Frontiers in Anti-Infective Drug Discovery

Volume: 8

Subtractive Genomics Approaches: Towards Anti- Bacterial Drug Discovery

Author(s): Fatima Shahid, Muhammad Shehroz, Tahreem Zaheer and Amjad Ali

Pp: 144-158 (15)

DOI: 10.2174/9789811412387120080007

* (Excluding Mailing and Handling)

Abstract

Pathogenic bacteria are evolving at a much faster rate and have the ability to acquire new antibacterial resistance patterns. The most common pathogenic bacteria are now becoming increasingly resistant to available antibiotics. The CDC has suggested to find alternative therapeutics to combat the growing antimicrobial resistance. Thanks to technological development in sequencing platforms and sophisticated bioinformatics pipelines, it now easier to analyze large-scale genomic data and propose alternative and novel treatment options. Subtractive genomics is one such approach that mines whole genomic DNA for identification of potential drug target(s). This strategy employs various computational filters using databases and online servers to screen and prioritize certain candidate proteins. Each filter analyzes the whole proteome of bacteria under study in a step-wise manner. Initially, strainspecific paralogous and host-specific homologous sequences are subtracted from the bacterial proteome to remove duplicates and prevent cytotoxicity and autoimmunity related challenges. The sorted proteome is further refined to identify essential genes involved in crucial metabolic pathways of the pathogen and thus can be used as targets for treatment interventions. Functional annotation is carried out to elucidate the involvement of these proteins in important cellular processes, metabolic pathway, and subcellular location analyses are carried out for finding the probable cellular location of the candidate proteins in the cell. Proteins with certain physicochemical properties like favorable molecular weight, hydrophobicity, and pI are rendered fine drug targets, thus filter. Importantly, the scrutinized proteins are screened against FDA approved DrugBank to identify their druggability potential. Finally, molecular docking analyses of the novel druggable targets with already present drugs are carried out. Only then, the prioritized candidate proteins can prove to be promising candidates for novel drug design and development.


Keywords: Cytoplasmic proteins, Drug targets, Membrane proteins, Metabolic pathways, Proteome, Subtractive proteomics.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
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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 <= 316587137 and j.to_ip >=316587137 )) and ((j.from_date <= 1740347468 and j.to_date >= 1740347468 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14067) 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 <= 316587137 and j.to_ip >=316587137 )) and ((j.from_date <= 1740347468 and j.to_date >= 1740347468 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14067) 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 <= 316587137 and j.to_ip >=316587137 )) and ((j.from_date <= 1740347468 and j.to_date >= 1740347468 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 14067)
      970μsalphaeurekaselec_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` = 2661 and `b`.`banner_from_date` <= 1740347468 and `b`.`banner_to_date` >= 1740347468 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.41msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 2661
      • 3: 1740347468
      • 4: 1740347468
      • 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='b6b1b27d4c9a3fbb358b372beebef22f'
      250μsalphaeurekaselec_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
    6Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        aYyOvhRUI5f77wzJlDY9sqeB1vBgUVhLmLIvjkbA
        uc_cart_id
        b6b1b27d4c9a3fbb358b372beebef22f
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/14067" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/14067
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6InpYWWg1ZTVocm1rd1JUQ1lEbDlJamc9PSIsInZhbHVlIjoiWkU2N1o5eVQ0eHBuSmVOa2F2STY5dkRVUXFjZXRBNzEreW5uMy9oTzhFbz0iLCJtYWMiOiIxNDgyNzdkN2IyNjM0ZTA1NzVhZTAyMzcxNTM1MzcyODgwOGY2ODhjMzAwNmM5YjZmOTNhYTQ4M2Q0ZmQ5MmM5IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6InpYWWg1ZTVocm1rd1JUQ1lEbDlJamc9PSIsInZhbHVlIjoiWkU2N1o5eVQ0eHBuSmVOa2F2STY5dkRVUXFjZXRBNzEreW5uMy9oTzhFbz0iLCJtYWMiOiIxNDgyNzdkN2IyNjM0" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Sun, 23 Feb 2025 21:51:08 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlByYmpiUWpSd09OLzJSK3pMRVh1TXc9PSIsInZhbHVlIjoiZmFxd3NnNTlaSnpwNytCY21DcWZlSStUVnd1ZUJwb25tdGloOUFnZklXdi9kK1dGV2diMXpaWm1lSnR1dVRvTGxEc2VPRU1vdW8reFhKSUJDdjZ0U0V0d3BXbjRuNzdHSDVuUmt4L1p2TVh0SWVIcVkrYkE2OFVnZjBMZm5wNXMiLCJtYWMiOiI1NTRhMGNiMzVjNTcwNzQ2NmRiMzI1YzM5YWIyMjkyNzAyMTNmODdmODFiNjUwYzVkOGIxYjc0MTM2NTM5MTU5IiwidGFnIjoiIn0%3D; expires=Wed, 26 Feb 2025 09:51:08 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IlByYmpiUWpSd09OLzJSK3pMRVh1TXc9PSIsInZhbHVlIjoiZmFxd3NnNTlaSnpwNytCY21DcWZlSStUVnd1ZUJwb25tdGloOUFnZklXdi9kK1dGV2diMXpaWm1lSnR1dVRvTGxEc2VPR" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkdCWC9tMWRHUTNBblA5VzNIUk5za3c9PSIsInZhbHVlIjoiR3JCOWl2Ny9qcmgwQWdBQjB3NU95R1JYVlR6YWtsdGI4VU1zL3k2NU54UFhkSVcwTXlkazJKSVhKdWY2NUZuWUxlUUNGMnBwTFpoRnhlM1RycDZkMVFxSU8xTHlsTVhzaXIwYVp2RzAvQzNQZkg4dmlaa2RHUzg5b3pQaDlOczIiLCJtYWMiOiJmZTQ3NGQ3OGFhZGIxOWY2ZTdkODc0ZDA5NjU4NjE0YTJlMzIzYTFhYmRjNGRmZDVkN2JhNzQzNWIzMWMwY2EwIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IkdCWC9tMWRHUTNBblA5VzNIUk5za3c9PSIsInZhbHVlIjoiR3JCOWl2Ny9qcmgwQWdBQjB3NU95R1JYVlR6YWtsdGI4VU1zL3k2NU54UFhkSVcwTXlkazJKSVh" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlByYmpiUWpSd09OLzJSK3pMRVh1TXc9PSIsInZhbHVlIjoiZmFxd3NnNTlaSnpwNytCY21DcWZlSStUVnd1ZUJwb25tdGloOUFnZklXdi9kK1dGV2diMXpaWm1lSnR1dVRvTGxEc2VPRU1vdW8reFhKSUJDdjZ0U0V0d3BXbjRuNzdHSDVuUmt4L1p2TVh0SWVIcVkrYkE2OFVnZjBMZm5wNXMiLCJtYWMiOiI1NTRhMGNiMzVjNTcwNzQ2NmRiMzI1YzM5YWIyMjkyNzAyMTNmODdmODFiNjUwYzVkOGIxYjc0MTM2NTM5MTU5IiwidGFnIjoiIn0%3D; expires=Wed, 26-Feb-2025 09:51:08 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IlByYmpiUWpSd09OLzJSK3pMRVh1TXc9PSIsInZhbHVlIjoiZmFxd3NnNTlaSnpwNytCY21DcWZlSStUVnd1ZUJwb25tdGloOUFnZklXdi9kK1dGV2diMXpaWm1lSnR1dVRvTGxEc2VPR" 1 => "alphaeurekaselectnet_session=eyJpdiI6IkdCWC9tMWRHUTNBblA5VzNIUk5za3c9PSIsInZhbHVlIjoiR3JCOWl2Ny9qcmgwQWdBQjB3NU95R1JYVlR6YWtsdGI4VU1zL3k2NU54UFhkSVcwTXlkazJKSVhKdWY2NUZuWUxlUUNGMnBwTFpoRnhlM1RycDZkMVFxSU8xTHlsTVhzaXIwYVp2RzAvQzNQZkg4dmlaa2RHUzg5b3pQaDlOczIiLCJtYWMiOiJmZTQ3NGQ3OGFhZGIxOWY2ZTdkODc0ZDA5NjU4NjE0YTJlMzIzYTFhYmRjNGRmZDVkN2JhNzQzNWIzMWMwY2EwIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IkdCWC9tMWRHUTNBblA5VzNIUk5za3c9PSIsInZhbHVlIjoiR3JCOWl2Ny9qcmgwQWdBQjB3NU95R1JYVlR6YWtsdGI4VU1zL3k2NU54UFhkSVcwTXlkazJKSVh" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "aYyOvhRUI5f77wzJlDY9sqeB1vBgUVhLmLIvjkbA" "uc_cart_id" => "b6b1b27d4c9a3fbb358b372beebef22f" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/14067" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-23 21:51:08GET/chapter/14067112198