scholarly journals Bacteriocins: An Overview of Antimicrobial, Toxicity, and Biosafety Assessment by in vivo Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Francisco Benítez-Chao ◽  
Angel León-Buitimea ◽  
Jordy Alexis Lerma-Escalera ◽  
José Rubén Morones-Ramírez
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Therapeutic Agents ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Infectious Agents ◽  
Key Factors ◽  
In Vivo Models ◽  
Drug Resistant Bacteria

The world is facing a significant increase in infections caused by drug-resistant infectious agents. In response, various strategies have been recently explored to treat them, including the development of bacteriocins. Bacteriocins are a group of antimicrobial peptides produced by bacteria, capable of controlling clinically relevant susceptible and drug-resistant bacteria. Bacteriocins have been studied to be able to modify and improve their physicochemical properties, pharmacological effects, and biosafety. This manuscript focuses on the research being developed on the biosafety of bacteriocins, which is a topic that has not been addressed extensively in previous reviews. This work discusses the studies that have tested the effect of bacteriocins against pathogens and assess their toxicity using in vivo models, including murine and other alternative animal models. Thus, this work concludes the urgency to increase and advance the in vivo models that both assess the efficacy of bacteriocins as antimicrobial agents and evaluate possible toxicity and side effects, which are key factors to determine their success as potential therapeutic agents in the fight against infections caused by multidrug-resistant microorganisms.

scholarly journals Current Mechanism of Bacterial Resistance to Antimicrobials

2018 ◽  
Vol 10 (01) ◽  
pp. 55-64
Author(s):  
Sonali Gangwar ◽  
Keerti Kaushik ◽  
Maya Datt Joshi
Keyword(s):  
Molecular Mechanisms ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Pathogenic Variants ◽  
Drug Resistant Bacteria

Serious infectious diseases are caused by bacterial pathogens that represents a serious public health concern. Antimicrobial agents are indicated for the treatment bacterial infections.Various bacteria carries several resistance genes also called multidrug resistant (MDR). Multidrug resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting the reservoirs of antibiotic resistant bacteria are present outside the hospital. Drug resistant bacteria that are selected with a single drug are also frequently multi-drug resistant against multiple structurally different drugs, thus confounding the chemotherapeutic efficacy of infectious disease caused by such pathogenic variants. The molecular mechanisms by which bacteria have common resistance to antibiotics are diverse and complex. This review highlights the mechanism of bacterial resistance to antimicrobials.

scholarly journals Histatin-Derived Monomeric and Dimeric Synthetic Peptides Show Strong Bactericidal Activity towards Multidrug-Resistant Staphylococcus aureus In Vivo

2007 ◽  
Vol 51 (9) ◽  
pp. 3416-3419 ◽  
Author(s):  
Mick M. Welling ◽  
Carlo P. J. M. Brouwer ◽  
Wim van ′t Hof ◽  
Enno C. I. Veerman ◽  
Arie V. Nieuw Amerongen
Keyword(s):  
Staphylococcus Aureus ◽  
Soft Tissue ◽  
Bactericidal Activity ◽  
Synthetic Peptides ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria

ABSTRACT Homodimerization of histatin-derived peptides generally led to improved bactericidal activity against Staphylococcus aureus in vitro. In vivo, monomers and dimers were equally active in killing bacteria in mice with a soft tissue infection. Altogether, these peptides are promising compounds for the development of novel therapeutics against infections with drug-resistant bacteria.

Current Mechanism of Bacterial Resistance to Antimicrobials

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Sonali Gangwar ◽  
Keerti Kaushik ◽  
Maya Datt Joshi
Keyword(s):  
Molecular Mechanisms ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Pathogenic Variants ◽  
Drug Resistant Bacteria

Serious infectious diseases are caused by bacterial pathogens that represents a serious public health concern. Antimicrobial agents are indicated for the treatment bacterial infections.Various bacteria carries several resistance genes also called multidrug resistant (MDR). Multidrug resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting the reservoirs of antibiotic resistant bacteria are present outside the hospital. Drug resistant bacteria that are selected with a single drug are also frequently multi-drug resistant against multiple structurally different drugs, thus confounding the chemotherapeutic efficacy of infectious disease caused by such pathogenic variants. The molecular mechanisms by which bacteria have common resistance to antibiotics are diverse and complex. This review highlights the mechanism of bacterial resistance to antimicrobials.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

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 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.

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