肽聚糖循环及细菌对β-内酰胺类抗生素的耐受性
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摘要
介绍肽聚糖循环及细菌对β-内酰胺类药物的耐药机制,为相关教学和科研工作提供参考。通过查阅文献,结合自身科研工作,对β-内酰胺类抗生素的抑菌机制和细菌对β-内酰胺类抗生素的耐药机制进行综述;β-内酰胺类抗生素可与转肽酶等蛋白质结合,破坏肽聚糖平衡,从而阻碍细胞正常生长;而细菌可通过β-内酰胺酶的诱导、外排泵的表达、外膜通透性增加和靶蛋白的修饰等措施来应对β-内酰胺类抗生素的作用,从而产生耐药。与肽聚糖循环有关的蛋白质,如转肽酶和转糖基酶,可作为β-内酰胺类新抗生素的筛选靶标;与细菌耐药性产生有关的蛋白质,如β-内酰胺酶,可作为β-内酰胺类抗生素辅助药物的筛选靶标。
To introduce peptidoglycan recycling and the β-lactams resistance mechanisms of bacteria,so that some help would be supplied to corresponding scientific workers and university teachers. By searching literatures,combined with our own studies,the bactericidal mechanisms of β-lactams and the resistance mechanisms of bacteria to β-lactams were summarized. The bactericidal activity ofβ-lactams is resulted from the inhibition of cell wall biosynthesis through combination with penicillin binding proteins such as transpeptidase destruction of peptidoglycan balances between biosynthesis and hydrolysis. The drug resistance of bacteria is resulted from the induction of β-lactamase,expression of out-pumping proteins,increase of outmembrane permeability,and modification of antibiotic target proteins. The proteins related to peptidoglycan recycling,such as transpeptidase and glycosyltransferase,would be potential targets for screening new β-lactams. The proteins related to β-lactams resistance,such as β-lactamase,would be potential targets for screening adjuvant drugs of β-lactams.
To introduce peptidoglycan recycling and the β-lactams resistance mechanisms of bacteria,so that some help would be supplied to corresponding scientific workers and university teachers. By searching literatures,combined with our own studies,the bactericidal mechanisms of β-lactams and the resistance mechanisms of bacteria to β-lactams were summarized. The bactericidal activity ofβ-lactams is resulted from the inhibition of cell wall biosynthesis through combination with penicillin binding proteins such as transpeptidase destruction of peptidoglycan balances between biosynthesis and hydrolysis. The drug resistance of bacteria is resulted from the induction of β-lactamase,expression of out-pumping proteins,increase of outmembrane permeability,and modification of antibiotic target proteins. The proteins related to peptidoglycan recycling,such as transpeptidase and glycosyltransferase,would be potential targets for screening new β-lactams. The proteins related to β-lactams resistance,such as β-lactamase,would be potential targets for screening adjuvant drugs of β-lactams.
引文
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[16]YIN J,SUN L,DONG Y,et al.Expression of bla A underlies unexpected ampicillin-induced cell lysis of Shewanella oneidensis[J].PLo S One,2013,8(3):e60460.
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[18]ZAMORANO L,MOYA B,JUAN C,et al.The Pseudomonas aeruginosa Cre BC two-component system plays a major role in the response toβ-lactams,fitness,biofilm growth,and global regulation[J].Antimicrob Agents Chemother,2014,58(9):5084-5095.
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[20]FISHER J F,MOBASHERY S.The sentinel role of peptidoglycan recycling in theβ-lactam resistance of the Gram-negative Enterobacteriaceae and Pseudomonas aeruginosa[J].Bioorg Chem,2014,56:41-48.
[21]ZHANG B,HU Y,ZHAO J,et al.Antimicrobial utilization and antimicrobial resistance trend before and after implementation of a3-year national antimicrobial steward ship program in a rertiary hospital[J].Chin Pharm J(中国药学杂志),2014,49(23):2136-2140.
[22]YUAN G J,LJ P B,CHEN S J,et al.Antimethicillin-resistant staphylococcus aureus activity of three main components of Azalomycin F[J].Chin Pharm J(中国药学杂志),2014,49(8):644-648.
[2]KOCAOGLU O,CARLSON E E.Profiling of beta-lactam selectivity for PBP in Escherichia coli strain DC2[J].Antimicrob Agents Chemother,2015,59(5):2785-2790.
[3]ZYKOV I N,SUNDSFJORD A,SMABREKKE L,et al.The antimicrobial activity of mecillinam,nitrofurantoin,temocillin and fosfomycin and comparative analysis of resistance patterns in a nationwide collection of ESBL producing Escherichia coli in Norway2010-2011[J].Infect Dis,2016,48(2):99-107.
[4]VOLLMER W,BLANOT D,DE PEDRO M A.Peptidoglycan structure and architecture[J].FEMS Microbiol Rev,2008,32(2):149-167.
[5]TYPAS A,BANZHAF M,VAN SAPAROEA B V D B,et al.Regulation of peptidoglycan synthesis by outer-membrane proteins[J].Cell,2010,143(7):1097-1109.
[6]SHAM L T,BUTLER E K,LEBAR M D,et al.Mur J is the flippase of lipid-linked precursors for peptidoglycan biogenesis[J].Science,2014,345(6193):220-222.
[7]LEE M,HESEK D,LLARRULL L I,et al.Reactions of all Escherichia coli lytic transglycosylases with bacterial cell wall[J].J Am Chem Soc,2013,135(135):3311-3314.
[8]SUN Y Y.Effects of lytic transglycosylases onβ-lactams resistance in Shewanella oneidensis[D].Hangzhou:Zhejiang University,2016.
[9]CHO H,UEHARA T,BERNHARDT T G.Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery[J].Cell,2014,159(6):1300-1311.
[10]YUNCK R,CHO H,BERNHARDT T G.Identification of Mlt G as a potential terminase for peptidoglycan polymerization in bacteria[J].Mol Microbiol,2015,104(4):523-530.
[11]YIN J,MAO Y,JU L,et al.Distinct roles of major peptidoglycan recycling enzymes inβ-lactamase production in Shewanella oneidensis[J].Antimicrob Agents Chemother,2014,58(11):6536-6543.
[12]JOHNSON J W,FISHER J F,MOBASHERY S.Bacterial cellwall recycling[J].Ann N Y Acad Sci,2013,1277(12):54-75.
[13]YIN J,SUN Y,MAO Y,et al.PBP1a/Lpo A but not PBP1b/Lpo B are involved in regulation of the majorβ-lactamase gene bla A in Shewanella oneidensis[J].Antimicrob Agents Chemother,2015,59(6):3357-3364.
[14]PARADIS-BLEAU C,MARKOVSKI M,UEHARA T,et al.Lipoprotein cofactors located in the outer membrane activate bacterial cell wall polymerases[J].Cell,2010,143(7):1110-1120.
[15]DRAWZ S M,BONOMO R A.Three decades ofβ-lactamase inhibitors[J].Clin Microbiol Rev,2010,23(1):160-201.
[16]YIN J,SUN L,DONG Y,et al.Expression of bla A underlies unexpected ampicillin-induced cell lysis of Shewanella oneidensis[J].PLo S One,2013,8(3):e60460.
[17]BALCEWICH M D,REEVE T M,ORLIKOW E A,et al.Crystal structure of the AmpR effector binding domain provides insight into the molecular regulation of inducible Amp Cβ-lactamase[J].J Mol Biol,2010,400(5):998-1010.
[18]ZAMORANO L,MOYA B,JUAN C,et al.The Pseudomonas aeruginosa Cre BC two-component system plays a major role in the response toβ-lactams,fitness,biofilm growth,and global regulation[J].Antimicrob Agents Chemother,2014,58(9):5084-5095.
[19]LAMERS R P,NGUYEN U T,NGUYEN Y,et al.Loss of membrane-bound lytic transglycosylases increases outer membrane permeability andβ-lactam sensitivity in Pseudomonas aeruginosa[J].Microbiology Open,2015,4(6):879-895.
[20]FISHER J F,MOBASHERY S.The sentinel role of peptidoglycan recycling in theβ-lactam resistance of the Gram-negative Enterobacteriaceae and Pseudomonas aeruginosa[J].Bioorg Chem,2014,56:41-48.
[21]ZHANG B,HU Y,ZHAO J,et al.Antimicrobial utilization and antimicrobial resistance trend before and after implementation of a3-year national antimicrobial steward ship program in a rertiary hospital[J].Chin Pharm J(中国药学杂志),2014,49(23):2136-2140.
[22]YUAN G J,LJ P B,CHEN S J,et al.Antimethicillin-resistant staphylococcus aureus activity of three main components of Azalomycin F[J].Chin Pharm J(中国药学杂志),2014,49(8):644-648.