{"id":11749,"date":"2023-09-28T17:21:35","date_gmt":"2023-09-28T09:21:35","guid":{"rendered":"https:\/\/docquity.com\/?post_type=articles&p=11749"},"modified":"2025-02-11T13:37:07","modified_gmt":"2025-02-11T05:37:07","slug":"hy-vong-moi-cho-cuoc-chien-voi-vi-khuan-da-khang-thuoc","status":"publish","type":"articles","link":"https:\/\/docquity.com\/vi\/articles\/hy-vong-moi-cho-cuoc-chien-voi-vi-khuan-da-khang-thuoc\/","title":{"rendered":"Hy v\u1ecdng m\u1edbi cho cu\u1ed9c chi\u1ebfn v\u1edbi vi khu\u1ea9n \u0111a kh\u00e1ng thu\u1ed1c"},"content":{"rendered":"\n

C\u00e2u chuy\u1ec7n c\u1ee7a nghi\u00ean c\u1ee9u v\u00e0 ph\u00e1t tri\u1ec3n kh\u00e1ng sinh m\u1edbi<\/strong><\/p>\n\n\n\n

\u0110a s\u1ed1 c\u00e1c kh\u00e1ng sinh \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng trong l\u00e2m s\u00e0ng \u0111\u1ec1u c\u00f3 ngu\u1ed3n g\u1ed1c t\u1eeb gi\u00e1 \u0111\u1ee1 sinh h\u1ecdc c\u1ee7a c\u00e1c s\u1ea3n ph\u1ea9m trong t\u1ef1 nhi\u00ean, \u0111\u01b0\u1ee3c ph\u00e1t hi\u1ec7n qua vi\u1ec7c s\u00e0ng l\u1ecdc vi khu\u1ea9n tr\u00fa ng\u1ee5 trong \u0111\u1ea5t [1]. C\u00e1ch ti\u1ebfp c\u1eadn n\u00e0y \u0111\u01b0\u1ee3c ph\u00e1t tri\u1ec3n b\u1edfi \u201cWaksman platform\u201d v\u00e0 mang l\u1ea1i nhi\u1ec1u th\u00e0nh t\u1ef1u trong nh\u1eefng n\u0103m 1940 \u2013 1960. Giai \u0111o\u1ea1n n\u00e0y c\u0169ng \u0111\u01b0\u1ee3c xem l\u00e0 k\u1ef7 nguy\u00ean v\u00e0ng trong nghi\u00ean c\u1ee9u v\u00e0 ph\u00e1t tri\u1ec3n kh\u00e1ng sinh. Streptomycin, vancomycin hay tetracycline \u0111\u00e3 \u0111\u01b0\u1ee3c ra \u0111\u1eddi nh\u1edd c\u00e1ch ti\u1ebfp c\u1eadn n\u00e0y. Tuy nhi\u00ean, ng\u00e0y nay bi\u1ec7n ph\u00e1p n\u00e0y kh\u00f4ng c\u00f2n m\u1ea5y hi\u1ec7u qu\u1ea3 v\u00ec h\u1ea7u h\u1ebft k\u1ebft qu\u1ea3 thu \u0111\u01b0\u1ee3c \u0111\u1ec1u l\u00e0 nh\u1eefng ho\u1ea1t ch\u1ea5t \u0111\u00e3 \u0111\u01b0\u1ee3c bi\u1ebft \u0111\u1ebfn tr\u01b0\u1edbc \u0111\u00f3. V\u1edbi t\u00ecnh h\u00ecnh hi\u1ec7n t\u1ea1i c\u1ee7a ng\u00e0nh c\u00f4ng nghi\u1ec7p nghi\u00ean c\u1ee9u v\u00e0 ph\u00e1t tri\u1ec3n thu\u1ed1c, vi\u1ec7c t\u00ecm ki\u1ebfm kh\u00e1ng sinh v\u1edbi c\u01a1 ch\u1ebf ho\u1ea1t \u0111\u1ed9ng m\u1edbi t\u1eeb nh\u1eefng nh\u00f3m vi khu\u1ea9n ch\u01b0a \u0111\u01b0\u1ee3c khai th\u00e1c l\u00e0 c\u1ea7n thi\u1ebft [2].<\/p>\n\n\n\n

G\u1ea7n \u0111\u00e2y, c\u00f4ng ngh\u1ec7 iChip \u0111\u00e3 h\u1ed7 tr\u1ee3 ti\u1ebfp c\u1eadn \u0111a d\u1ea1ng lo\u00e0i vi khu\u1ea9n ch\u01b0a \u0111\u01b0\u1ee3c nu\u00f4i c\u1ea5y, l\u00e0 c\u00f4ng ngh\u1ec7 \u0111\u00e3 mang l\u1ea1i s\u1ef1 ra \u0111\u1eddi c\u1ee7a teixobactin \u2013 kh\u00e1ng sinh \u0111\u01b0\u1ee3c ph\u00e2n l\u1eadp t\u1eeb vi khu\u1ea9n Eleftheria terrae<\/em> \u1edf trong \u0111\u1ea5t [3, 4]. Teixobactin c\u00f3 c\u1ea5u tr\u00fac h\u00f3a h\u1ecdc \u0111\u1ed9c nh\u1ea5t v\u1edbi ho\u1ea1t t\u00ednh kh\u00e1ng khu\u1ea9n t\u1ed1t [2]. Teixobactin \u1ee9c ch\u1ebf qu\u00e1 tr\u00ecnh sinh t\u1ed5ng h\u1ee3p th\u00e0nh t\u1ebf b\u00e0o c\u1ee7a vi khu\u1ea9n b\u1eb1ng vi\u1ec7c g\u1eafn k\u1ebft \u0111\u1eb7c hi\u1ec7u v\u1edbi c\u00e1c ti\u1ec1n ch\u1ea5t lipid, h\u00ecnh th\u00e0nh c\u1ea5u tr\u00fac si\u00eau ph\u00e2n t\u1eed g\u00e2y x\u00e1o tr\u1ed9n s\u1ef1 \u1ed5n \u0111\u1ecbnh m\u00e0ng [5]. B\u00ean c\u1ea1nh teixobactin, 2 kh\u00e1ng sinh v\u1edbi c\u01a1 ch\u1ebf ho\u1ea1t \u0111\u1ed9ng m\u1edbi \u0111\u01b0\u1ee3c ph\u00e2n l\u1eadp t\u1eeb nh\u1eefng vi khu\u1ea9n ch\u01b0a t\u1eebng \u0111\u01b0\u1ee3c nu\u00f4i c\u1ea5y l\u00e0 lassomycin \u2013 ch\u1ea5t \u1ee9c ch\u1ebf ClpP1P2C1 protease v\u00e0 amycobactin \u2013 ch\u1ea5t \u1ee9c ch\u1ebf SecY protein exporter [6, 7]. Vi khu\u1ea9n ch\u01b0a \u0111\u01b0\u1ee3c nu\u00f4i c\u1ea5y c\u00f3 th\u1ec3 l\u00e0 m\u1ed9t ngu\u1ed3n t\u00e0i nguy\u00ean d\u1ed3i d\u00e0o \u0111\u1ec3 khai ph\u00e1 ra nh\u1eefng h\u1ee3p ch\u1ea5t h\u00f3a h\u1ecdc m\u1edbi v\u1edbi c\u01a1 ch\u1ebf ho\u1ea1t \u0111\u1ed9ng m\u1edbi \u0111\u1ec3 nghi\u00ean c\u1ee9u v\u00e0 ph\u00e1t tri\u1ec3n nh\u1eefng kh\u00e1ng sinh th\u1ebf h\u1ec7 m\u1edbi.<\/p>\n\n\n\n

M\u1ed9t kh\u00e1ng sinh m\u1edbi \u2013 clovibactin \u2013 kh\u00e1ng sinh \u0111\u01b0\u1ee3c \u0111\u1ecbnh danh t\u1eeb vi khu\u1ea9n ch\u01b0a \u0111\u01b0\u1ee3c nu\u00f4i c\u1ea5y \u2013 \u0111\u01b0\u1ee3c cho l\u00e0 ch\u01b0a h\u1ec1 c\u00f3 vi khu\u1ea9n n\u00e0o c\u00f3 th\u1ec3 \u0111\u1ec1 kh\u00e1ng. B\u00e0i vi\u1ebft \u0111\u1ec1 c\u1eadp \u0111\u1ebfn th\u00f4ng tin c\u1ee7a clovibactin.<\/p>\n\n\n\n

\"\"H\u00ecnh 1. <\/strong>C\u1ea5u tr\u00fac h\u00f3a h\u1ecdc v\u00e0 c\u01a1 ch\u1ebf ho\u1ea1t \u0111\u1ed9ng c\u1ee7a clovibactin<\/p>\n\n\n\n

S\u1ef1 ra \u0111\u1eddi c\u1ee7a clovibactin<\/strong><\/p>\n\n\n\n

M\u00f4i tr\u01b0\u1eddng l\u00ean men vi khu\u1ea9n Eleftheria terrae ssp. carolina \u0394bat1<\/em> \u0111\u01b0\u1ee3c ph\u00e2n t\u00e1ch, m\u1ed9t h\u1ee3p ch\u1ea5t c\u00f3 kh\u1ed1i l\u01b0\u1ee3ng ph\u00e2n t\u1eed \u0111\u1ed9c nh\u1ea5t \u0111\u01b0\u1ee3c ph\u00e2n l\u1eadp. Ph\u01b0\u01a1ng ph\u00e1p ph\u00e2n t\u00edch quang ph\u1ed5 c\u1ed9ng h\u01b0\u1edfng t\u1eeb h\u1ea1t nh\u00e2n \u0111\u00e3 cho th\u1ea5y c\u1ea5u tr\u00fac h\u00f3a h\u1ecdc c\u1ee7a h\u1ee3p ch\u1ea5t n\u00e0y \u2013 m\u1ed9t depsipeptide, \u0111\u01b0\u1ee3c \u0111\u1eb7t t\u00ean l\u00e0 clovibactin (h\u00ecnh 1).<\/p>\n\n\n\n

Ho\u1ea1t t\u00ednh kh\u00e1ng khu\u1ea9n c\u1ee7a clovibactin<\/strong><\/p>\n\n\n\n

Clovibactin cho th\u1ea5y ho\u1ea1t t\u00ednh kh\u00e1ng khu\u1ea9n c\u00f3 ph\u1ed5 tr\u00ean vi khu\u1ea9n gram (+), bao g\u1ed3m Staphylococcus aureus<\/em> \u0111\u1ec1 kh\u00e1ng methicillin (methicillin-resistant S. aureus<\/em> \u2013 MRSA), c\u00e1c ch\u1ee7ng Staphylococcus aureus<\/em> \u0111\u1ec1 kh\u00e1ng daptomycin v\u00e0 \u0111\u1ec1 kh\u00e1ng trung gian vancomycin (vancomycin-intermediate-resistant S. aureus<\/em> \u2013 VISA) v\u00e0 Enterococcus faecalis<\/em> v\u00e0 Enterococcus faecium<\/em> \u0111\u1ec1 kh\u00e1ng vancomycin kh\u00f3 tr\u1ecb (enterococci \u0111\u1ec1 kh\u00e1ng vancomycin \u2013 VRE). MIC c\u1ee7a clovibactin v\u1edbi m\u1ed9t s\u1ed1 ch\u1ee7ng vi khu\u1ea9n \u0111\u01b0\u1ee3c th\u1ec3 hi\u1ec7n trong h\u00ecnh 2.<\/p>\n\n\n\n

\"\"H\u00ecnh 2. <\/strong>Ho\u1ea1t t\u00ednh kh\u00e1ng khu\u1ea9n c\u1ee7a clovibactin<\/p>\n\n\n\n

Vi\u1ebft t\u1eaft:<\/em><\/strong> Minimal inhibitory concentrations (MICs): N\u1ed3ng \u0111\u1ed9 \u1ee9c ch\u1ebf t\u1ed1i thi\u1ec3u; Glycopeptide intermediate resistant S. aureus (GISA): S. aureus \u1ee9c ch\u1ebf trung gian glycopeptide; Methicillin-sensitive S. aureus (MSSA): S. aureus nh\u1ea1y c\u1ea3m methicillin; Methicillin-resistant S. aureus (MRSA): S. aureus \u0111\u1ec1 kh\u00e1ng methicillin; Vancomycin-intermediate-resistant S. aureus (VISA): S.aureus \u0111\u1ec1 kh\u00e1ng trung gian vancomycin; Vancomycin-resistant enterococci (VRE): enterococci \u0111\u1ec1 kh\u00e1ng vancomycin.<\/em><\/p>\n\n\n\n

Clovibactin kh\u00f4ng cho th\u1ea5y \u0111\u1ed9c t\u00ednh v\u1edbi t\u1ebf b\u00e0o NIH\/3T3 v\u00e0 HepG2 c\u1ee7a \u0111\u1ed9ng v\u1eadt c\u00f3 v\u00fa \u1edf n\u1ed3ng \u0111\u1ed9 100 \u00b5g\/ml (n\u1ed3ng \u0111\u1ed9 cao nh\u1ea5t \u0111\u01b0\u1ee3c th\u1eed nghi\u1ec7m). Ho\u1ea1t t\u00ednh kh\u00e1ng khu\u1ea9n t\u1ed1t v\u00e0 \u0111\u1ed9c t\u00ednh th\u1ea5p c\u1ee7a clovibactin l\u00e0 c\u01a1 s\u1edf \u0111\u1ec3 ti\u1ebfn h\u00e0nh th\u1eed nghi\u1ec7m in vivo<\/em> c\u1ee7a clovibactin. Nghi\u00ean c\u1ee9u d\u01b0\u1ee3c \u0111\u1ed9ng h\u1ecdc \u0111\u01b0\u1ee3c ti\u1ebfn h\u00e0nh \u0111\u1ec3 \u0111\u00e1nh gi\u00e1 th\u1eddi gian ph\u01a1i nhi\u1ec5m h\u1ec7 th\u1ed1ng v\u00e0 th\u1eddi gian l\u01b0u tr\u1eef trong m\u00e1u c\u1ee7a clovibactin. Li\u1ec1u \u0111\u01a1n clovibactin (40 mg\/kg) \u0111\u01b0\u1eddng ti\u00eam t\u0129nh m\u1ea1ch \u0111\u01b0\u1ee3c th\u1eed nghi\u1ec7m tr\u00ean chu\u1ed9t. K\u1ebft qu\u1ea3 \u0111\u1ed9ng l\u1ef1c h\u1ecdc tr\u00ean chu\u1ed9t \u0111\u01b0\u1ee3c th\u1ec3 hi\u1ec7n trong b\u1ea3ng 1.<\/p>\n\n\n\n

B\u1ea3ng 1. <\/strong>T\u00ednh ch\u1ea5t \u0111\u1ed9ng l\u1ef1c h\u1ecdc c\u1ee7a clovibactin<\/p>\n\n\n\n

\"\"Hi\u1ec7u l\u1ef1c kh\u00e1ng khu\u1ea9n c\u1ee7a clovibactin \u0111\u01b0\u1ee3c ti\u1ebfn h\u00e0nh tr\u00ean chu\u1ed9t b\u1ecb nhi\u1ec5m S.aureus<\/em> \u1edf \u0111\u00f9i k\u00e8m gi\u1ea3m b\u1ea1ch c\u1ea7u. Hi\u1ec7u l\u1ef1c c\u1ee7a clovibactin kh\u00f4ng thua k\u00e9m so v\u1edbi vancomycin trong vi\u1ec7c l\u00e0m gi\u1ea3m s\u1ed1 l\u01b0\u1ee3ng vi khu\u1ea9n (h\u00ecnh 3).<\/p>\n\n\n\n

\"\"H\u00ecnh 3. <\/strong>Hi\u1ec7u l\u1ef1c c\u1ee7a clovibactin so v\u1edbi vancomycin<\/p>\n\n\n\n

C\u01a1 ch\u1ebf ho\u1ea1t \u0111\u1ed9ng c\u1ee7a clovibactin<\/strong><\/p>\n\n\n\n

Clovibactin \u1ee9c ch\u1ebf to\u00e0n b\u1ed9 qu\u00e1 tr\u00ecnh t\u1ed5ng h\u1ee3p th\u00e0nh t\u1ebf b\u00e0o c\u1ee7a vi khu\u1ea9n b\u1eb1ng c\u00e1ch nh\u1eafm \u0111\u00edch tr\u00ean c\u1ea3 3 c\u1ea5u tr\u00fac quan tr\u1ecdng: C55<\/sub>PP, lipid II v\u00e0 lipid IIWTA<\/sub>. Clovibactin g\u1eafn k\u1ebft v\u1edbi th\u00e0nh ph\u1ea7n pyrophosphate c\u1ee7a t\u1ea5t c\u1ea3 c\u00e1c ti\u1ec1n ch\u1ea5t n\u00e0y. Clovibactin bao v\u00e2y xung quanh c\u00e1c pyrophosphate, gi\u1ed1ng nh\u01b0 c\u1ea5u tr\u00fac l\u1ed3ng bao quanh c\u00e1c \u0111\u00edch ho\u1ea1t \u0111\u1ed9ng l\u00e0 C55<\/sub>PP, lipid II v\u00e0 lipid IIWTA<\/sub>. Th\u1ef1c ch\u1ea5t c\u00e1i t\u00ean clovibactin \u0111\u01b0\u1ee3c h\u00ecnh th\u00e0nh t\u1eeb t\u00ean Hy L\u1ea1p klouvi<\/em> c\u00f3 ngh\u0129a l\u00e0 c\u00e1i l\u1ed3ng [2]. Kh\u00eda c\u1ea1nh quan tr\u1ecdng trong c\u01a1 ch\u1ebf ho\u1ea1t \u0111\u1ed9ng c\u1ee7a clovibactin \u0111\u00f3 l\u00e0 clovibactin ch\u1ec9 g\u1eafn k\u1ebft v\u1edbi c\u00e1c pyrophosphate kh\u00f4ng th\u1ec3 bi\u1ebfn \u0111\u1ed1i v\u00e0 l\u00e0 ti\u1ec1n ch\u1ea5t th\u01b0\u1eddng g\u1eb7p c\u1ee7a th\u00e0nh t\u1ebf b\u00e0o vi khu\u1ea9n. Kh\u00f4ng nh\u1eefng v\u1eady, clovibactin c\u00f2n b\u1ecf qua th\u00e0nh ph\u1ea7n peptide c\u00f3 th\u1ec3 bi\u1ebfn \u0111\u1ed5i c\u1ee7a c\u00e1c \u0111\u00edch ho\u1ea1t \u0111\u1ed9ng. Do v\u1eady, vi khu\u1ea9n kh\u00f3 c\u00f3 th\u1ec3 bi\u1ebfn \u0111\u1ed5i \u0111\u1ec3 \u0111\u1ec1 kh\u00e1ng. Trong c\u00e1c nghi\u00ean c\u1ee9u \u0111\u00e3 \u0111\u01b0\u1ee3c ti\u1ebfn h\u00e0nh v\u1edbi clovibactin, ch\u01b0a c\u00f3 m\u1ed9t vi khu\u1ea9n \u0111\u1ec1 kh\u00e1ng n\u00e0o \u0111\u01b0\u1ee3c ph\u00e1t hi\u1ec7n [2].<\/p>\n\n\n\n

K\u1ebft lu\u1eadn<\/strong><\/p>\n\n\n\n

V\u00ec c\u00e1c nghi\u00ean c\u1ee9u v\u1ec1 clovibactin m\u1edbi ch\u1ec9 \u0111\u01b0\u1ee3c ti\u1ebfn h\u00e0nh tr\u00ean \u0111\u1ed9ng v\u1eadt, do v\u1eady, \u0111\u1ed9c t\u00ednh c\u0169ng nh\u01b0 hi\u1ec7u l\u1ef1c c\u1ee7a clovibactin v\u1eabn c\u00f2n l\u00e0 \u1ea9n s\u1ed1 tr\u00ean ng\u01b0\u1eddi. \u0110\u1ec3 \u0111\u01b0a v\u00e0o \u1ee9ng d\u1ee5ng tr\u00ean l\u00e2m s\u00e0ng, clovibactin v\u1eabn c\u00f2n m\u1ed9t ch\u1eb7ng \u0111\u01b0\u1eddng d\u00e0i ph\u1ea3i tr\u1ea3i qua. Tuy nhi\u00ean, k\u1ebft qu\u1ea3 nghi\u00ean c\u1ee9u in vivo <\/em>s\u01a1 b\u1ed9 \u0111\u00e3 cho th\u1ea5y clovibactin l\u00e0 m\u1ed9t hy v\u1ecdng m\u1edbi cho cu\u1ed9c chi\u1ebfn ch\u1ed1ng l\u1ea1i vi khu\u1ea9n \u0111\u1ec1 kh\u00e1ng kh\u00e1ng sinh.<\/p>\n\n\n\n

T\u00e0i li\u1ec7u tham kh\u1ea3o<\/strong><\/p>\n\n\n\n

    \n
  1. Lewis, K. (2020). The science of antibiotic discovery. Cell 181, 29\u201345. https:\/\/doi.org\/10.1016\/j.cell.2020.02.056<\/a>.<\/li>\n\n\n\n
  2. Shukla R, Peoples AJ, Ludwig KC et al. An antibiotic from an uncultured bacterium binds to an immutable target. Cell. 2023 Sep 14;186(19):4059-4073.e27. doi: 10.1016\/j.cell.2023.07.038.<\/li>\n\n\n\n
  3. Nichols, D., Cahoon, N., Trakhtenberg, E.M., Pham, L et al. Use of ichip for high-throughput in situ cultivation of “uncultivable” microbial species. Appl. Environ. Microbiol. 76, 2445\u20132450. https:\/\/doi.org\/10.1128\/AEM. 01754-09.<\/li>\n\n\n\n
  4. Ling, L.L., Schneider, T., Peoples, A.J., et al. A new antibiotic kills pathogens without detectable resistance. Nature 517, 455\u2013459. https:\/\/doi.org\/10.1038\/nature14098.<\/li>\n\n\n\n
  5. Shukla, R., Lavore, F., Maity, S., et al. Teixobactin kills bacteria by a two-pronged attack on the cell envelope. Nature 608, 390\u2013396. https:\/\/doi.org\/10.1038\/s41586-022-05019-y.<\/li>\n\n\n\n
  6. Gavrish, E., Sit, C.S., Cao, S. et al. Lassomycin, a ribosomally synthesized cyclic peptide, kills Mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2. Chem. Biol. 21, 509\u2013518. https:\/\/doi.org\/10.1016\/j.chembiol.2014.01.014.<\/li>\n\n\n\n
  7. Quigley, J., Peoples, A., Sarybaeva, A. et al. Novel antimicrobials from uncultured bacteria acting against Mycobacterium tuberculosis. mBio 11. e01516\u2013e01520. https:\/\/doi.org\/10.1128\/mBio. 01516-20.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    C\u00e2u chuy\u1ec7n c\u1ee7a nghi\u00ean c\u1ee9u v\u00e0 ph\u00e1t tri\u1ec3n kh\u00e1ng sinh m\u1edbi \u0110a s\u1ed1 c\u00e1c kh\u00e1ng sinh \u0111\u01b0\u1ee3c s\u1eed d\u1ee5ng trong l\u00e2m s\u00e0ng \u0111\u1ec1u c\u00f3 ngu\u1ed3n g\u1ed1c t\u1eeb gi\u00e1 \u0111\u1ee1 sinh h\u1ecdc c\u1ee7a c\u00e1c s\u1ea3n ph\u1ea9m trong t\u1ef1 nhi\u00ean, \u0111\u01b0\u1ee3c ph\u00e1t hi\u1ec7n qua vi\u1ec7c s\u00e0ng l\u1ecdc vi khu\u1ea9n tr\u00fa ng\u1ee5 trong \u0111\u1ea5t [1]. C\u00e1ch ti\u1ebfp c\u1eadn …<\/p>\n

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