Composites of Bacterial Cellulose and Small Molecule-Decorated Gold Nanoparticles for Treating Gram-Negative Bacteria-Infected Wounds

Small ◽  
2017 ◽  
Vol 13 (27) ◽  
pp. 1700130 ◽  
Author(s):  
Ying Li ◽  
Yue Tian ◽  
Wenshu Zheng ◽  
Yan Feng ◽  
Rong Huang ◽  
...  
2010 ◽  
Vol 132 (35) ◽  
pp. 12349-12356 ◽  
Author(s):  
Yuyun Zhao ◽  
Yue Tian ◽  
Yan Cui ◽  
Wenwen Liu ◽  
Wanshun Ma ◽  
...  

2019 ◽  
Vol 116 (43) ◽  
pp. 21748-21757 ◽  
Author(s):  
Elizabeth M. Hart ◽  
Angela M. Mitchell ◽  
Anna Konovalova ◽  
Marcin Grabowicz ◽  
Jessica Sheng ◽  
...  

The development of new antimicrobial drugs is a priority to combat the increasing spread of multidrug-resistant bacteria. This development is especially problematic in gram-negative bacteria due to the outer membrane (OM) permeability barrier and multidrug efflux pumps. Therefore, we screened for compounds that target essential, nonredundant, surface-exposed processes in gram-negative bacteria. We identified a compound, MRL-494, that inhibits assembly of OM proteins (OMPs) by the β-barrel assembly machine (BAM complex). The BAM complex contains one essential surface-exposed protein, BamA. We constructed a bamA mutagenesis library, screened for resistance to MRL-494, and identified the mutation bamAE470K. BamAE470K restores OMP biogenesis in the presence of MRL-494. The mutant protein has both altered conformation and activity, suggesting it could either inhibit MRL-494 binding or allow BamA to function in the presence of MRL-494. By cellular thermal shift assay (CETSA), we determined that MRL-494 stabilizes BamA and BamAE470K from thermally induced aggregation, indicating direct or proximal binding to both BamA and BamAE470K. Thus, it is the altered activity of BamAE470K responsible for resistance to MRL-494. Strikingly, MRL-494 possesses a second mechanism of action that kills gram-positive organisms. In microbes lacking an OM, MRL-494 lethally disrupts the cytoplasmic membrane. We suggest that the compound cannot disrupt the cytoplasmic membrane of gram-negative bacteria because it cannot penetrate the OM. Instead, MRL-494 inhibits OMP biogenesis from outside the OM by targeting BamA. The identification of a small molecule that inhibits OMP biogenesis at the cell surface represents a distinct class of antibacterial agents.


2015 ◽  
Vol 62 (6) ◽  
pp. 521-527 ◽  
Author(s):  
Qun Ma ◽  
Nianchun Gong ◽  
Yanle Li ◽  
Xi Jiang ◽  
Li Yin ◽  
...  

2018 ◽  
Vol 2 (1) ◽  
pp. e201800242 ◽  
Author(s):  
Estelle Dumont ◽  
Julia Vergalli ◽  
Jelena Pajovic ◽  
Satya P Bhamidimarri ◽  
Koldo Morante ◽  
...  

Small molecule accumulation in Gram-negative bacteria is a key challenge to discover novel antibiotics, because of their two membranes and efflux pumps expelling toxic molecules. An approach to overcome this challenge is to hijack uptake pathways so that bacterial transporters shuttle the antibiotic to the cytoplasm. Here, we have characterized maltodextrin–fluorophore conjugates that can pass through both the outer and inner membranes mediated by components of theEscherichia colimaltose regulon. Single-channel electrophysiology recording demonstrated that the compounds permeate across the LamB channel leading to accumulation in the periplasm. We have also demonstrated that a maltotriose conjugate distributes into both the periplasm and cytoplasm. In the cytoplasm, the molecule activates the maltose regulon and triggers the expression of maltose binding protein in the periplasmic space indicating that the complete maltose entry pathway is induced. This maltotriose conjugate can (i) reach the periplasmic and cytoplasmic compartments to significant internal concentrations and (ii) auto-induce its own entry pathwayviathe activation of the maltose regulon, representing an interesting prototype to deliver molecules to the cytoplasm of Gram-negative bacteria.


2018 ◽  
Vol 18 (10) ◽  
pp. 834-843 ◽  
Author(s):  
Ping Wang ◽  
Jing Cheng ◽  
Cong-Cong Liu ◽  
Kai Tang ◽  
Feng Xu ◽  
...  

Metallo-β-lactamases (MBLs) are a family of Zn(II)-dependent enzymes that can hydrolyze almost all β-lactam antibiotics. Horizontal transfer of the genes encoding MBLs among Gram-negative bacteria pathogens has led to the emergence of extensively drug-resistant pathogens, which now represent a major threat to human health. As there is not to date yet a clinically available MBL inhibitor, the discovery of new MBL inhibitors has great urgency. This review highlights the recent developments in the discovery of small-molecule MBL inhibitors.


Author(s):  
Farooq Aziz ◽  
Muhammad Rashid ◽  
Mubashar Rehman ◽  
Muhammad Rafique ◽  
Muhammad Imran

Aims: The study aims to develop advanced antibacterial agents as nanoparticles instead of antibiotics due to the emergence of antimicrobial resistance. Background: Pseudomonas aeruginosa is capable of causing many diseases, including severe bacterial pneumonia. There is a need for an efficient antibacterial agent to kill these pathogens. Objective: The objective of the study is to synthesize advanced antibacterial agents as nanoparticles for biomedical applications that can play a vital role in killing Gram-negative bacteria (Pseudomonas aeruginosa). Method: A novel fabricated growth of hydrophilic spiky gold nanoparticles (SGNPs) via reduction method is reported. Results: The surface plasmon resonance peak of the synthesized SGNPs was tuned under the near-infrared range. The SGNPs have anisotropic and spiky morphology with 68 nm size and -58 mV surface charge. They are pure, possessing adsorption similar to the organic material. Pseudomonas aeruginosa treated with synthesized SGNPs showed 60% bacterial death at the concentration of 100 μM. Conclusion: This work consists of the novel synthesis of SGNPs via a safe and simple reduction method. The synthesized SGNPs exhibit strong antibacterial activity against the Gram-negative bacteria Pseudomonas aeruginosa measured using a microplate assay test. The result showed that these SGNPs are ideal for biomedical applications.


2014 ◽  
Vol 1051 ◽  
pp. 392-397
Author(s):  
T.V.M. Sreekanth ◽  
In Yong Eom

Gold nanoparticles (AuNPs) can be prepared in a number of chemical techniques, which are not environmentally friendly. Biosynthesis of nanoparticles by plant extracts is currently under exploitation. In this work, we describe an eco-friendly technique for green synthesis of AuNPs from AuCl4 solution using the Houttuynia cordata leaf extract as reducing agent. The AuNPs were characterized using UV-Visible spectroscopy, SEM, TEM, FTIR and AFM. The UV-Visible spectra indicate a strong plasma resonance that is located at 535 nm. The antibacterial activity of AuNPs was performed on various gram positive and gram negative bacteria. The AuNPs showed more inhibitory activity on gram negative than gram positive bacteria.


2012 ◽  
Vol 161 (1) ◽  
pp. 298-303 ◽  
Author(s):  
Haichao Su ◽  
Qiang Ma ◽  
Kun Shang ◽  
Tao Liu ◽  
Huanshun Yin ◽  
...  

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