Identification of Potential Antimicrobial Targets of Pseudomonas aeruginosa Biofilms through a Novel Screening Approach.
Identification of Potential Antimicrobial Targets of Pseudomonas aeruginosa Biofilms through a Novel Screening Approach.
复制标题
通过一种新的筛选方法鉴定铜绿假单胞菌生物膜的潜在抗菌靶标。
DOI：
10.1128/spectrum.03099-22
复制
发表时间：
2023-02-13
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
铜绿假单胞菌是一种具有相当重要医学意义的机会性病原体，因为它对抗生素具有明显的耐受性，并与囊性纤维化和其他危及生命的疾病有关。本研究的目的是强调导致铜绿假单胞菌生物被膜对抗生素耐药的基因，从而确定潜在的新靶点，以开发抗生物被膜相关感染的药物。通过开发一种新的筛选方法和利用公共铜绿假单胞菌转座子插入文库，鉴定了几个与生物膜相关的基因。Pf噬菌体基因(PA0720)和鞭毛蛋白基因(Flc)赋予生物膜对庆大霉素的特异性耐受性。与参比生物膜相比，PA0720和flc突变株形成的生物膜被完全消除，庆大霉素浓度降低了4倍。此外，mreC、pprB、coxC和PA3785基因在提高生物膜对庆大霉素的耐受性方面发挥了重要作用。本研究对生物膜相关基因的分析为了解铜绿假单胞菌的耐药性提供了重要的新见解，这将有助于铜绿假单胞菌耐药性的检测和抗生物膜策略的制定。铜绿假单胞菌是一种具有重要医学意义的条件致病菌，是导致囊性纤维化患者死亡的主要病原体之一。除了遗传的抗生素耐药性外，铜绿假单胞菌还可以形成生物膜，生物膜的定义是嵌入到自我产生的细胞外聚合物基质中的微生物群落，这些基质相互黏附和/或附着在表面上。生物膜保护细菌免受抗生素治疗的影响，是治疗囊性纤维化引起的慢性感染时抗生素失败的主要原因。因此，至关重要的是制定新的治疗策略，以特别根除生物被膜。本研究的目的是推广一种新的生物被膜研究的筛选方法，并确定与铜绿假单胞菌生物被膜耐药相关的可能基因，以提高对生物被膜相关感染的认识，并为药物开发提供相关的治疗靶点。
Pseudomonas aeruginosa is an opportunistic pathogen of considerable medical importance, owing to its pronounced antibiotic tolerance and association with cystic fibrosis and other life-threatening diseases. The aim of this study was to highlight the genes responsible for P. aeruginosa biofilm tolerance to antibiotics and thereby identify potential new targets for the development of drugs against biofilm-related infections. By developing a novel screening approach and utilizing a public P. aeruginosa transposon insertion library, several biofilm-relevant genes were identified. The Pf phage gene (PA0720) and flagellin gene (fliC) conferred biofilm-specific tolerance to gentamicin. Compared with the reference biofilms, the biofilms formed by PA0720 and fliC mutants were completely eliminated with a 4-fold-lower gentamicin concentration. Furthermore, the mreC, pprB, coxC, and PA3785 genes were demonstrated to play major roles in enhancing biofilm tolerance to gentamicin. The analysis of biofilm-relevant genes performed in this study provides important novel insights into the understanding of P. aeruginosa antibiotic tolerance, which will facilitate the detection of antibiotic resistance and the development of antibiofilm strategies against P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogen of high medical importance and is one of the main pathogens responsible for the mortality of patients with cystic fibrosis. In addition to inherited antibiotic resistance, P. aeruginosa can form biofilms, defined as communities of microorganisms embedded in a self-produced matrix of extracellular polymeric substances adhering to each other and/or to a surface. Biofilms protect bacteria from antibiotic treatments and represent a major reason for antibiotic failure in the treatment of chronic infections caused by cystic fibrosis. Therefore, it is crucial to develop new therapeutic strategies aimed at specifically eradicating biofilms. The aim of this study was to generalize a novel screening method for biofilm research and to identify the possible genes involved in P. aeruginosa biofilm tolerance to antibiotics, both of which could improve the understanding of biofilm-related infections and allow for the identification of relevant therapeutic targets for drug development.
登录
查看更多内容
DOI：
10.1099/mic.0.2006/003533-0
发表时间：
2007-06
期刊：
Microbiology (Reading, England)
影响因子：
--
作者：
Mooij MJ;Drenkard E;Llamas MA;Vandenbroucke-Grauls CMJE;Savelkoul PHM;Ausubel FM;Bitter W
通讯作者：
Bitter W
影响因子：
30.3
作者：
Secor PR;Sweere JM;Michaels LA;Malkovskiy AV;Lazzareschi D;Katznelson E;Rajadas J;Birnbaum ME;Arrigoni A;Braun KR;Evanko SP;Stevens DA;Kaminsky W;Singh PK;Parks WC;Bollyky PL
通讯作者：
Bollyky PL
影响因子：
9.2
作者：
Varadarajan AR;Allan RN;Valentin JDP;Castañeda Ocampo OE;Somerville V;Pietsch F;Buhmann MT;West J;Skipp PJ;van der Mei HC;Ren Q;Schreiber F;Webb JS;Ahrens CH
通讯作者：
Ahrens CH
影响因子：
5.6
作者：
ALBERTS, B;FREY, L;DELIUS, H
通讯作者：
DELIUS, H
DOI：
10.1073/pnas.0307553101
发表时间：
2004-04-27
影响因子：
11.1
作者：
Wolfgang, MC;Jyot, J;Lory, S
通讯作者：
Lory, S