Browsing by Author "Bari, Vinay Kumar"

Now showing 1 - 8 of 8

Azole resistance in Candida auris: mechanisms and combinatorial therapy
(John Wiley and Sons Inc, 2023-06-20T00:00:00) Jangir, Puneet; Kalra, Sapna; Tanwar, Sunita; Bari, Vinay Kumar
Multidrug resistance Candida auris is a dangerous fungal pathogen that is emerging at an alarming rate and posing serious threats to public health. C. auris is associated with nosocomial infections that cause invasive candidiasis in immunocompromised patients. Several antifungal drugs with distinct mechanisms of action are clinically approved for the treatment of fungal infections. The high rates of intrinsic and acquired drug resistance, particularly to azoles, reported in characterized clinical isolates of C. auris make treatment extremely problematic. In systemic infections, azoles are the first-line treatment for most Candida species; however, the increasing use of drugs results in the frequent emergence of drug resistance. More than 90% of the clinical isolates of C. auris is shown to be highly resistant to azole drugs especially fluconazole, with some strains (types) resistant to all three classes of commonly used antifungals. This presents a huge challenge for researchers in terms of completely understanding the molecular mechanism of azole resistance to develop more efficient drugs. Due to the scarcity of C. auris therapeutic alternatives, the development of successful drug combinations provides an alternative for clinical therapy. Taking advantage of various action mechanisms, such drugs in combination with azole are likely to have synergistic effects, improving treatment efficacy and overcoming C. auris azole drug resistance. In this review, we outline the current state of understanding about the mechanisms of azole resistance mainly fluconazole, and the current advancement in therapeutic approaches such as drug combinations toward C. auris infections. � 2023 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.
CRISPR/Cas9 mediated mutagenesis of MORE AXILLARY GROWTH 1 in tomato confers�resistance to root�parasitic weed Phelipanche aegyptiaca
(Nature Research, 2021-02-17T00:00:00) Bari, Vinay Kumar; Nassar, Jackline Abu; Aly, Radi
Root parasitic weeds infect numerous economically important crops, affecting total yield quantity and quality. A lack of an efficient control method limits our ability to manage newly developing and more virulent races of root parasitic weeds. To control the parasite induced damage in most host crops, an innovative biotechnological approach is urgently required. Strigolactones (SLs) are plant hormones derived from carotenoids via a pathway involving the Carotenoid Cleavage Dioxygenase (CCD) 7, CCD8 and More Axillary Growth 1 (MAX1) genes. SLs act as branching inhibitory hormones and strictly required for the germination of root parasitic weeds. Here, we demonstrate that CRISPR/Cas9-mediated�targted editing of SL biosynthetic gene MAX1, in�tomato confers�resistance against root parasitic weed Phelipanche aegyptiaca. We designed sgRNA to target the third exon of MAX1 in tomato plants using the CRISPR/Cas9 system. The T0 plants were edited very efficiently at the MAX1 target site without any non-specific off-target effects. Genotype analysis of T1 plants revealed that the introduced mutations were stably passed on to the next generation. Notably, MAX1-Cas9 heterozygous and homozygous T1 plants had similar morphological changes that include excessive growth of axillary bud, reduced plant height and adventitious root formation relative to wild type. Our results demonstrated that, MAX1-Cas9 mutant lines exhibit resistance against root parasitic weed P. aegyptiaca due to reduced SL (orobanchol) level. Moreover, the expression of carotenoid biosynthetic pathway gene PDS1 and total carotenoid level was altered, as compared to wild type plants. Taking into consideration, the impact of root parasitic weeds on the agricultural economy and the obstacle to prevent and eradicate them, the current study provides new aspects into the development of an efficient control method that could be used to avoid germination of root parasitic weeds. � 2021, The Author(s).
A critical role of farnesol in the modulation of Amphotericin B and Aureobasidin A antifungal drug susceptibility
(Taylor and Francis Ltd., 2022-10-29T00:00:00) Mahendrarajan, Venkatramanan; Bari, Vinay Kumar
Candida albicans and its related species can cause opportunistic infections such as �candidiasis� in immunocompromised individuals with a high morbidity and mortality rate. Several antifungal drugs available in the market are often used to treat infections caused by pathogenic fungi. However, in fungi, the development of resistance against these drugs quickly evolved. Candida is a dimorphic fungus that can switch between yeast to hyphae form, requires an active biosynthesis of membrane constituents. Sphingolipid and ergosterol molecules, are the major fungal plasma membrane components, and their interaction with the antifungal drug can modulate drug susceptibility. A lipophilic compound farnesol acts as a quorum-sensing molecule synthesised by the isoprenoid biosynthesis pathway in the fungal pathogen Candida. Farnesol is secreted in a cell density-dependent manner inhibits hyphae germination and biofilm formation. In this study, we have investigated whether the farnesol molecules affect the drug susceptibility of the antifungal drug Amphotericin B (AmB) which mainly binds with ergosterol, and Aureobasidin A (AbA), a complex sphingolipid biosynthesis inhibitor. Our studies revealed that a non-toxic and low concentration of farnesol can reduce the efficacy of AmB and AbA on yeast cells. This reduction is probably through the alteration in the complex sphingolipid biosynthesis and ATP-binding cassette (ABC) type membrane transport activity. These findings may shed light on a new direction to explore the role of lipid molecules in the antifungal drug resistance mechanisms in pathogenic yeast. � 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Emerging Role of Sphingolipids in Amphotericin B Drug Resistance
(Mary Ann Liebert Inc., 2023-06-16T00:00:00) Madaan, Kashish; Bari, Vinay Kumar
Invasive fungal infections in humans are common in people with compromised immune systems and are difficult to treat, resulting in high mortality. Amphotericin B (AmB) is one of the main antifungal drugs available to treat these infections. AmB binds with plasma membrane ergosterol, causing leakage of cellular ions and promoting cell death. The increasing use of available antifungal drugs to combat pathogenic fungal infections has led to the development of drug resistance. AmB resistance is not very common and is usually caused by changes in the amount or type of ergosterol or changes in the cell wall. Intrinsic AmB resistance occurs in the absence of AmB exposure, whereas acquired AmB resistance can develop during treatment. However, clinical resistance arises due to treatment failure with AmB and depends on multiple factors such as the pharmacokinetics of AmB, infectious fungal species, and host immune status. Candida albicans is a common opportunistic pathogen that can cause superficial infections of the skin and mucosal surfaces, thrush, to life-Threatening systemic or invasive infections. In addition, immunocompromised individuals are more susceptible to systemic infections caused by Candida, Aspergillus, and Cryptococcus. Several antifungal drugs with different modes of action are used to treat systemic to invasive fungal infections and are approved for clinical use in the treatment of fungal diseases. However, C. albicans can develop a variety of defenses against antifungal medications. In fungi, plasma membrane sphingolipid molecules could interact with ergosterol, which can lead to the alteration of drug susceptibilities such as AmB. In this review, we mainly summarize the role of sphingolipid molecules and their regulators in AmB resistance. � Copyright 2023, Mary Ann Liebert, Inc., publishers 2023.
A genome editing approach to enhance host resistance against plant-parasitic weeds
(Nova Science Publishers, Inc., 2023-08-14T00:00:00) Bari, Vinay Kumar
Root-specific plant-parasitic weeds Phelipanche and Orobanche spp. (broomrape) induce potential damage to numerous crops and lead to heavy loss to the economy due to a reduction in total yield, especially in the Mediterranean, Europe, Africa and Asian countries. The lack of effective control measures restricts our capabilities to avoid newly developing and more virulent races of parasitic weeds, hence, innovative solutions are urgently needed to control these parasites. Significant research towards deciphering the plant genome and its functions have been made over the years, including the genome of the root parasitic weed Phelipanche aegyptiaca. Recent biotechnological advancements in genome manipulation such as silencing RNA molecules and T-DNA insertions have been significantly used for introducing resistance against several parasitic weeds. However, the available strategies to generate host resistance to the plant-parasitic weed need further advancement. Several different methods for the control of parasitic weeds (such as herbicide, and breeding resistant variety crops) have been adopted in attempts to reduce germination of Orobanche commonly known as broomrapes, but several difficulties arise in targeting specific plant-plants (host plant and parasitic plant) interaction systems. Moreover, most control strategies to manage parasitic weeds have considerable drawbacks and are less effective. Recently developed gene-editing technology CRISPR/Cas9 has been used in numerous crops to enhance desired plant phenotypes and the same technique can also be employed to target the essential key processes of host-parasite interactions, such as strigolactone (SL) biosynthesis, signalling, haustorium development, and penetration of the host cell wall. A major attempt has been made to edit host genes rather than parasite- specific genes using CRISPR/Cas9 since the germination of these parasites is itself induced by the host. In this chapter, we summarize and discuss the genome editing approach used to edit the host-specific genes which confer resistance to root-specific plant-parasitic weeds. � 2023 by Nova Science Publishers, Inc. All rights reserved.
Silencing of a mannitol transport gene in Phelipanche aegyptiaca by the tobacco rattle virus system reduces the parasite germination on the host root
(Taylor and Francis Ltd., 2022-11-24T00:00:00) Bari, Vinay Kumar; Singh, Dharmendra; Nassar, Jackline Abu; Aly, Radi
Root parasitic weed Phelipanche aegyptiaca is an obligate plant parasite that causes severe damage to host crops. Agriculture crops mainly belong to the Brassicaceae, Leguminosae, Cruciferae, and Solanaceae plant families affected by this parasitic weed, leading to the devastating loss of crop yield and economic growth. This root-specific parasitic plant is not able to complete its life cycle without a suitable host and is dependent on the host plant for nutrient uptake and germination. Therefore, selected parasitic genes of P. aegyptiaca which were known to be upregulated upon interaction with the host were chosen. These genes are essential for parasitism, and reduced activity of these genes could affect host-parasitic interaction and provide resistance to the host against these parasitic weeds. To check and examine the role of these parasitic genes which can affect the development of host resistance, we silenced selected genes in the P. aegyptiaca using the tobacco rattle virus (TRV) based virus-induced gene silencing (VIGS) method. Our results demonstrated that the total number of P. aegyptiaca parasite tubercles attached to the root of the host plant Nicotiana benthamiana was substantially decreased in all the silenced plants. However, silencing of the P. aegyptiaca MNT1 gene which encodes the mannitol transporter showed a significantly reduced number of germinated shoots and tubercles. Thus, our study indicates that the mannitol transport gene of P. aegyptiaca plays a crucial role in parasitic germination, and silencing of the PaMNT1 gene abolishes the germination of parasites on the host roots. � 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.
Targeted mutagenesis of two homologous ATP-binding cassette subfamily G (ABCG) genes in tomato confers resistance to parasitic weed Phelipanche aegyptiaca
(Springer Japan, 2021-03-11T00:00:00) Bari, Vinay Kumar; Nassar, Jackline Abu; Meir, Ayala; Aly, Radi
Phelipanche aegyptiaca and Orobanche spp. are obligate plant root-parasitic weeds that cause extensive damage in agricultural crop plants. Their germination requires exposure to strigolactones (SLs) exuded by the host plant roots. Here we studied genes in the host plant tomato involved in SL exudation and their impact on parasitic weeds. We provide evidence that CRISPR/Cas9-mediated targeted mutagenesis of two homologous ATP-binding cassette subfamily G (ABCG) genes, ABCG44 (Solyc08g067610) and ABCG45 (Solyc08g067620), in tomato significantly reduces SLs in the root exudate and abolishes germination of the root-parasitic weed P. aegyptiaca. Based on genome sequence similarity between ABCG44 and ABCG45, a 20-bp target sequence in their exon region was selected to design single guide RNA targeting both genes using CRISPR/Cas9. The plant binary vector constructs harboring the specific Cas9 and single guide RNA were transformed into tomato. Selected T0 mutated tomato plants showed different types of deletions at both gene loci. Genotype analysis of T1 plants suggested stable inheritance of the introduced mutations without any potential off-target effects. The phenotype of Cas9-mutated plants included increased shoot branching and growth of axillary buds, and reduced length of primary stems. Interestingly, reduced germination of P. aegyptiaca resulted from a decrease in the SL orobanchol in the root exudate of Cas9-mutated plants; however, orobanchol content in the root extract was unchanged compared to control plants. Moreover, in single and double ABCG mutants, expression of the SL-biosynthesis genes CCD8 and MAX1 decreased. The current study offers insights into CRISPR-mediated mutagenesis of ABCG genes, which could serve as an efficient control method to prevent root-parasitic weed germination. � 2021, The Botanical Society of Japan.
Using biotechnological approaches to develop crop resistance to root parasitic weeds
(Springer Science and Business Media Deutschland GmbH, 2021-04-12T00:00:00) Aly, Radi; Matzrafi, Maor; Bari, Vinay Kumar
Main conclusion: New transgenic and biotechnological approaches may serve as a key component in achieving crop resistance to root parasitic weeds. Abstract: Root parasitic weeds inflict severe damage to numerous crops, reducing yield quantity and quality. A lack of new sources of resistance limits our ability to manage newly developing, more virulent races. Having no effective means to control the parasites in most crops, innovative biotechnological solutions are needed. Several novel biotechnological strategies using regulatory RNA molecules, the CRISPR/Cas9 system, and T-DNA insertions have been acknowledged for engineering resistance against parasitic weeds. Significant breakthroughs have been made over the years in deciphering the plant genome and its functions, including the genomes of parasitic weeds. However, the basis of biotechnological strategies to generate host resistance to root parasitic weeds needs to be further developed. Gene-silencing and editing tools should be used to target key processes of host�parasite interactions, such as strigolactone biosynthesis and signaling, haustorium development, and degradation and penetration of the host cell wall. In this review, we summarize and discuss the main areas of research leading to the discovery and functional analysis of genes involved in host-induced gene silencing that target key parasite genes, transgenic host modification, and host gene editing to generate sustainable resistance to root parasitic weeds. � 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.