and future opportunities.