• Title/Summary/Keyword: pathogen resistance

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Computational Identification of Essential Enzymes as Potential Drug Targets in Shigella flexneri Pathogenesis Using Metabolic Pathway Analysis and Epitope Mapping

  • Narad, Priyanka;Himanshu, Himanshu;Bansal, Hina
    • Journal of Microbiology and Biotechnology
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    • v.31 no.4
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    • pp.621-629
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    • 2021
  • Shigella flexneri is a facultative intracellular pathogen that causes bacillary dysentery in humans. Infection with S. flexneri can result in more than a million deaths yearly and most of the victims are children in developing countries. Therefore, identifying novel and unique drug targets against this pathogen is instrumental to overcome the problem of drug resistance to the antibiotics given to patients as the current therapy. In this study, a comparative analysis of the metabolic pathways of the host and pathogen was performed to identify this pathogen's essential enzymes for the survival and propose potential drug targets. First, we extracted the metabolic pathways of the host, Homo sapiens, and pathogen, S. flexneri, from the KEGG database. Next, we manually compared the pathways to categorize those that were exclusive to the pathogen. Further, all enzymes for the 26 unique pathways were extracted and submitted to the Geptop tool to identify essential enzymes for further screening in determining the feasibility of the therapeutic targets that were predicted and analyzed using PPI network analysis, subcellular localization, druggability testing, gene ontology and epitope mapping. Using these various criteria, we narrowed it down to prioritize 5 novel drug targets against S. flexneri and one vaccine drug targets against all strains of Shigella. Hence, we suggest the identified enzymes as the best putative drug targets for the effective treatment of S. flexneri.

Spatial Network Analysis of Pathogen Spread in Korean Rice Farming Areas Using Graph Theory (그래프 이론을 적용한 벼 병원균 확산 공간 연결망 분석)

  • Kang, Wanmo;Lee, Dowon;Park, Chan-Ryul
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.15 no.4
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    • pp.201-209
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    • 2013
  • The spread and expansion of pests and pathogens due to climate change have caused considerable reduction of rice yield in agricultural landscapes. This study was conducted to quantitatively analyze the spread of rice pathogens carried by insect pests on spatial network in South Korea using graph-theoretic methods. We identified the connectivity "backbone" of pathogen spread network among the cities along the coastal area of West Sea. In addition, we graphically represented 1) the core areas that can cause local and regional outbreaks of pathogens; and 2) the areas that act as bottlenecks in the spread of pathogen which can link the core areas. Especially, the cities in the coastal areas of West Sea that have the high density of rice crops, represented a low spread resistance to pathogen infection. These results may suggest insights into planning the integrated pest management possibly through regional collaboration.

Studies on the Function of Peroxidasins in Innate Immune System in C. elegans

  • Cho, Jeong Hoon
    • Journal of Integrative Natural Science
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    • v.12 no.4
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    • pp.142-146
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    • 2019
  • Peroxidasin is a unique member of peroxidase family in that it has extracellular matrix (ECM) motif as well as peroxidase activity. Peroxidasins are involved in consolidation the extracellular matrix during development and in innate immune defense. C. elegans has two functional peroxidasins, PXN-1 and PXN-2, and PXN-2 is known to contribute to innate immune system. However, it is not clear of PXN-1 function in innate immune system. Therefore, this study is focused on the function of PXN-1 and the relationship between PXN-1 and PXN-2 in innate defense system in C. elegans. When pxn-1 was knocked down by RNAi, the worm turned to be more resistant to pathogens, Staphylococcus aureus and Pseudomonas aeruginosa and the enhanced resistance was abolished in pxn-1pxn-2 double knock down. By contrast, pxn-2 knock down showed stronger susceptibility to the pathogens. These results suggest that pxn-2 can contribute the pathogen resistance and pxn-1 can suppress the pathogen resistance. To confirm the idea, overexpression experiments were performed. Overexpression of pxn-1 showed more susceptible to pathogens compared to the control and double overexpression of pxn-1pxn-2 overcame the susceptibility of pxn-1 overexpression to the pathogens. On the other hand, pxn-2 overexpression made the worm more resistant to the pathogens and the resistance was maintained in pxn-1pxn-2 double overexpression. The comparison of the susceptibilities to the bacterial pathogens in above mentioned constructs suggests that PXN-1 suppress the function of PXN-2 in defense against bacterial pathogens in Caenorhabditis elegans.

Screening Resistance to Crown Gall Disease by Pathogen Inoculation in Muscadine and Florida Hybrid Grapes (병원균 접종에 의한 Muscadine 및 플로리다 교잡종 포도의 줄기혹병 저항성 검정)

  • Noh, Jung-Ho;Park, Kyo-Sun;Lu, Jiang;Yun, Hae-Keun
    • Korean Journal of Organic Agriculture
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    • v.23 no.3
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    • pp.497-507
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    • 2015
  • It is necessary to evaluate the resistance to disease among genetic resources for development of disease resistant grapes. This study was conducted to screen the resistance to crown gall in muscadine and Florida hybrid bunch grapes by pathogen inoculation. In order to compare the responses to infection with different pathogen strains, muscadine and Florida hybrid grapes were inoculated with 3 strains of Agrobacterium vitis. Although there were different levels crown gall formation among grape cultivars, there little variation in response to inoculated strains. Among 29 muscadine cultivars tested by inoculation of A. vitis 'C4612', most of them were shown to be susceptible, and 'Gold Isle' and 'Africa Queen' were highly susceptible, and two cultivars, 'Welder' and 'Jumbo' were found to be resistant to crown gall disease. Among Florida hybrid grapes, 'Daytona', 'Stover', and 'Swanee' were susceptible and 'Blanc du Bois' was moderately susceptible to crown gall. Because muscadine grapes have been actively utilized as useful genetic resources for development of new grape varieties by intersub-genus cross, this result from the screening of resistance among muscadine grapes can provide valuable information in breeding programs of grape resistant to crown gall.

Different oxidative burst patterns occur during host and nonhost resistance responses triggered by Xanthomonas campestris in pepper

  • Kwak, Youn-Sig;Han, Ki-Soo;Lee, Jung-Han;Lee, Kyung-Hee;Chung, Woo-Sik;Mysore, Kirankumar S.;Kwon, Young-Sang;Kim, Hee-Kyu;Bae, Dong-Won
    • Journal of Plant Biotechnology
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    • v.36 no.3
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    • pp.244-254
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    • 2009
  • The hypersensitive reaction (HR) is the most common plant defense reaction against pathogens. HR is produced during both host- and nonhost-incompatible interactions. Several reports suggest that similarities exist between host and nonhost resistances. We assayed the pattern of generation of reactive oxygen species (ROS) and scavenging enzyme activities during nonhost pathogen-plant interactions (Xanthomonas campestris pv. campestris/Capsicum annuum L.) and incompatible host pathogen-plant interactions (Xanthomonas campestris pv. vesicatoria race1/Capsicum annuum L.). Both ${O_2}^-\;and\;H_2O_2 $ accumulated much faster during nonhost resistance when compared to the host resistance. The scavenging enzyme activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX) were also different during the host- and nonhost-incompatible interactions. CAT activity was much higher during nonhost resistance, and several new isozymes of SOD and POX were detected during nonhost resistance when compared to the host resistance. Lipoxygenase (LOX) activity was higher in host resistance than nonhost resistance during the early stages of infection. Interestingly, the nitric oxide (NO) radical accumulated equal amounts during both host and nonhost resistance at early stages of infection. Further studies are needed to determine the specific pathways underlying these differences between host and nonhost resistance responses.

Activation of Defense Responses in Chinese Cabbage by a Nonhost Pathogen, Pseudomonas syringae pv. tomato

  • Park, Yong-Soon;Jeon, Myeong-Hoon;Lee, Sung-Hee;Moon, Jee-Sook;Cha, Jae-Soon;Kim, Hak-Yong;Cho, Tae-Ju
    • BMB Reports
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    • v.38 no.6
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    • pp.748-754
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    • 2005
  • Pseudomonas syringae pv. tomato (Pst) causes a bacterial speck disease in tomato and Arabidopsis. In Chinese cabbage, in which host-pathogen interactions are not well understood, Pst does not cause disease but rather elicits a hypersensitive response. Pst induces localized cell death and $H_2O_2$ accumulation, a typical hypersensitive response, in infiltrated cabbage leaves. Pre-inoculation with Pst was found to induce resistance to Erwinia carotovora subsp. carotovora, a pathogen that causes soft rot disease in Chinese cabbage. An examination of the expression profiles of 12 previously identified Pst-inducible genes revealed that the majority of these genes were activated by salicylic acid or BTH; however, expressions of the genes encoding PR4 and a class IV chitinase were induced by ethephon, an ethylene-releasing compound, but not by salicylic acid, BTH, or methyl jasmonate. This implies that Pst activates both salicylate-dependent and salicylate-independent defense responses in Chinese cabbage.

Message in a Bottle: Chemical Biology of Induced Disease Resistance in Plants

  • Schreiber, Karl;Desveaux, Darrell
    • The Plant Pathology Journal
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    • v.24 no.3
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    • pp.245-268
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    • 2008
  • The outcome of plant-pathogen interactions is influenced significantly by endogenous small molecules that coordinate plant defence responses. There is currently tremendous scientific and commercial interest in identifying chemicals whose exogenous application activates plant defences and affords protection from pathogen infection. In this review, we provide a survey of compounds known to induce disease resistance in plants, with particular emphasis on how each compound was originally identified, its putative or demonstrated mechanism of defence induction, and the known biological target(s) of each chemical. Larger polymeric structures and peptides/proteins are also discussed in this context. The quest for novel defence-inducing molecules would be aided by the capability for high-throughput analysis of candidate compounds, and we describe some issues associated with the development of these types of screens. Subsequent characterization of hits can be a formidable challenge, especially in terms of identifying chemical targets in plant cells. A variety of powerful molecular tools are available for this characterization, not only to provide insight into methods of plant defence activation, but also to probe fundamental biological processes. Furthermore, these investigations can reveal molecules with significant commercial potential as crop protectants, although a number of factors must be considered for this potential to be realized. By highlighting recent progress in the application of chemical biology techniques for the modulation of plant-pathogen interactions, we provide some perspective on the exciting opportunities for future progress in this field of research.