| 1 | Pseudomonas aeruginosa:pathogenesis,virulence factors,antibiotic resistance,interaction with host,technology advances and emerging therapeutics显示文摘Pseudomonas aeruginosa(P.aeruginosa)is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis,burn wounds,immunodeficiency,chronic obstructive pulmonary disorder(COPD),cancer,and severe infection requiring ventilation,such as COVID-19.P.aeruginosa is also a widely-used model bacterium for all biological areas.In addition to continued,intense efforts in understanding bacterial pathogenesis of P.aeruginosa including virulence factors(LPS,quorum sensing,two-component systems,6 type secretion systems,outer membrane vesicles(OMVs),CRISPR-Cas and their regulation),rapid progress has been made in further studying host-pathogen interaction,particularly host immune networks involving autophagy,inflammasome,noncoding RNAs,cGAS,etc.Furthermore,numerous technologic advances,such as bioinformatics,metabolomics,scRNA-seq,nanoparticles,drug screening,and phage therapy,have been used to improve our understanding of P.aeruginosa pathogenesis and host defense.Nevertheless,much remains to be uncovered about interactions between P.aeruginosa and host immune responses,including mechanisms of drug resistance by known or unannotated bacterial virulence factors as well as mammalian cell signaling pathways.The widespread use of antibiotics and the slow development of effective antimicrobials present daunting challenges and necessitate new theoretical and practical platforms to screen and develop mechanism-tested novel drugs to treat intractable infections,especially those caused by multi-drug resistance strains.Benefited from has advancing in research tools and technology,dissecting this pathogen’s feature has entered into molecular and mechanistic details as well as dynamic and holistic views.Herein,we comprehensively review the progress and discuss the current status of P.aeruginosa biophysical traits,behaviors,virulence factors,invasive regulators,and host defense patterns against its infection,which point out new directions for future investigation and add to the design of novel and/or alternative therapeutics to combat this clinically significant pathogen. | Shugang Qin Wen Xiao Chuanmin Zhou Qinqin Pu Xin Deng Lefu Lan Haihua Liang Xiangrong Song Min Wu | 2022 | Signal Transduction and Targeted Therapy2022，7，7： | 5 |
| 6 | Discovery of synergistic activity of fluoroquinolones in combination with antimicrobial peptides against clinical polymyxin-resistant Pseudomonas aeruginosa DK2显示文摘Polymyxin B(PB),as the last-line of defense against multidrug-resistant Gram-negative bacteria,has caused resistance to P.aeruginosa recently.Fortunately,synergistic treatment could preserve the last class of antibiotics and reduce the emergency of drug resistance.Here,we performed a screen of 970 approved drugs synergized with PB against the P.aeruginosa DK2,which is severely resistant to PB,MIC=512μg/mL.Encouragingly,we found fluoroquinolones could synergy with PB and achieved an obvious reduction in MIC of PB below the clinical susceptible breakpoint(2 μg/mL).Especially,gemifloxacin achieved the highest synergistic effect with PB,leading to a 4096-fold MIC reduction(reduced from512 μg/mL to 0.125 μg/mL).Furthermore,synergistic effect was also observed in the combination of gemifloxacin and colistin.Finally,outer membrane permeabilization assay showed that gemifloxacin could increase the permeability of bacterial cell membranes for P.aeruginosa which partly explained the synergy mechanism.These results indicate that fluoroquinolones represent attractive synergists to address the emerging threat of polymyxin-resistant infections. | Xinyu Zheng Qiao Cao Qin Cao Fei Mao Xiaokang Li Jin Zhu Lefu Lan Jian Li | 2020 | Chinese Chemical Letters2020，31，2： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员