M. Anaul Kabir

Bio: M. Anaul Kabir is an academic researcher from National Institute of Technology Calicut. The author has contributed to research in topics: Candida albicans & Chaperonin. The author has an hindex of 12, co-authored 20 publications receiving 477 citations. Previous affiliations of M. Anaul Kabir include University of Rochester Medical Center & East Tennessee State University.

Candida albicans: A Model Organism for Studying Fungal Pathogens.

Abstract: Candida albicans is an opportunistic human fungal pathogen that causes candidiasis As healthcare has been improved worldwide, the number of immunocompromised patients has been increased to a greater extent and they are highly susceptible to various pathogenic microbes and C albicans has been prominent among the fungal pathogens The complete genome sequence of this pathogen is now available and has been extremely useful for the identification of repertoire of genes present in this pathogen The major challenge is now to assign the functions to these genes of which 13% are specific to C albicans Due to its close relationship with yeast Saccharomyces cerevisiae, an edge over other fungal pathogens because most of the technologies can be directly transferred to C albicans from S cerevisiae and it is amenable to mutation, gene disruption, and transformation The last two decades have witnessed enormous amount of research activities on this pathogen that leads to the understanding of host-parasite interaction, infections, and disease propagation Clearly, C albicans has emerged as a model organism for studying fungal pathogens along with other two fungi Aspergillus fumigatus and Cryptococcus neoformans Understanding its complete life style of C albicans will undoubtedly be useful for developing potential antifungal drugs and tackling Candida infections This will also shed light on the functioning of other fungal pathogens

Loss and gain of chromosome 5 controls growth of Candida albicans on sorbose due to dispersed redundant negative regulators

Abstract: A reversible decrease or increase of Candida albicans chromosome copy number was found to be a prevalent means of survival of this opportunistic pathogen, under conditions that kill cells or inhibit their propagation. The utilization of a secondary carbon source, l-sorbose, by reversible loss of chromosome 5, serves as a model system. We have determined that an ≈209-kbp portion of the right arm of chromosome 5 contains at least five spatially separated, functionally redundant regions that control utilization of l-sorbose. The regions bear no structural similarity among themselves, and four of them contain sequences that bear no similarity with any known sequence. We identified a regulatory gene in region A that encodes a helix-loop-helix protein. Most important, the multiple redundant regulators scattered along chromosome 5 explain, in a simple, elegant way, why the loss of the entire homologue is usually required for growth on sorbose. Thus, an entire chromosome acts as a single regulatory unit, a feature not previously considered. Our finding appears to be a paradigm for the control of other phenotypes in C. albicans that also depend on chromosome loss, thus implying that C. albicans genes are not distributed randomly among different chromosomes.

Candida Infections and Their Prevention

Abstract: Infections caused by Candida species have been increased dramatically worldwide due to the increase in immunocompromised patients. For the prevention and cure of candidiasis, several strategies have been adopted at clinical level. Candida infected patients are commonly treated with a variety of antifungal drugs such as fluconazole, amphotericin B, nystatin, and flucytosine. Moreover, early detection and speciation of the fungal agents will play a crucial role for administering appropriate drugs for antifungal therapy. Many modern technologies like MALDI-TOF-MS, real-time PCR, and DNA microarray are being applied for accurate and fast detection of the strains. However, during prolonged use of these drugs, many fungal pathogens become resistant and antifungal therapy suffers. In this regard, combination of two or more antifungal drugs is thought to be an alternative to counter the rising drug resistance. Also, many inhibitors of efflux pumps have been designed and tested in different models to effectively treat candidiasis. However, most of the synthetic drugs have side effects and biomedicines like antibodies and polysaccharide-peptide conjugates could be better alternatives and safe options to prevent and cure the diseases. Furthermore, availability of genome sequences of Candida albicans and other non-albicans strains has made it feasible to analyze the genes for their roles in adherence, penetration, and establishment of diseases. Understanding the biology of Candida species by applying different modern and advanced technology will definitely help us in preventing and curing the diseases caused by fungal pathogens.

Chromosome instability and unusual features of some widely used strains of Candida albicans

Abstract: Electrophoretic karyotyping of the Candida albicans revealed a different migration pattern of ChR in three different stocks of the sequencing strain SC5314. In one stock, the high instability of ChR size prevented the migration of ChR as a compact band; ChR appeared, instead, as a smear. In some stocks, ChR and/or Ch1 ploidy diminished, suggesting mixed populations of disomic and monosomic cells. Similarly, some stocks of widely used derivatives CAI4 and BWP17 contained smearing of ChR. In addition, the most manipulated strain in the lineage of SC5314, the last derivative, BWP17, acquired an increase in the size of Ch7b and revealed an unusual property. BWP17 did not tolerate a well-established procedure of telomere-mediated fragmentation of a chromosome; the remaining intact homologue always duplicated. We suggest that some stocks of SC5314 are unstable and that BWP17 may not be appropriate for general studies. Instead of BWP17 or CAI4, we recommend using for general research CAF4-2, which is a relatively stable Ura- derivative, and which has been successfully used for more than a decade in our laboratory.

Random-coil behavior and the dimensions of chemically unfolded proteins

Abstract: Spectroscopic studies have identified a number of proteins that appear to retain significant residual structure under even strongly denaturing conditions. Intrinsic viscosity, hydrodynamic radii, and small-angle x-ray scattering studies, in contrast, indicate that the dimensions of most chemically denatured proteins scale with polypeptide length by means of the power-law relationship expected for random-coil behavior. Here we further explore this discrepancy by expanding the length range of characterized denatured-state radii of gyration (RG) and by reexamining proteins that reportedly do not fit the expected dimensional scaling. We find that only 2 of 28 crosslink-free, prosthetic-group-free, chemically denatured polypeptides deviate significantly from a power-law relationship with polymer length. The RG of the remaining 26 polypeptides, which range from 16 to 549 residues, are well fitted (r2 = 0.988) by a power-law relationship with a best-fit exponent, 0.598 ± 0.028, coinciding closely with the 0.588 predicted for an excluded volume random coil. Therefore, it appears that the mean dimensions of the large majority of chemically denatured proteins are effectively indistinguishable from the mean dimensions of a random-coil ensemble.

Efflux-Mediated Antifungal Drug Resistance

Abstract: Fungi cause serious infections in the immunocompromised and debilitated, and the incidence of invasive mycoses has increased significantly over the last 3 decades. Slow diagnosis and the relatively few classes of antifungal drugs result in high attributable mortality for systemic fungal infections. Azole antifungals are commonly used for fungal infections, but azole resistance can be a problem for some patient groups. High-level, clinically significant azole resistance usually involves overexpression of plasma membrane efflux pumps belonging to the ATP-binding cassette (ABC) or the major facilitator superfamily class of transporters. The heterologous expression of efflux pumps in model systems, such Saccharomyces cerevisiae, has enabled the functional analysis of efflux pumps from a variety of fungi. Phylogenetic analysis of the ABC pleiotropic drug resistance family has provided a new view of the evolution of this important class of efflux pumps. There are several ways in which the clinical significance of efflux-mediated antifungal drug resistance can be mitigated. Alternative antifungal drugs, such as the echinocandins, that are not efflux pump substrates provide one option. Potential therapeutic approaches that could overcome azole resistance include targeting efflux pump transcriptional regulators and fungal stress response pathways, blockade of energy supply, and direct inhibition of efflux pumps.

Biology of the Heat Shock Response and Protein Chaperones: Budding Yeast (Saccharomyces cerevisiae) as a Model System

Abstract: Summary: The eukaryotic heat shock response is an ancient and highly conserved transcriptional program that results in the immediate synthesis of a battery of cytoprotective genes in the presence of thermal and other environmental stresses. Many of these genes encode molecular chaperones, powerful protein remodelers with the capacity to shield, fold, or unfold substrates in a context-dependent manner. The budding yeast Saccharomyces cerevisiae continues to be an invaluable model for driving the discovery of regulatory features of this fundamental stress response. In addition, budding yeast has been an outstanding model system to elucidate the cell biology of protein chaperones and their organization into functional networks. In this review, we evaluate our understanding of the multifaceted response to heat shock. In addition, the chaperone complement of the cytosol is compared to those of mitochondria and the endoplasmic reticulum, organelles with their own unique protein homeostasis milieus. Finally, we examine recent advances in the understanding of the roles of protein chaperones and the heat shock response in pathogenic fungi, which is being accelerated by the wealth of information gained for budding yeast.