Frontiers in Clinical Drug Research-Anti Infectives

Volume: 1

The Potential of Bacteriophage Lysins in the Treatment of Gram- Positive Bacteria Including Multidrug Resistant Bacteria

Author(s): Raymond Schuch, Vincent A. Fischetti, Hoonmo L. Koo and David B. Huang

Pp: 308-337 (30)

DOI: 10.2174/9781608058549114010010

* (Excluding Mailing and Handling)

Abstract

Almost two million Americans per year develop hospital-acquired infections, resulting in 99,000 deaths, the vast majority of which are due to antibiotic-resistant pathogens. Because of the pressing public concern over the emergence and global spread of MDR Gram-positive bacteria, as well as the serious and life threatening nature of these diseases and the limitations of current available antibiotics, global efforts are now focused on the development of novel and alternative antibacterial. One very promising new class of antimicrobial agents includes members of a widespread family of bacteriophage-encoded, bacterial cell wall-hydrolytic enzymes, or lysins. Lysins represent a new class of antibacterial agents against Gram-positive bacteria including multidrug-resistant bacteria, with a mechanism of action distinct from antibiotics. In this review, we will describe the nature of phage lysins, how they are distinguished from antibiotics, and how they may be applied to human medicine. Finally, we will discuss the hurdles to developing a new antimicrobial class and bringing it from the lab bench to the market.


Keywords: Bacteriophage, Gram-positive bacteria, lysins, Multidrug Resistant Bacteria, multidrug-resistant.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 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 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 <= 314378200 and j.to_ip >=314378200 )) and ((j.from_date <= 1739848484 and j.to_date >= 1739848484 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6439) 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 <= 314378200 and j.to_ip >=314378200 )) and ((j.from_date <= 1739848484 and j.to_date >= 1739848484 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6439) 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 <= 314378200 and j.to_ip >=314378200 )) and ((j.from_date <= 1739848484 and j.to_date >= 1739848484 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 6439)
      590μsalphaeurekaselec_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` = 1507 and `b`.`banner_from_date` <= 1739848484 and `b`.`banner_to_date` >= 1739848484 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.04msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 1507
      • 3: 1739848484
      • 4: 1739848484
      • 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='645ccf7b8534556cacd335b1f6b00f85'
      200μsalphaeurekaselec_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
    5Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        bYi7gpnlyLZzR5X6AjnpoqXRT1SeaGmJKr7nOtXt
        uc_cart_id
        645ccf7b8534556cacd335b1f6b00f85
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/6439" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/6439
        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:16 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "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
        []
        
        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 => "Tue, 18 Feb 2025 03:14:44 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkIwYzhQWnZyalFFaHNsWkxadkJVMVE9PSIsInZhbHVlIjoiWXowcSsvaUNnSllzK3hKZTRSaEUvZzlsUTNXcW5Zd3EvNUtjZnN5QU5BcGlYUWJCR3NIa0xCNk03MVZQa2wvblRwd0ZzOURqc1lqZjk2V21kTW0rK0FBcEVYR1hSNlJHakJjMUlZVnhCaE5Cb1VGanR4K201bFB3R1drWUhVbVciLCJtYWMiOiJmOWNkNzNmY2RkMjM0M2E4NzU0M2Q0Nzc3NDg3NTY5ZTY3MjMxZTFlYWIxZTRmMDhmMDk1YzE0NGNlMTQyNDkzIiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 15:14:44 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IkIwYzhQWnZyalFFaHNsWkxadkJVMVE9PSIsInZhbHVlIjoiWXowcSsvaUNnSllzK3hKZTRSaEUvZzlsUTNXcW5Zd3EvNUtjZnN5QU5BcGlYUWJCR3NIa0xCNk03MVZQa2wvblRwd0ZzO" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ind1cmxCR2FaYktqSVhMQ2ZOUG4vNWc9PSIsInZhbHVlIjoiWjdWelN0aVFwbzNXQldSQXpBbXp2MmhGUjI2aGRhVTZZNzBnbUplQWpkYlNmeGF1VFJINEhYNGl4eXZZTzU2c05melEvQ0tnTXFlL2VERjMvY2ZOa2ErZzBCd1YxS3IzZ3VIcGdzbjlwbDVKeGEwNlJCRXRRYkt0a3BDRUl5UmEiLCJtYWMiOiJmYWE0ODY4MjI4OTY4OGY0MDgyMjgzZGI0YWEzOTI2NzVkODk0ZjI0NDA3MmRhZDE4YTEyNGY2NDg5NTBiZDc0IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Ind1cmxCR2FaYktqSVhMQ2ZOUG4vNWc9PSIsInZhbHVlIjoiWjdWelN0aVFwbzNXQldSQXpBbXp2MmhGUjI2aGRhVTZZNzBnbUplQWpkYlNmeGF1VFJINEhYNGl" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IkIwYzhQWnZyalFFaHNsWkxadkJVMVE9PSIsInZhbHVlIjoiWXowcSsvaUNnSllzK3hKZTRSaEUvZzlsUTNXcW5Zd3EvNUtjZnN5QU5BcGlYUWJCR3NIa0xCNk03MVZQa2wvblRwd0ZzOURqc1lqZjk2V21kTW0rK0FBcEVYR1hSNlJHakJjMUlZVnhCaE5Cb1VGanR4K201bFB3R1drWUhVbVciLCJtYWMiOiJmOWNkNzNmY2RkMjM0M2E4NzU0M2Q0Nzc3NDg3NTY5ZTY3MjMxZTFlYWIxZTRmMDhmMDk1YzE0NGNlMTQyNDkzIiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 15:14:44 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IkIwYzhQWnZyalFFaHNsWkxadkJVMVE9PSIsInZhbHVlIjoiWXowcSsvaUNnSllzK3hKZTRSaEUvZzlsUTNXcW5Zd3EvNUtjZnN5QU5BcGlYUWJCR3NIa0xCNk03MVZQa2wvblRwd0ZzO" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ind1cmxCR2FaYktqSVhMQ2ZOUG4vNWc9PSIsInZhbHVlIjoiWjdWelN0aVFwbzNXQldSQXpBbXp2MmhGUjI2aGRhVTZZNzBnbUplQWpkYlNmeGF1VFJINEhYNGl4eXZZTzU2c05melEvQ0tnTXFlL2VERjMvY2ZOa2ErZzBCd1YxS3IzZ3VIcGdzbjlwbDVKeGEwNlJCRXRRYkt0a3BDRUl5UmEiLCJtYWMiOiJmYWE0ODY4MjI4OTY4OGY0MDgyMjgzZGI0YWEzOTI2NzVkODk0ZjI0NDA3MmRhZDE4YTEyNGY2NDg5NTBiZDc0IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Ind1cmxCR2FaYktqSVhMQ2ZOUG4vNWc9PSIsInZhbHVlIjoiWjdWelN0aVFwbzNXQldSQXpBbXp2MmhGUjI2aGRhVTZZNzBnbUplQWpkYlNmeGF1VFJINEhYNGl" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "bYi7gpnlyLZzR5X6AjnpoqXRT1SeaGmJKr7nOtXt" "uc_cart_id" => "645ccf7b8534556cacd335b1f6b00f85" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/6439" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-18 03:14:44GET/chapter/6439112197