M. Owais

Virulence and Pathogenicity of Fungal Pathogens with Special Reference to Candida albicans

The frequency of severe systemic fungal diseases has increased in the last few decades. The clinical use of broad spectrum antibacterial drugs and immunosuppressive agents after organ transplantation, cancer chemotherapy, and advancements in surgery are associated with increasing risk of fungal infection. Despite the effectiveness of available antifungals in combating such infections, the emergence of drug resistance to antifungals, and problems of toxicity and poor delivery of drugs at the target site in systemic infections, have necessitated a systematic approach to the study of fungal pathogens, host–fungi interactions, and identification of virulence factors. Characterization of virulence factors is expected to improve understanding of fungal pathogenesis and to help explore new drug targets. In this article we discuss the process of fungal infections, virulence factors and pathogenicity of fungal pathogens, with special reference to Candida albicans. Adherence, dimorphism, phenotypic switching, secretion of hydrolytic enzymes, biofilm formation, and ability to adapt at host body temperature are some of the well-known virulence factors among pathogenic fungi and are discussed in relation to C. albicans.

Use of Tuftsin Bearing Nystatin Liposomes against an Isolate of Candida albicans showing Less In Vivo Susceptibility to Amphotericin B

In the present study, we evaluated tuftsin bearing nystatin liposomes for their potential against an isolate of Candida albicans (C. albicans) showing less in vivo susceptibility to amphotericin B (Amp B). The liposomised-Amp B in higher doses was found to be effective in elimination of less susceptible strain of C. albicans (C. albicans JMCR) in Balb/c mice, but may not be recommended due to toxicity constraints. On the other hand, liposomal nystatin was shown to possess higher efficacy as compared to that of Amp B, and was pertinent in treatment of C. albicans JMCR strain. The data of present work reveals that the incorporation of nystatin in tuftsin-bearing-liposomes results in a significant increase in its efficacy against experimental murine candidiasis. Interestingly, the pre-treatment of animals with liposomised-tuftsin prior to challenge with C. albicans infection was more effective in elimination of the pathogen from host and shows an advantage in prophylactic perspectives.

Antifungal Activity of Medicinal Plant Extracts and Phytocompounds: A Review

The epidemiological data suggest that the incidence and prevalence of serious mycoses continues to be a public health problem. The increased use of antifungal agents has resulted in the development of resistance to these drugs. The spread of multidrug-resistant strains of fungus and the reduced number of drugs available make it necessary to discover new classes of antifungals from natural products including medicinal plants. Historically, herbs and spices have enjoyed a rich tradition of use for their medicinal properties and provide unlimited opportunities for new drug leads because of the huge chemical diversity. Assays of bioactive compounds have been reported with good antifungal properties in vitro or in vivo. It is almost impossible to discuss the various characteristics of these plants such as mode of action and extraction of active compounds in a single review. Therefore, we have focussed here mainly on the antifungal plant extracts, their use against pathogeinc and drug resistant fungi. The various classes of compounds such as phenolics, terpenoids, saponins, and alkaloids, etc., are discussed in detail. The new emerging classes of antifungal proteins and peptides are also reviewed briefly. In this chapter, we also describe the technical aspects related to the methodology for screening and identification of antifungal compounds. The technical aspects regarding the use of reliable methodology of extraction, screening, bioautography, and identification of pure compounds from crude extracts and fractions are also discussed here.

Resol based chitosan/nano-hydroxyapatite nanoensemble for effective bone tissue engineering

It is the first report where different amounts of resol resin (RS) were incorporated with chitosan-hydroxyapatite (CHA) to develop a triconstituent nanoensemble CHA-RS(0.5,1,2), via simple co-precipitation method. The results of SEM, TEM, TGA and mechanical analysis revealed irregular interconnected rough morphology with homogenous distribution of needle shaped particles having average size ranging between 12 and 19nm, possessing higher thermal stability and mechanical strength, respectively relative to CHA (binary) nanocomposite. The CHA-1RS nanocomposite showed enhanced protein adsorption and ALP activity with excellent apatite formation ability compared to CHA-RS(0.5,2) and CHA nanocomposites. Thus, CHA-1RS nanocomposite was selectively tested as bare implant in the repair of critical-size calvarium defect (8mm) in albino rat. The histopathological and radiological investigations indicated that CHA-1RS prompted the bone regeneration ability as early as 2 weeks postimplantation demonstrating remarkably faster healing of calvarial defect relative to Cerabone. These findings have placed CHA-1RS on the pedestal to be employed as a potential alternative biomaterial for bone tissue engineering.

Combinational Antifungal Therapy and Recent Trends in Drug Discovery

Invasive fungal infections are a major problem in immunocompromised patients. This has necessitated an increased interest in the development of new antifungals to treat these life-threatening infections. However, our means of combating fungal infections are still lagging behind those for bacterial infections, due to toxicity and the lower clinical efficacy of available antifungals against some invasive fungal infection. Thus, more efforts are needed in antifungal drug discovery, as well as in developing effective ways of minimizing toxicity and improving delivery of available antifungal drugs. One approach is the effective use of newer antifungal agents in combination therapy against invasive aspergillosis, cryptococcosis and candidiasis. On the other hand, identifying and validating new antifungal drug targets is a prerequisite for new antifungal drug discovery. These new targets might be discovered by both conventional but improved assays and genomic approaches. Also, targeting virulence is expected to be a new paradigm for antifungals. In this chapter, an attempt is made to describe recent progress in combinational therapy and new approaches to antifungal drug discovery.

Synergistic combination of natural bioadhesive bael fruit gum and chitosan/nano-hydroxyapatite: A ternary bioactive nanohybrid for bone tissue engineering

In this work, we have explored the polysaccharide nature of bael fruit gum (BFG) motivated from the current findings about the substantial role of the polysaccharides in bone tissue engineering. The nanocomposite scaffold (CSH-BFG) was prepared by blending BFG, nano-hydroxyapatite (n-HA) and chitosan (CS) by co-precipitation approach and compared with n-HA and CS binary system (CSH). The analysis of different properties was carried out by SEM, TEM, FTIR, XRD and mechanical testing. The CSH-BFG scaffolds revealed a rough morphology and uniform distribution of particles along with strong chemical interactions among different components compared to the CSH scaffold. The incorporation of BFG in the scaffold resulted in significant increase of the compressive strength, compressive modulus, protein adsorption, biodegradation and swelling behaviour. The ternary system exhibited superior antibacterial activity against different bacterial pathogens compared to the binary system. The in vitro biomineralization ability was elucidated from the formation of thick apatite layer complementing the result of ARS study in the CSH-BFG nanocomposite. Our findings also revealed that BFG reinforced CSH nanocomposite exhibited enhanced cell adhesion and proliferation, osteogenic differentiation along with phenomenal cytocompatibility. Overall, our results signified that the fabricated CSH-BFG nanocomposite carries enormous potential to be applied in the bone remodelling procedures.