scholarly journals Advances in Optical Detection of Human-Associated Pathogenic Bacteria

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5256
Author(s):  
Andrea Locke ◽  
Sean Fitzgerald ◽  
Anita Mahadevan-Jansen
Keyword(s):  
Pathogenic Bacteria ◽  
Optical Detection ◽  
Diagnostic Techniques ◽  
Laser Speckle ◽  
Resistant Bacteria ◽  
In Vivo Detection ◽  
Drug Resistant Bacteria ◽  
Detection And Identification ◽  
Free Environment

Bacterial infection is a global burden that results in numerous hospital visits and deaths annually. The rise of multi-drug resistant bacteria has dramatically increased this burden. Therefore, there is a clinical need to detect and identify bacteria rapidly and accurately in their native state or a culture-free environment. Current diagnostic techniques lack speed and effectiveness in detecting bacteria that are culture-negative, as well as options for in vivo detection. The optical detection of bacteria offers the potential to overcome these obstacles by providing various platforms that can detect bacteria rapidly, with minimum sample preparation, and, in some cases, culture-free directly from patient fluids or even in vivo. These modalities include infrared, Raman, and fluorescence spectroscopy, along with optical coherence tomography, interference, polarization, and laser speckle. However, these techniques are not without their own set of limitations. This review summarizes the strengths and weaknesses of utilizing each of these optical tools for rapid bacteria detection and identification.

scholarly journals Developing an antibiotic effective against multi-drug resistant bacteria.

2014 ◽  
Vol 70 (a1) ◽  
pp. C714-C714
Author(s):  
Calvin Steussy ◽  
Cynthia Stauffacher ◽  
Mark Lipton ◽  
Mohamed Seleem
Keyword(s):  
Pathogenic Bacteria ◽  
Modern Medicine ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Lead Compound ◽  
Drug Resistant Bacteria ◽  
Coa Reductase

The emergence of multi-drug resistant pathogenic bacteria is one of the great challenges to modern medicine. The gram positive cocci Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococcus faecalis (VRE) are two particularly virulent examples. In vivo studies have shown that the eukaryotic like 'mevalonate' isoprenoid pathway used by these pathogenic cocci is essential to their growth and virulence [1]. Our structures of HMG-CoA reductase (HMGR) from P. mevalonii demonstrated that the bacterial enzymes are structurally distinct from the human enzymes allowing for specific antibacterial activity [2]. High throughput in vitro screening against bacterial HMGR at the Southern Research Center, Birmingham, AL uncovered a lead compound with an IC50 of 80 µM with a competitive mode of action. Our x-ray crystal structures of HMGR from E. faecalis complexed with the lead compound and its variations have informed the synthesis of new inhibitors that have improved the IC50 to 5 µM [3]. Studies of this compound show it to be active against both MRSA and VRE in culture, effective against these bacteria in biofilms, and efficacious in a model system of eukaryotic infection. Structures and kinetics of these compounds will be presented and future directions discussed.

scholarly journals Resistance and Adaptation of Bacteria to Non-Antibiotic Antibacterial Agents: Physical Stressors, Nanoparticles, and Bacteriophages

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 435
Author(s):  
Sada Raza ◽  
Kinga Matuła ◽  
Sylwia Karoń ◽  
Jan Paczesny
Keyword(s):  
Antimicrobial Resistance ◽  
Antibacterial Agents ◽  
Uv Light ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Physical Factors ◽  
Defense Systems ◽  
Drug Resistant Bacteria

Antimicrobial resistance is a significant threat to human health worldwide, forcing scientists to explore non-traditional antibacterial agents to support rapid interventions and combat the emergence and spread of drug resistant bacteria. Many new antibiotic-free approaches are being developed while the old ones are being revised, resulting in creating unique solutions that arise at the interface of physics, nanotechnology, and microbiology. Specifically, physical factors (e.g., pressure, temperature, UV light) are increasingly used for industrial sterilization. Nanoparticles (unmodified or in combination with toxic compounds) are also applied to circumvent in vivo drug resistance mechanisms in bacteria. Recently, bacteriophage-based treatments are also gaining momentum due to their high bactericidal activity and specificity. Although the number of novel approaches for tackling the antimicrobial resistance crisis is snowballing, it is still unclear if any proposed solutions would provide a long-term remedy. This review aims to provide a detailed overview of how bacteria acquire resistance against these non-antibiotic factors. We also discuss innate bacterial defense systems and how bacteriophages have evolved to tackle them.

scholarly journals Screening of active antimicrobial and biological enzymes of microbial isolated from soil in Thailand

2017 ◽  
Vol 10 (4) ◽  
pp. 73 ◽  
Author(s):  
Pannapa Powthong ◽  
Apichai Sripean ◽  
Pattra Suntornthiticharoen
Keyword(s):  
Pathogenic Bacteria ◽  
Soil Microorganisms ◽  
Extracellular Enzyme ◽  
Antimicrobial Activities ◽  
Lipase Production ◽  
Resistant Bacteria ◽  
Strong Activity ◽  
Preliminary Screening ◽  
Soil Microbial ◽  
Drug Resistant Bacteria

Objective: The objectives of this study were to isolate microorganisms and screen for potential antimicrobial activities from the soil. Methods: In this study, a total of 425 isolates were isolated from 100 soil samples. The preliminary screening for antimicrobial activities of these isolates was performed by modified cross-streak, agar diffusion, and modified icrodilution technique against 16 pathogenic bacteria and fungi.Results: In the anti-microbial activity, there were three isolates, namely, 277, 303, and 307 exhibited inhibitory activity against methicillin-resistantStaphylococcus aureus and Salmonella typhimurium respectively. This study also examined the various enzymes producing from soil microorganisms including chitinase, chitosanase, amylase, cellulose, caseinase, gelatinase, esterase, and lipase production of different selective media for 24 and 48hrs using the direct spot method. The results revealed that 28 isolates could produce various enzymes with strong activity. Most of them produced gelatinase (5.65%) and caseinase (5.18%). There were four isolates that produce broad-spectrum enzyme. In addition, the investigation of selectedmicroorganism identification showed that they can be divided into three groups: Burkholderia spp., Pseudomonas spp., and Rhodococcus spp.Conclusion: This study demonstrated that the microorganisms from soil are capable of producing potential, antibacterial, and bioactive enzymes.Keywords: Antimicrobial activity, Extracellular enzyme, Soil microbial, Drug-resistant bacteria.

scholarly journals Quorum Sensing Inhibition in Chromobacterium violaceum, Antibacterial Activity and GC-MS Analysis of Centaurea praecox (Oliv. & Hiern) Extracts

2020 ◽  
Vol 9 (4) ◽  
pp. 1569-1577
Keyword(s):  
Antibacterial Activity ◽  
Quorum Sensing ◽  
Research Strategy ◽  
Chromobacterium Violaceum ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Control Drug ◽  
Ms Analysis ◽  
Drug Resistant Bacteria

The quorum sensing (QS) mechanism has become a viable research strategy for the discovery of plant-derived anti-virulent agents to control drug-resistant bacteria. The increasing incidences of drug-resistant bacteria and the effort to curb it necessitate this study. We investigated the QS inhibitory potential of Centaurea praecox extracts on Chromobacterium violaceum (CV), antibacterial activity, and determination of chemical composition using GC-MS. C. praecox was subjected to sequential extraction using hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), ethanol (ET), and aqueous (AQ) solvents. The extracts were subsequently evaluated for antibacterial activity using disc diffusion and QS violacein inhibition using spectrophotometry. The antibacterial effects of the extracts were moderate on gram-positive bacteria at 4 mg/mL in the order: HEX >EA >DCM >ET =AQ. However, the DCM extract demonstrated the most effective violacein inhibition of ≥80% at 0.3 mg/mL. QS violacein inhibitions were generally found to be concentration-dependent in the order: DCM >EA >HEX >ET =AQ with efficacies of ≥ 90% inhibition at ≥ 0.6 mg/mL. GC-MS analysis on the most potent DCM extract revealed N-vinylmethanimine, N-ethyl formamide, and propanamide among components identified. We concluded that C. praecox DCM extract contains bioactive chemicals as QS inhibitors and potential anti-virulent agents capable of combating the pathogenicity of drug-resistant bacteria in vivo.

scholarly journals Reversion of antibiotic resistance in drug-resistant bacteria using non-steroidal anti-inflammatory drug benzydamine

2021 ◽  
Author(s):  
Yuan Liu ◽  
Ziwen Tong ◽  
Jingru Shi ◽  
Tian Deng ◽  
Ruichao Li ◽  
...  
Keyword(s):  
Cost Effective ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Inflammatory Drug ◽  
Development Of Resistance ◽  
Drug Resistant Bacteria ◽  
Metabolic States ◽  
Anti Inflammatory ◽  
Approved Drugs

Antimicrobial resistance has been a growing concern that gradually undermines our tradition treatment regimen. The fact that few antibacterial drugs with new scaffolds or targets have been approved in the past two decades aggravates this crisis. Repurposing previously approved drugs as potent antibiotic adjuvants offers a cost effective strategy to mitigate the development of resistance and tackle the increasing infections by multidrug resistant (MDR) bacteria. Herein, we found that benzydamine, a widely used non-steroidal anti-inflammatory drug in clinic, remarkably potentiated broad spectrum antibiotic tetracyclines activity against a panel of clinical important resistant pathogens, including MRSA, VRE, MCRPEC and tet (X)-positive Gram negative bacteria. Further mechanistically experiments showed that benzydamine dissipated membrane potential (ΔΨ) in both Gram positive and negative bacteria, which in turn upregulated the transmembrane proton gradient (ΔpH) and promoted the uptake of tetracyclines. Additionally, benzydamine exacerbated the oxidative stress by triggering the production of ROS and suppressing GAD system mediated oxidative defensive. This mode of action explains the great bactericidal activity of the doxycycline benzydamine combination against different metabolic states of bacteria including persister cells. As a proof of concept, the in vivo efficacy of this combination therapy was evidenced in multiple animal infection models. These findings revealed that benzydamine is a promising tetracycline antibiotics adjuvant and has the potential to address life threatening infections by MDR bacteria.

scholarly journals Nanoparticles Enable Efficient Delivery of Antimicrobial Peptides for the Treatment of Deep Infections

2021 ◽  
Author(s):  
Yingxue Deng ◽  
Rui Huang ◽  
Songyin Huang ◽  
Menghua Xiong
Keyword(s):  
Antimicrobial Peptides ◽  
Broad Spectrum ◽  
Antimicrobial Properties ◽  
Therapeutic Index ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Efficient Delivery ◽  
Delivery Vehicles

Antimicrobial peptides (AMPs) have emerged as promising alternatives of traditional antibiotics against drug-resistant bacteria owing to their broad-spectrum antimicrobial properties and low tendency to drugresistance. However, their therapeutic efficacy in vivo, especially for infections in deep organs, is limited owing to their systemic toxicity and low bioavailability. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Herein, we will discuss the current progress of using nanoparticles as delivery vehicles for AMPs for the treatment of deep infections.

scholarly journals Targeted-Antibacterial-Plasmids (TAPs) combining conjugation and CRISPR/Cas systems achieve strain-specific antibacterial activity

2020 ◽  
Author(s):  
Audrey Reuter ◽  
Cécile Hilpert ◽  
Annick Dedieu-Berne ◽  
Sophie Lematre ◽  
Erwan Gueguen ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Carbapenem Resistance ◽  
Double Strand Breaks ◽  
Resistant Bacteria ◽  
Innovative Strategy ◽  
Strand Breaks ◽  
Drug Resistant Bacteria

AbstractThe global emergence of drug-resistant bacteria leads to the loss of efficacy of our antibiotics arsenal and severely limits the success of currently available treatments. Here, we developed an innovative strategy based on Targeted-Antibacterial-Plasmids (TAPs) that use bacterial conjugation to deliver CRISPR/Cas systems exerting a strain-specific antibacterial activity. TAPs are highly versatile as they can be directed against any specific genomic or plasmid DNA using the custom algorithm (CSTB) that identifies appropriate targeting spacer sequences. We demonstrate the ability of TAPs to induce strain-selective killing by introducing lethal double strand breaks (DSBs) into the targeted genomes. TAPs directed against a plasmid-born carbapenem resistance gene efficiently resensitise the strain to the drug. This work represents an essential step towards the development of an alternative to antibiotic treatments, which could be used for in situ microbiota modification to eradicate targeted resistant and/or pathogenic bacteria without affecting other non-targeted bacterial species.

scholarly journals Design, Engineering and Discovery of Novel α-Helical and β-Boomerang Antimicrobial Peptides against Drug Resistant Bacteria

2020 ◽  
Vol 21 (16) ◽  
pp. 5773 ◽  
Author(s):  
Surajit Bhattacharjya ◽  
Suzana K. Straus
Keyword(s):  
Antimicrobial Peptides ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Development ◽  
Extensively Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Drying Up ◽  
Further Development ◽  
Lps Binding

In an era where the pipeline of new antibiotic development is drying up, the continuous rise of multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria are genuine threats to human health. Although antimicrobial peptides (AMPs) may serve as promising leads against drug resistant bacteria, only a few AMPs are in advanced clinical trials. The limitations of AMPs, namely their low in vivo activity, toxicity, and poor bioavailability, need to be addressed. Here, we review engineering of frog derived short α-helical AMPs (aurein, temporins) and lipopolysaccharide (LPS) binding designed β-boomerang AMPs for further development. The discovery of novel cell selective AMPs from the human proprotein convertase furin is also discussed.

scholarly journals Thermo-responsive triple-function nanotransporter for efficient chemo-photothermal therapy of multidrug-resistant bacterial infection

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Guangchao Qing ◽  
Xianxian Zhao ◽  
Ningqiang Gong ◽  
Jing Chen ◽  
Xianlei Li ◽  
...  
Keyword(s):  
Near Infrared ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Limited Effect ◽  
Bacterial Membranes ◽  
Change Mechanism ◽  
Drug Resistant Bacteria ◽  
New Strategies

Abstract New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus, whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria.

Pharmacotherapy of Complicated Urinary Tract and Intra-abdominal Infections with Doripenem

2009 ◽  
Vol 1 ◽  
pp. CMT.S2062
Author(s):  
Anthony M. Nicasio ◽  
Joseph L. Kuti ◽  
David P. Nicolau
Keyword(s):  
Urinary Tract ◽  
Broad Spectrum ◽  
Drug Dose ◽  
Resistant Bacteria ◽  
Drug Resistant Bacteria ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections ◽  
Abdominal Infections

Due to the growing rate of multi-drug resistant bacteria in complicated infections, the need for new broad-spectrum antimicrobials is paramount. Doripenem, a new addition to the intravenous carbapenem class, has recently been approved for the treatment of complicated lower urinary tract infections and/or pyelonephritis (cUTI) and complicated intra-abdominal infections (cIAI) in adult patients. Doripenem exhibits potent in vitro and in vivo bactericidal activity against an assortment of Gram-positive and Gram-negative aerobic and anaerobic organisms, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae that produce extended spectrum beta-lactamases (ESBL). Relative to other available carbapenems, doripenem typically displays MICs that are 1-2 dilutions lower than meropenem and 2-4 dilutions lower than imipenem against P. aeruginosa. Since the kidneys primarily excrete doripenem as whole drug, dose adjustments are needed in patients with renal impairment. Doripenem 500 mg q8 h demonstrated non-inferiority to levofloxacin 250 mg q24 h in clinical trials of patients with cUTI; it was non-inferior to meropenem 1000 mg q8 h in patients with cIAI. Doripenem's broad spectrum of activity, in vitro potency against particularly difficult to treat organisms, and desirable safety profile make it an attractive option in the treatment of cUTI and cIAI.

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