缁哄剁浠ｆ蹇 - 瀛 - 涓楠诲缃锛妫楠诲涓涓ㄦ风绔
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缁哄剁浠ｆ蹇
浣锛&& ユ锛&& 甯堕达 19:19:29&&瑰绘帮
稿绀猴ㄧх缁绱骞存ユх剧娌荤复涓澶ч鹃[1][2]锛缁瀵规绫绘╀骇э涔跺澶绉瀛寮╄绉板绱ㄤ复搴搴缁瓒ヨ骞裤瀵圭哄跺ㄥ浠ㄦ娴虹绛归㈢拌灞浣绠瑕缁艰堪
规 绂缓榫宀╁绗婚& 364000
& 瑕 &ㄧх缁绱骞存ユх剧娌荤复涓澶ч鹃[1][2]锛缁瀵规绫绘╀骇э涔跺澶绉瀛寮╄绉板绱ㄤ复搴搴缁瓒ヨ骞裤瀵圭哄跺ㄥ浠ㄦ娴虹绛归㈢拌灞浣绠瑕缁艰堪&&
缁у涓猴锛1锛澶╃舵绐浜х虫蹭浼哄浠瀵肩灞浜绉ц濡虹蜂集骇蜂集浜х辨蹭浠瀵肩绱讹瀵规皑瑗挎缇ц瑗挎锛2锛璐ㄧ浠瀵肩э崇寰浜辫川绮浣朵澶DNA娈碉寸缁舵甯哄浜ㄤ复搴涓瑕颁
锛涓锛尾拌虹被╄
瀵刮插拌虹被绱哄朵富瑕锛浜х尾拌洪讹绱缁斤PBP锛浣ㄤ规瑰浜х扮瀵刮插拌虹被绱涓PBP锛╁伴存х澶ч浣涓诲ㄥ绯荤灏绱娉靛鸿澶PBPs瑰╁版虫ц尾锛拌虹被绱涓昏哄讹尾锛拌洪舵╁版存ф尾锛拌虹被绱哄躲
锛浜锛尾拌洪朵瀵肩缁
尾拌洪舵╁ㄎ插拌虹被绱搴ㄤ复搴渚垮凡锛瀹骞朵挎蹇锛涓哄芥按瑙Ｎ插拌恒╁伴虫ц尾拌洪跺娉扮澶锛╁伴存ц尾拌哄娉拌ㄩ撮[3]杩Bush存扮缁剁瀛缁剁规у姘磋В搴╃瑰ヨ琛绫汇瑙涓琛
锛1锛尾拌虹浣ㄦ哄讹
尾拌烘绫讳技浜澹浣借绯介帮D涓姘ㄩ板猴D锛涓姘ㄩ告绫讳技浣锛戒PBPs尾拌洪朵稿搴锛尾拌虹╋PBPs尾拌洪剁杩缁板浣ㄥ遍板轰ㄥ搴锛尾拌虹浜叉告诲讳娇寮锛骞跺舰杩歌涔伴朵腑翠锛甯PBP尾拌洪剁涓昏哄ㄤ板哄涓锛杩涓昏涓哄浠姘村瀛渚璧т瀵刮插拌洪舵ヨ锛姘村瀛浜叉告诲诲瀛锛瀹借姘磋В涔伴朵腑翠娇跺锛骞堕疚插拌洪ㄥ锛缁浜хс瀵PBPヨ锛涔伴朵腑翠瀵规按瀛浜插诲讳锛涔伴朵腑翠涓借姘磋В姘磋В寰浠浣PBP澶辨椿
锛2锛╁伴虫ц尾拌洪朵瀵肩缁
ㄩ绱G搴ㄤ复搴涓涔锛尾拌洪朵究ㄨ¤涓箍娉甯90锛浠ヤ榛茶¤涓尾拌洪跺浜Bush绫荤2a缁涓╁伴存ц尾拌洪朵锛灏界复瀵刮插拌洪剁ǔ瀹绱╂у锛骞存ラ榛茶¤涓浜插拌洪躲瀵归绱榛茶¤浠跺绱锛濡瑗挎叉哀瑗挎澶タ绛锛澶村绱纰抽剁被绱榛茶¤尾拌洪剁浜х甯告璇卞锛辨充涓哄锛blablaR1blaR2bla缂涓绉跺瀛锛瀵刮插拌洪剁哄blaZ杞杩琛璐璋锛blaR1缂BlaR1涓澶哄ㄦユ尾拌虹被╋涓涓哄璐璐ｄ骇涓绉淇″瀵艰blaZ讹blaR2哄涓璋尾拌洪剁琛ㄨ揪锛舵哄朵
锛3锛╁伴存ц尾拌洪朵瀵肩缁
灏界╁伴存ц绉浜澶绉讹TEM锛1SHV锛1ぇ甯虹蜂集涓涓昏澶瑙躲杩浜甯骞挎跺浜Bush绫2b缁锛辫川绮浠瀵硷杩杞杞绛褰㈠娇哄ㄧ涓╂ｏ版按瑙ｉ绱绐璋卞ご瀛㈣绱讹浣涓芥按瑙ｅ箍璋辩姘т哄ご瀛㈣绱澶撮绱纰抽剁被绱锛充娇杩浜惰搴〃杈句涓戒瀵肩瀵逛杩版绱浣瀵艰寸瀵归舵跺
20涓绾80骞翠唬锛涓浠ｅご瀛㈣绱涓村搴澶骞存ヤ寸ǔ瀹TEM锛1SHV锛1剁跺蹇绐姝ヤ锛骞寸变涓ょ剁浜浣圭绐褰㈡绉瓒骞胯氨尾拌洪跺ㄤ颁锛杩浜朵瀵肩缁瀵归绱涓浜涓浠ｅご瀛绱浠ュ绱浣瀵瑰ご绱纰抽剁舵跺锛灞浜Bush绫2b缁浠ESBL瀛缁锛舵椿тㄤ逛姘ㄩ革70浣浜卞娈垫皑洪镐瀹搴存搴尾拌虹被绱杩ュ搴ㄦ借舵按瑙ｃESBL绐浣逛浜杩颁瀹搴ㄥ达宸插绉ESBL剁浣逛富瑕涓TEM锛104锛0浣瑰SHV锛179锛238锛240浣癸朵腑浣逛腑浠讳圭绐藉瀵艰村浣绉澧澶э浣垮瀛缁杈澶х涓浠ｅご瀛㈣绱藉杩ワㄦ虹涓104240绛浣圭绐灏跺涓浠ｅご瀛㈣绱浜插澧寮猴浠杩涓姝ユ楂舵按瑙ｆ澶绐浣逛舵按瑙ｆ涔涓锛濡238浣圭绐涓昏淇杩跺澶村昏姘磋В锛240104绛浣圭绐涓昏淇杩跺澶村浠剁姘磋В锛浠ユ绱浣跨ㄦ典锛ESBL绫诲ㄤ藉板烘
XTX锛M绯诲ESBL骞存ュㄤ拌TEMSHV璧锋ESBL锛CTX锛M1锛10Toho锛1Toho锛2锛瀹浠涓昏瑰澶村昏姘磋В寮猴瀵瑰ご瀛舵按瑙ｅ寮憋姝や澶楠涓骇姝ら剁父瀵瑰ご瀛㈠昏瀵瑰ご瀛惰涓浠ｅご瀛㈣绱骞挎浣跨ㄥ璧风浜х澶绉扮尾拌洪讹朵腑浠ヨ骞胯氨尾拌洪舵烽瑕锛涓昏辫绉缁锛灏ゅ跺ぇ甯虹蜂集浜х锛澶у辩TEM锛1哄SHV锛1哄绐褰㈡锛澶板涓何插拌洪舵跺锛濡缁撮革涓宸村宸村躲瀹浠ユ按瑙ｉ绱绫汇涓浠ｃ浜浠ｃ涓浠ｅご瀛㈣绱姘ㄦ插锛瀵艰寸瀵圭涓浠ｃ绗浠ｅご瀛㈣绱垮¤タ瑗挎姘ㄦ插瓒ｇ杩浜跺ぇ澶板琚稿宸村讹蜂集渚澶锛澶撮绱纰抽褰卞[3][13][14]变跺浼у瀵逛浠ｅご瀛㈣绱琛ㄧ寮璧疯瀵兼不锛琚涓烘╁版存ф涓遍╃舰寮[15]锛涓瀹浜х浣挎不村伴撅╃╄存寸锛澶ㄤ哄瑰娌荤锛ESBL虫х╁伴存ф搴ㄦュ娉ㄦ绀哄荤跨ㄎ诧拌虹被┿ESBL涓昏ㄨ虹蜂集澶ц甯涓虹锛跺ㄥ涓ㄦ娴琛濂涓[13][16][17]褰浜ESBL缁ㄨ不澶辫触讹搴ESBL浜х锛垮浣跨ㄩゅご绱″反硅戒互澶跺澶村绱[18]
AmpC剁哄讹
AmpC舵辨蹭浠瀵肩尾拌洪讹灞浜Bush绫1缁锛C绫伙锛ㄨ剁舵涓缁浜х姝ょ剁灏锛浣浜缁濡存寮姘告┘告绛ㄎ插拌虹被绱锛灏ゅ舵ご瀛㈣タ浜洪藉缁撮革浣ㄤ澶ч瀵AmpC剁浜х锛涓惰哄绐寰楂锛绐浣块舵缁ぇ骇锛瀵艰寸瀵归ょ⒊剁被涔澶尾拌虹被绱AmpC剁璇卞哄跺澶锛辨涓缁哄锛ampCampRampDampG锛骞朵缁澹借绯寰炽杩骞存ユ哄宸插濮璐ㄧ╂ｏ缁涓村甯ユ翠弗宄荤杩骞翠灏拌川绮浠瀵肩AmpC跺ㄤ藉琚AmpC跺浜Class C绫婚[3]绉板ご瀛㈣绱讹瀹Bush1绫晃插拌洪剁稿浠ｈ〃锛芥按瑙ｉ绱绫伙涓浠ｃ浜浠ｅ涓浠ｅご瀛㈣绱绫诲绫伙涓琚缁撮告讹浣澶璇楠灏借瀵肩浜AmpC[19]锛宸村浠宸村舵甯告[20]锛浣纭奸哥被╁姘瑗挎浣澶杈濂界朵ㄣAmpC跺涓鸿瀵煎锛婚缁浜у璐ㄧ缁澶у伴╁伴存ф藉锋浜хAmpC剁藉锛甯告典骇堕灏锛ㄤ复搴涓骞朵褰㈡浣涓婚AmpC朵骇哄绐锛缁灏卞缁浜AmpC讹虹瀵圭澶у拔插拌烘绱姝ゅ杩搴娉ㄦ板ㄤ缁璁や负浜AmpC剁灞缁涓ESBL藉苟涓灏瑙锛缁涓跺锋楂浜AmpC跺浜ESBL藉锛惰у朵弗
璇卞AmpC讹褰缁瑙璇卞尾拌虹被绱讹蹭ampC哄琚哄婚讹浜ч跺浜虹嚎姘村钩褰浣跨ㄦ璇卞绱娌荤讹浜х浜剁婚璞°AmpC哄辫〃杈撅浣垮缁朵骇杩尾拌洪躲涓ゆ绱锛澶у版典浜ч舵按骞虫按娓㈠板虹嚎姘村钩涓村搴ㄎ插拌虹被绱绘缁缁澹浜戒氦妗ヨ锛寮璧疯借绯绱涔憋浜х澶ч借绯褰╁伴存цㄨ川撮娴涓借绯娈电杩AmpD藉惊╃ㄨ藉讹ㄦ璺ㄨ杞绯荤AmpG藉浼借借绯娈电烘淇″锛浣AmpR藉舰婵娲诲锛婵娲ampC哄杞ampR哄杞锛璇卞缁浜хAmpC躲澶ц甯AmpC朵按骞宠〃杈撅瀹缂哄ampR哄涓借瀵间骇[21]
婚缁浜AmpC讹ㄤ骇璇卞AmpC剁╁伴存ц涓杈楂棰璋哄绐锛璋哄浣ㄥ版[22]锛AmpD璋哄绐浜х缂洪风AmpD斤浣胯婚缁浜AmpC讹浜浜х楂璇卞娓╁害AmpC[23]
璐ㄧAmpC讹20涓绾80骞翠唬浠ュ锛AmpC跺版ラ涓烘蹭锛20涓绾80骞翠唬璁稿瀹澶ч娇ㄤ浠ｅご瀛㈣绱涓AmpC剁浜х瀵崇郴璐ㄧAmpC剁虹涓ご绱锛濡澶村瑗夸澶村垮锛尾拌洪舵跺澶绱浣跨ㄩ澶浜х╁涓瀹崇郴锛浠瀛澶у缁绛电广规х甯哥被浼间蹭讹杩绉惰瓒骞胯氨尾拌洪舵村箍娉氨锛涓介舵跺绫荤村[2425]
1988骞达Papanicolaou绛棣娆″ㄨ虹蜂集璐ㄧ涓板ご瀛㈣绱讹杩绉у浠ヨ浆绉伙骞朵存ampC哄婧1994骞达ㄥ冲版告┘告涓哄甫澶村绱剁川绮锛浠ヨ浆绉昏冲ぇ甯虹蜂集涓骞剁浜хAmpC讹褰㈡璐ㄧAmpC讹澧浜浼璐ㄧ浠瀵肩AmpC剁绫讳ㄤ板锛宸插浜26绉璐ㄧAmpC[25]
20涓绾80骞翠唬╂浠ユユ扮尾拌洪剁被绱骞挎浣跨浜AmpC剁╁伴存ф宸查娓涓哄婚㈡娴琛[4]1978骞撮娆℃ラ浜搴ㄦ扮尾拌虹被绱杩绋涓轰骇楂姘村钩蹭剁寮[26]锛瀹涔褰尾拌虹被绱锛や哄瑰澶锛杩绉у凡ㄨ灞寮冲版告┘告╂硅灞绮璐ㄦ疯缁垮绛涓村绂绘腑ラ锛骞舵姣绉扮澶村绱绫汇ㄥ绱绫诲姘ㄦ插[27]杩绫绘ラ澶у版灞缁寮璧风ㄧ斤灞婚㈡琛5锛7锛锛ICU锛甯歌煎搁绗浣锛灏胯矾绗浣锛激绗浣[28]朵腑甯歌存浜ф锛瑰瀛ㄤ互涓遍╁绱讹濡挎浣灏ゅICU锛锛涓ラ虹剧锛绉躲楂榫瀵肩瑁缃绱浣跨ㄧ灞娴琛涓昏ㄥぇ娇ㄥご瀛㈣绱朵骞胯氨尾拌虹被绱跨ょ挎扮裤蹇绉ICU娴琛澶绉缁ユ浜浜鸿韩缇ゃ姝ｆ变娇ㄥ扮澶村绱褰㈡╂у锛灞缁娓涓鸿涓浼胯锛缁璁稿浜烘涓浠浜AmpC剁绉缁ㄥ婚㈢娴琛涓瓒匡涓杩浜缁褰㈡澶瓒夸涓1991骞达Chow绛[27]瀵129渚骞翠汉绌跺锛ㄨ灞缁寸琛涓浣跨ㄧ涓浠ｅご瀛㈣绱娌荤姣浣跨ㄦ皑虹风被朵尾拌虹被娌荤村瀵艰村х浜х杩涓昏涓扮澶村绱浣跨ㄥ锛浠ュ婚㈢瑙妯″浜烘板稿炽浣杩绉瓒挎浠ユ瑰锛褰缁姝㈠ご瀛㈣绱绫荤浣跨ㄦ讹浜ц瀵奸剁绉缁娴琛虹[27]
2PBP瑰浠瀵肩缁
绱缁斤PBP锛浣浜缁璐ㄨ澶澹锛ㄧ缁澹借绯璧疯浆介躲杞烽躲介惧跺缇у鸿介剁浣ㄧ涓绯诲讹瀹浠插拌虹被绱浣ㄩ朵涔缁藉锋3锛8绉PBP锛跺藉浠ユ板琛ㄧず锛濡PBP123绛锛锛瀛澶ф板瓒灏娉ㄦㄤ灞绉缁涓灏界藉板稿锛浣瀹浠苟涓涓瀹稿炽尾拌虹被绱涓锋澶涓ㄧ浣ㄩ朵锛涓2锛4涓PBP瀛蹇[3]
锛1锛╁伴虫цPBP瑰浠瀵肩缁
PSP瑰寰扮瀵规绱浣翰PBP韩淇グ瀵艰村绱浜插涓PBP锛涓昏ㄨ¤涓涓昏ㄨ虹剧涓叉哀瑗挎榛茶¤锛MRSA锛瀵规尾拌虹被绱跺变寰浜ヨ捣婧DNA缂扮尾拌PBP锛瀹辨蹭mecA哄缂锛琚藉涓PBP2a
MecA哄琛ㄥ琛ㄨ揪澶绉绱褰卞锛PH娓╁害娓с涓娓歌搴朵涓稿虫蹭哄浜MRSAmecA哄涓娓稿ㄧ璋哄mecR1mecI锛跺藉插拌洪剁璋哄blaR1blaI 镐技锛瀵mecA琛ㄨ揪杩琛璐璋MecA哄杞锛PBP2a琛ㄨ揪涓绉褰㈠锛1锛璇卞缁〃杈惧锛姝ゅMRSA缂哄mecR1锛mecI哄尾拌洪惰川绮锛锛2锛宠瀵煎锛姝ゅMRSA缂哄mecR1锛mecI哄锋尾拌洪惰川绮锛杩尾拌洪剁璋哄blaR1blaI璋mecA琛ㄨ揪锛锛3锛寤惰琛ㄨ揪锛姝ゅMRSA锋mecR1锛mecI哄锛惰уㄧ叉哀瑗挎璇卞48灏舵藉琛ㄨ揪锛涓村甯歌楠甯歌灏姝ゅゆ负锛姝ゅ锋瑕涓村锛澶锛mecA哄澶叉哀瑗挎涓fem哄锛femABCDEF绛锛琛ㄨ揪炽Fem芥存存涓缁澹╁锛涓褰卞PBP2a锛浣剁己澶卞瀵艰寸瀵圭叉哀瑗挎ч浣
虹剧涓浜х尾拌洪讹跺尾拌虹被绱变PBP锛涓昏PBP2锛瑰瀵艰村尾拌虹浜插浣虹剧6绉PBP锛1a1b2a2x2b3锛锛堕绱蹭pbq哄寮杈澶э绉颁负宓浣哄锛涓哄稿ㄥ哄芥歌绉杞ョ哄虹剧涓缁杩绋锛涓浼瀵艰翠按骞宠楂姘村钩涓pbq哄杩缁缁锛濡瀵瑰箍璋卞ご瀛㈣绱PBP1a2x瑰澶ㄤ绱╀剁浣逛涓锛姝ゅ骞胯氨绱苟涓涓瀹瀵归绱
绮灞瀵逛按骞抽绱烘变锋绱浣翰PBP5锛绮涓父瑙楂姘村钩PBP5杩骇姘ㄥ洪哥炽
锛2锛╁伴存цPBP瑰浠瀵肩缁
PBP瑰浠瀵肩缁ㄩ╁伴存ц涓灏瑙锛涓昏ㄩ缁垮娴琛娣濂搁涓ㄦ寮辩被涓ㄦ濂锛TEM锛浜х涓蹭″浠瀵肩楂姘村钩绱翰PBP12浜х炽
3澶娓ч浣涓诲ㄥ瀵艰寸尾拌鸿
杩绉富瑕瑙浜╁伴存ц╁伴存ц澶瀵刮插拌虹被绱绉灞锛绱娴娓わ姘磋В锛涔村钩琛″冲浜缁ㄥぇ甯朵存ц涓插拌虹被绱涓昏变翰姘寸藉杩澶锛冲浜х涓ょ藉锛OmpFOmpC变瀵艰OmpF/OmpC瑰琛ㄨ揪灏浣跨瀵瑰绉尾拌虹被绱т缁垮瀵瑰绉尾拌虹被绱烘э挎浠ユュ杩绉у缁涓鸿锋浣уㄥ凡璁よ拌绉ф变介璧涓诲ㄥ绯荤[9锛10]锛MexAB锛OprM锛浣у浣ㄧ缁锛杩璧剧ずMexAB锛OprM绯荤杩澶存浠瀵煎尾拌虹被绱
瀵逛瀵肩澶х涓诲ㄥ娉电绌跺璧蜂10骞村瀵瑰ぇ甯缁垮澶绱绌[9]杩骞寸绌惰璁稿╁伴虫х╁伴存ф缁瀛ㄨ介璧у绯荤锛浣胯浣╅灏界缁富ㄥ杞浣绉绫讳澶锛浣绌舵剧ず锛锛锛锛瑁瀹舵锛RND绫伙涓诲ㄥ娉电郴缁涓澶у舰瀵稿炽RND╁绯荤瀛ㄤ╁伴存ф涓濡缁垮澶ц甯绛锛跺绉╁伴虫ц涓藉凡涓у舰崇辩蹭缂╁绯荤锛濡榛茶¤绮绛姝ゅ褰缁跺ㄥ绉哄舵讹涓哄跺郊姝や骇稿浣ㄥ卞楂缁按骞炽╀富ㄥ娉电郴缁涓朵缁哄跺锋浣ㄦ楂缁按骞筹渚濡缁垮MexAB锛OprM涓跺灞ユ剧浣[11]褰澶绉涓诲ㄥ娉电郴缁跺琛ㄨ揪讹澶浣ㄥ寮[12]
锛涓锛姘ㄥ虹风被
姘ㄥ虹风被涓昏浣ㄤ姘ч╁伴存ц╁伴虫х锛瀵归剧寰寰澶╃舵皑虹风被富瑕╃ュ锛寰ц富瑕浜х璐ㄧ缂淇グ躲姝ゅ寰ц杩蹭寮寮璧风歌戒朵瑰绱ュ绛浜х
1ヨ╁锛绱ュ浼寮璧风瀵规姘ㄥ虹风被澶╃舵寰т按骞崇浜ゅ姘ㄥ虹风被绫诲瀛澶х澶╋瀹涓昏浣ㄤ璐ㄦ哥浣锛ㄤㄩ朵瑕缁缁澶锛╁伴存ц锛璐ㄨ锛╁伴存ц虫ц锛ㄩ╁伴存ц涓棣椤婚杩绂诲缁锛村涓寸瀛╄川锛澶绯澶藉涓ょ纾疯浜浠烽崇瀛Mg绂诲Ca绂诲澶绯纾疯缁蹇锛姘ㄥ虹风被涓崇瀛浠ｄ浠Ca绂诲锛浣挎绱绌块杩ヨ娴浜姘ㄥ虹风被ч浣灏辨涓轰浜绂诲杞Щ绯荤缂洪凤╂ュ锛濡剧浜绉缁
2姘ㄥ虹风淇グ讹姝ら舵杩璐ㄧ浠瀵肩遍╁伴存цㄥ虫ц浜х讹戒娇姘ㄥ虹风被绱澶辨椿锛宸茬ョ舵涓绫伙锛1锛涔拌浆绉婚讹AAC锛锛浣挎父绂荤轰板锛锛2锛歌疯浆绉婚讹ANT锛锛浣挎父绂荤烘歌峰锛锛3锛纾烽歌浆绉婚讹APH锛锛浣挎皑虹风被娓哥缇虹７稿朵腑锛纾烽歌浆绉婚跺绱ф楂涓绉跺浜х涓〃涓绉姘ㄥ虹风被╄借涓绉澶绉舵锛绉姘ㄥ虹风被╀借涓绉舵姝ゅㄤ姘ㄥ虹疯╅村ㄧ涓瀹ㄧ浜ゅс浜х剁璐ㄧ锛DNA娈碉锛杩瑰ㄧ缁磋浆绉伙浣垮ヤ缁浜хс
3歌戒朵淇グ锛ㄥぇK锛12腑锛变rpsl哄瑰锛浣挎歌戒S12藉瑰锛瀵归鹃绱浜х寰楂с歌戒剁淇グ瑰浜х瀵归鹃绱娣濂榛茶¤缁垮绮鹃绱缁稿涔变16SrRNA歌戒S12哄绐寮璧枫
锛锛澶х绱
ㄩ╁伴存ф涓缁澹澶瀵圭按ц╃娓т寸瀵瑰ぇ被绱绛绱烘锛寰ц瑙浜哥浣剁瑰绱椿
澶х被绱涓绱瀛涓锛浣浣ㄦ哄剁镐技锛瀹浠界50S歌戒浜轰锛惰介惧欢裤瀵硅浜绱父甯稿涓鸿寰erm哄锛绾㈤绱插哄讹锛erm哄缂浜х惰藉23SrRNA涓涓涓瑰ц哄ゆ6浣插哄瀵逛楠瀹ゅ绂诲虹澶ч插哄剁涓浠ョ猴杩浜朵慨楗颁浜rRNA淇轰腑绫荤被浼肩哄ゆ猴歌戒插哄瀵艰村澶х被绱浜ゅ涔芥插哄瑰浜哥浣璞★杩浣挎绱缁浣瑰浣绱浜插
瀵瑰ぇ被绱绱缁琛ㄨ揪缁瀵煎寤哄般惰〃杈剧被erm哄绉绫绘筹充插哄剁哄涓娓歌猴璋哄涓涓歌烽哥缃ゃ澶跺璇卞哄澶х被绱浜ゅ缁
榛茶¤璇卞т瀵瑰ぇ被涓孩绱哥孩绱姘孩绱瀵硅烘绱浜ゆ绱绛绱绫讳舵锛浜х瀵硅绫绘绱翠ф变孩绱哥孩绱姘孩绱芥璇卞插哄剁剧蜂杩璇卞缁寰
ㄦ浜¤涓瀵瑰ぇ被绱绫绘绱父辨哄甫ermC冲瀛缁灏川绮浠瀵笺よ虹剧澶锛涔ㄦ剧藉浜ц川绮锛ㄨ虹剧剧剧涓瀹璐ㄧDNA缂哄け寮璧疯х杞Щ
绱椿锛剁淇グ缁涓绱绱剁椿浠瀵艰村缁稿╃浠绾㈤绱ｈ韬绂诲板绾㈤绱楂搴锛杩浜杩浜х绾㈤绱舵杩2锛纾烽歌浆绉婚跺纾烽稿搴村ぇ被╃宸插ereAereB哄缂III锛ㄥ绾㈤绱楂搴涓父ereAereB澶╋缂rRNA插哄讹锛杩涔璇瀹浜涓ょ哄浜х╀寸浣ㄣ涓村涓瀵规绱楂搴变骇歌烽歌浆绉婚跺璧枫
绱娲绘ф车猴褰绾15锛锛20锛虹剧稿伴ч剧瀵瑰ぇ剁被╄惰哄朵剁椿浣ㄧ浜х绱娉靛虹郴缁mefEmefA冲瀛洪堕存ц¤瀵瑰ぇ被绱变骇ermC插哄讹浣涔稿伴涓鸿╃娲绘ф车鸿瀵艰磋榛茶¤ㄥ洪堕存ц¤涓msrA哄缂浜х涓绉锋杞界斤瀵艰村澶х被绱
剁缁瀵瑰绱涓哄瑙锛跺哄朵富瑕涓鸿寰澶婧DNA缂浜х绱娉靛虹郴缁锛锋歌戒淇やㄧ借川锛涔浠ュ涓烘蹭绐瀵艰村娓ч浣
1娓ф瑰锛澶ц甯涓蹭绐寮璧峰OmpF锛荤绱杩ヨ浣锛瀵艰村绱ㄥ绱瀛ㄤ浠ラ╁哄绱朵澶绉绱楂搴惰瀛ㄧ澶郴缁锛MAR锛锛marRAB绾靛锛OmpF澶芥伴杩涓绾靛涔琚绱讹mar绾靛婵娲讳瀵艰村绱娲绘ф车猴浣胯у锛ㄨ绉澶绉灞濡娌ㄨ灞蹇璐鸿灞蜂集灞告┘歌灞灞涓藉凡妫mar绯荤
2╂车猴浣缂浜х╂车虹郴缁村绱瑕哄讹杩涓杩绋辫Tet杩ヨ川瀛哄绱锛崇瀛澶╁杩DNA锛DNA浜わ浠复搴腑绂诲8绉缂娉靛虹郴缁哄锛tet锛A锛锛E锛哄ㄩ╁伴存ц涓箍娉妫娴猴ter锛P锛哄瀛ㄤ灞缁涓辩藉哄tetA锛P锛tetB 锛P锛澶哄缁锛tetA锛P锛缂涓车烘崇杞斤tetB锛P锛缂绫讳技tetM歌戒淇よ斤tet锛K锛tet锛L锛哄浠浜╁伴虫ц缁垮瀵瑰绱ㄥ璁稿绱烘舵哄舵芥ㄨ╂车虹郴缁
3歌戒淇や杩浣30S歌戒浜A浣瑰P浣瑰姘ㄥ洪tRNA浜插锛绱ュ舵浣ㄣ瀵瑰绱甯稿浜х涓绉借川锛杩绉借川歌戒镐浣浣胯借川涓绱褰卞锛绉版歌戒淇やㄣ歌戒淇やㄥtRNA淇グ荤锛蜂哄跺宸插绂诲5绉歌戒淇やㄥ哄锛tetMtetOtetPtetQtetSTetM甯涓哄箍娉锛ㄥ灞姘灞灞琛涓猴ㄦ浣插浣涓锛瀹村浣涓Tn916稿崇缁ц浆搴у涓ㄤ唤瑙浜蹭涓锛杩浜杞骇瀛杞Щэ瀹夸富村箍锛ㄥ绱瀛ㄦ惰浆绉婚澧锛绱浠ヨ澧寮哄惰〃杈撅tetOㄥ集茶灞剧灞灞涓猴tetPㄤ骇姘姊涓猴tetQㄧ被涓猴tetSㄤ骇哥╄绮涓
锛纾鸿哄叉哀у惰
1烘澶娓ч浣娇缁垮瀵圭叉哀у跺纾鸿鸿濂灞姊灞甯椴灞绫绘灞灞璇哄¤灞浠ョ叉哀у跺烘变绱缁DHFR浜插浣灞涔虫灞浜缁灞ュ荤己峰缁藉╃ㄥ婧у革琛ㄧ哄纾鸿哄叉哀у朵害锛涔╃ㄥ婧ц歌哄у讹涓稿寰躲
2瀵圭叉哀у惰寰ц锛1锛蹭绐锛ㄤ复搴涓甯稿瑙DHFR缁哄绐寮璧峰叉哀у惰濡澶ц甯虹剧娴琛绛锛ㄨ虹蜂集浜ф存涓蹭绐瀵艰寸澶娓т锛瀵硅堕搞叉哀у躲姘绱浜ゅ杩浜芥伴炽蹭绐椿歌烽稿讹瀵艰村纾鸿虹叉哀у跺骞堕搴杩浜绐瑕澶婧ц歌锋歌哄у跺DNA锛瀵瑰稿寰涓锛2锛璐ㄧ浠瀵艰瀵艰磋绉涓浜缁瀵圭叉哀у堕搴甯歌寰澶婧DNA浜х杩DHFR锛浜хDHFR琚叉哀у舵剁т蹭浠瀵肩躲ㄩ╁伴存ц锛灏ゅ舵ぇ甯涓杩ㄥ瀛涓绾хDNA锛DNA浜ゅ冲6绉涓DHFR锛告涔涓锛╁伴虫ц涓ゅ锛S1S2锛
DHFR涓甯骞挎DHFR I锛瀵艰村叉哀у堕搴剁稿哄dhfr I浣浜浆搴уTn7锛涓dhfr I哄浆ㄥ哄锛藉Tn7杞骇瀛澶妫猴dhfr II 瀵圭叉哀у舵ф浣dhfr㈠ㄤ激瀵娌ㄨ蹇璐鸿灞浜绉妫猴寮璧峰叉哀у惰dhfr ｅ借叉哀у惰瀵笺
ㄩ╁伴虫ц涓DHFR S1瀛ㄩ榛茶¤婧惰¤琛ㄧ¤浜哄¤涓藉凡妫虹dhfr A哄缂DHFR S1躲杩骞村ㄤ骇哥硅婧惰¤涓浜DHFR S2讹瀛ㄤ¤硅涓S1跺戒琛ㄧ哄绉诲ㄦу绐х瑰锛蹭浠瀵肩琛ㄧ¤朵凤涓轰姘ㄥ洪稿涓虹镐技
3瀵圭：鸿寰ц锛1锛蹭绐锛ㄥ灞缁榛茶¤涓蹭绐瀵艰PABA澧澶锛浜х瀵圭：鸿澶ц甯虹剧dhps哄绐筹绐dhps哄缂浜х瀵圭：轰翰DHPS锛2锛璐ㄧ浠瀵硷ㄤ缂浜хDHPS璐ㄧ瀵艰村纾鸿鸿寰цㄩ╁伴存ц涓凡绂诲哄sul I sul II哄缂DHPS III涔sul I哄朵哄歌锛浣浜卞ぇ缁璐ㄧ哄甫村瀛淇娈典锛sul II哄甯稿鹃绱哄歌锛瀛ㄤ涓昏村箍璐ㄧ灏缁ц川绮涓锛ㄤ复搴绂荤腑锛sul I sul II哄妫虹澶ц寸稿
锛涓锛硅被
1DNA烘跺村垛ｇ瑰锛ㄧ垮瑁涓DNA烘村垛ｆ甯搁瑕浣硅ㄤ朵璧峰版浣ㄣ惰缂烘跺村朵虹哄绐瀵艰村硅
涓村璇楠涔宸茶gyrA哄绐寮璧峰硅搴涔gyrA戒浜硅冲虹130bp搴涓ㄩ╁伴存у虫ц涓芥锛gyrB哄绐涔寮璧峰硅浣绋搴楂涓村ぇ澶扮gyrA绐寮璧凤涓瀛parC绐涔浼浣胯按骞冲寮猴浣剁浜gyrA涔
ㄩ╁伴虫ц濡榛茶¤虹剧绮涓瀵规硅gyrAparC哄绐寮璧枫告╁伴存ц瑷锛姘硅浣ㄤ╁伴虫ц村垛ｏㄥ涓娌榛茶¤虹剧涓parC绐浜gyrA杩涔绀洪╁伴淬虫хparC绐规
2澶娓ч浣╂车猴卞寮璧锋绱杩ヨ浣涓瀵艰村硅瀵瑰硅〃涓涓瑰锛杩涓澶mar浣圭炽ㄥ缁垮绌朵腑宸查村哄绉浣癸杩浜浣圭瑕瑰澶斤浠浣у磋ㄩ缁垮涓绂诲哄╂车鸿〃杈捐瀵瑰绉绱ㄩ榛茶¤涓浜娲绘ф车虹郴缁锛norA哄缂浜х锛璇ュ哄杩〃杈惧磋
1剁椿浣姘绱2涓猴琚隘绱杞板洪朵板锛ㄨ搴涓拌A涓轰板轰浣涔板浣ㄥC3缇猴褰㈡3锛涔版隘绱锛ㄤ跺涓3锛涔版隘绱杞褰㈡1锛涔版隘绱锛涔板涓1锛3浜涔版隘绱锛涓涔版隘绱浜涔版隘绱戒界50S歌戒浜轰杩瀵硅缁绐绌讹涓绐舵隘绱杞板洪剁芥辩稿浜虹涓绾х锛1锛╁伴虫ц涓姘绱杞板洪讹ㄩ榛茶¤涓杩垫吵宸插绂诲5绉涓姘绱杞板洪讹ABCD辫川绮PC194缂姘绱杞板洪躲缂剁缁哄甯镐浜疯璐ㄧ涓锛鸿〃杈惧辨隘绱璇卞锛瀵规隘绱绮虹剧浜х涓绉璇卞姘绱杞板洪讹浜ф姊2涓烘〃杈惧冲瀛锛catPcatQ锛2锛锛╁伴存ц涓隘绱杞板洪讹ㄩ╁伴存ц涓瀵规隘绱父辫川绮杞骇瀛哄璇卞锛杩浜哄甯歌瀹磋〃杈撅ㄨ缁涓宸查村轰3涓讹I°㈠锛锛I舵瀛界瑰х揣瀵缁绫诲洪绫绘绱锛缂姘绱杞板洪1哄甯镐浜Tn9杞骇瀛涓杩ユ轰缇ゅ哄锛界涔拌A版隘绱锛浣剁稿姘绱杞板洪朵锛绉颁负澶ヤ板鸿浆绉婚讹缁垮胯澹ゆ涓蹭缂躲ㄥぇ甯澶浆搴уTn2424涓涓姘绱冲瀛锛缂浜хXAT1Tn2424Tn21杩锛舵歌烽稿轰浜xat哄涓渚э绀烘哄村瀛涓ㄥ锛涓哄琛ㄨ揪ｆ炽
2娓ч浣蹭绐瀵艰村娓ч浣浼寮璧锋浜╁伴存ц瀵规隘绱濡ㄦ琛浼ゅ娌ㄨ涓瀵规隘绱楂搴富瑕涓芥伴瑰у界己澶辨筹缁垮涓cmlA哄浣垮ompAompC琛ㄨ揪锛浣胯琛浣姘绱
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