Peer Abdul Haseeb Shah, Ph. D.
DST INSPIRE Faculty
Department of Bioresources
University of Kashmir, Srinagar-J&K 190006, India.
Drug resistance is a common phenomenon seen during the treatment of life-threatening diseases like cancer, tuberculosis etc making cells resistant to the variety of different drugs called multidrug resistance (MDR). There have been reports of drug resistance from all the life forms ranging from microbial pathogens to human cells. Resistance to antifungal drugs varies to the different extent with the type of drug in use and also among different fungi, either due to differences in the composition of the cell membrane and cell wall components or due to the difference in the ability to generate the drug-resistant variants. Due to the frequent use of drugs, MDR phenomenon is also observed in a large number of pathogenic fungal species. Although many antifungal drugs are being used commonly to tackle the menace of fungal infections due to development of drug resistance these drugs have become less effective. One important shortfall to the development of new varieties of antifungal drugs is that it is difficult to delineate the unique pathway in fungi against which drugs can be developed and in some cases, the drugs show toxicity to human hosts as well. One of the aims of our laboratory is to look for novel molecules/compounds (either synthetic or natural), which can be effective against pathogenic human fungi and can be looked as potential antifungal molecules.
Overexpression of drug efflux pumps has been one of the major factors responsible for the development of antifungal drug resistance. Many of the membrane drug transporters of yeast particularly in highly pathogenic Candida albicans have been under study in recent years. Although many groups are working on the role of drug efflux transporters at the level of their expression and transcriptional regulation there are many unmet aspects to analyze the role-played by transporters in multidrug resistance. Many aspects related to post-translational modifications of membrane proteins having the role in the development of drug resistance have not been studied. Although not much worked upon, still there are few studies highlighting the importance of post-translational modifications in the maturation and localization of membrane transporter proteins. Our group is currently focusing on the study of these PTMs of membrane proteins of yeast having role in fungal drug resistance and pathogencity.
Current Research Grants:
S. No/ No.
Drug resistance in fungi and the …. PTM of membrane proteins (Ongoing)
Department of Science and Technology (DST-INDIA)
Clinical drug resistant strains of …. drug resistance and drug tolerance (Ongoing)
Science & Engineering Research Board (SERB-INDIA)
Asiya Ramzan (Ph. D. Student)
Sajad Ahmad Padder (Ph. D. Student/Project JRF)
Hafsa Qadri (Project Fellow)
• W1038 near D-loop of NBD2 is a focal point for inter-domain communication in multidrug transporter Cdr1 of Candida albicans. Banerjee A, Shah AH, Redhu AK, Moreno A, Falson P, Prasad R*. Biochim Biophys Acta. 2018;1860(5):965-972.
• Molecular Basis of Substrate Polyspecificity of the Candida albicans Mdr1p Multidrug/H+ Antiporter. Redhu AK, Banerjee A, Shah AH, Moreno A, Rawal MK, Nair R, Falson P, Prasad R*. J Mol Biol. 2018;430(5):682-694.
• Newly identified motifs in Candida albicans Cdr1 protein nucleotide binding domains are pleiotropic drug resistance subfamily-specific and functionally asymmetric. Rawal MK, Banerjee A, Shah AH, Khan MF, Sen S, Saxena AK, Monk BC, Cannon RD, Bhatnagar R, et al., Prasad R*. Sci Rep. 2016;6:27132.
• ABC transporter Cdr1p harbors charged residues in the intracellular loop and nucleotide-binding domain critical for protein trafficking and drug resistance. Shah AH, Banerjee A, Rawal MK, Saxena AK, Mondal AK, Prasad R*. FEMS Yeast Res. 2015;15(5):fov036.
• Mutational Analysis of Intracellular Loops Identify Cross Talk with Nucleotide Binding Domains of Yeast ABC Transporter Cdr1p. Shah AH, Rawal MK, Dhamgaye S, Komath SS, Saxena AK, Prasad R*. Sci Rep. 2015;5:11211.
• Novel role of a family of major facilitator transporters in biofilm development and virulence of Candida albicans. Shah AH, Singh A, Dhamgaye S, Chauhan N, Vandeputte P, Suneetha KJ, Kaur R, Mukherjee PK, Chandra J, Ghannoum MA, et. al Prasad R*. Biochem J . 2014;460(2):223-35.
• In vitro effect of malachite green on Candida albicans involves multiple pathways and transcriptional regulators UPC2 and STP2. Dhamgaye S, Devaux F, Manoharlal R, Vandeputte P, Shah AH, Singh A, Blugeon C, Sanglard D, Prasad R*. Antimicrob Agents Chemother. 2012;56(1):495-506.
• Alanine scanning of all cysteines and construction of a functional cysteine-less Cdr1p, a multidrug ABC transporter of Candida albicans. Prasad R*, Shah AH, Sanwal H, Kapoor K. Biochem Biophys Res Commun. 2012;417(1):508-13.
• Quorum sensing: A less known mode of communication among fungi. Padder SA, Prasad R, Shah AH*. Microbiol Res. 2018;210:51-58.
• Resistance to antifungal therapies. Prasad R*, Banerjee A, Shah AH. Essays Biochem. 2017;61(1):157-166.
• MFS transporters of Candida species and their role in clinical drug resistance. Redhu AK, Shah AH, Prasad R*. FEMS Yeast Res. 2016;16(4)pii: fow043.
• Antifungals: Mechanism of Action and Drug Resistance. Prasad R*, Shah AH, Rawal MK. Adv Exp Med Biol. 2016;892:327-349.
• Candida Efflux ATPases and Antiporters in Clinical Drug Resistance. Prasad R*, Rawal MK, Shah AH. Adv Exp Med Biol. 2016;892:351-376.
• Tools and Techniques to Study Multidrug Transporters of Yeasts. Shah AH, Shukla S, Prasad R *. In: Varma A., Sharma A. (eds) Modern Tools and Techniques to Understand Microbes. Springer, Cham 2017; 183-207.
• Mechanisms of drug resistance in fungi and their significance in biofilms. Prasad R*, Shah AH, Dhamgaye S. In: Rumbaugh K., Ahmad I. (eds) Antibiofilm Agents. Springer Series on Biofilms, vol 8. Springer, Berlin, Heidelberg 2014; 45-65.