Current Developments in the Detection and Control of Multi Drug Resistance

Recent Developments to Fight Multidrug Resistance (MDR) in Protozoa

Author(s): Mrinalini Roy, Sanket Kaushik, Anupam Jyoti and Vijay Kumar Srivastava * .

Pp: 141-156 (16)

DOI: 10.2174/9789815049879122010013

* (Excluding Mailing and Handling)

Abstract

This chapter focuses on the solutions to emerging multidrug resistance in the major parasitic protozoa plaguing the world. These neglected pathogens have seized the developing nations in a vice-like grip and are seeping into the industrialised world with the dramatic increase in global travel. The alarming rise in resistance to most antiparasitic drugs has left even the wealthiest nations vulnerable. Multidrug resistance occurs to give a survival advantage to the parasite; it has been hastened by the uncontrolled use of chemotherapeutics. This chapter categorises the recent developments to overcome the MDR hurdle under different approaches. The synthesis of novel organic compounds and high-throughput screenings of new chemical entities are two major approaches. Protease and topoisomerase inhibitors of parasitic protozoa prove as worthy drug targets. In-silico and proteomics-based methods also accelerate drug discovery by creating potential drug libraries specific to tropical protozoa. A costeffective and rapid method of combating drug resistance is the repurposing of licensed medicines. This approach also accounts for the established safety of drugs and high commercial availability. Molecular advancements have introduced small interfering RNAs (siRNAs) at preclinical levels as therapeutics functioning via a unique mechanism. The nanoparticle and cell-penetrating peptides (CPP) based delivery of siRNAs has facilitated a stable and low toxic way to silence genes providing pathogenicity and resistance. This will help in reversing MDR and breathing new life into the existing licensed antiprotozoal chemotherapies. 


Keywords: Antimicrobial peptides, Antiprotozoal therapeutics, Aystems biology, Drug repurposing, In-silico, Multidrug resistance, Protease inhibitors, siRNA, Synthetic organic compounds.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834522 and j.to_date >= 1739834522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 17355) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834522 and j.to_date >= 1739834522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 17355) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834522 and j.to_date >= 1739834522 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 17355)
      530μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 3372 and `b`.`banner_from_date` <= 1739834522 and `b`.`banner_to_date` >= 1739834522 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.05msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3372
      • 3: 1739834522
      • 4: 1739834522
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='8d96d86428cdea824af7ae41675d613e'
      180μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    9Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        sMFnBIswVLyVNU8gwxFKcZpP7BRZAD19n2qkHXZJ
        uc_cart_id
        8d96d86428cdea824af7ae41675d613e
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/17355" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/17355
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
        0 of 0
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        response_headers
        0 of 0
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        session_attributes
        0 of 0
        array:5 [ "_token" => "sMFnBIswVLyVNU8gwxFKcZpP7BRZAD19n2qkHXZJ" "uc_cart_id" => "8d96d86428cdea824af7ae41675d613e" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/17355" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:22:02GET/chapter/173551121911