scholarly journals Antimicrobial Peptides: Virulence and Resistance Modulation in Gram-Negative Bacteria

2020 ◽  
Vol 8 (2) ◽  
pp. 280 ◽  
Author(s):  
Marylise Duperthuy
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Low Concentrations ◽  
Resistance Modulation ◽  
Subinhibitory Concentrations ◽  
The Impact

Growing resistance to antibiotics is one of the biggest threats to human health. One of the possibilities to overcome this resistance is to use and develop alternative molecules such as antimicrobial peptides (AMPs). However, an increasing number of studies have shown that bacterial resistance to AMPs does exist. Since AMPs are immunity molecules, it is important to ensure that their potential therapeutic use is not harmful in the long term. Recently, several studies have focused on the adaptation of Gram-negative bacteria to subinhibitory concentrations of AMPs. Such concentrations are commonly found in vivo and in the environment. It is therefore necessary to understand how bacteria detect and respond to low concentrations of AMPs. This review focuses on recent findings regarding the impact of subinhibitory concentrations of AMPs on the modulation of virulence and resistance in Gram-negative bacteria.

scholarly journals Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Mark Austin Hanson ◽  
Anna Dostálová ◽  
Camilla Ceroni ◽  
Mickael Poidevin ◽  
Shu Kondo ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Fungal Pathogens ◽  
Gene Editing ◽  
Cationic Peptides ◽  
Gram Negative Bacteria ◽  
Biological Processes ◽  
Gram Negative ◽  
Bacteria And Fungi

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilized CRISPR gene editing to delete most known immune-inducible AMPs of Drosophila, namely: 4 Attacins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking these ten AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, contributing either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.

scholarly journals Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging

2021 ◽  
Vol 12 ◽  
Author(s):  
Ni Zhang ◽  
Lichong Zhu ◽  
Qiuhong Ouyang ◽  
Saisai Yue ◽  
Yichun Huang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Polymyxin B ◽  
Susceptibility Weighted Imaging ◽  
Gram Negative Bacteria ◽  
Severe Toxicity ◽  
Gram Negative ◽  
The Impact

Polymyxin B (PMB) exert bactericidal effects on the cell wall of Gram-negative bacteria, leading to changes in the permeability of the cytoplasmic membrane and resulting in cell death, which is sensitive to the multi-resistant Gram-negative bacteria. However, the severe toxicity and adverse side effects largely hamper the clinical application of PMB. Although the molecular pathology of PMB neurotoxicity has been adequately studied at the cellular and molecular level. However, the impact of PMB on the physiological states of central nervous system in vivo may be quite different from that in vitro, which need to be further studied. Therefore, in the current study, the biocompatible ultra-uniform Fe3O4 nanoparticles were employed for noninvasively in vivo visualizing the potential impairment of PMB to the central nervous system. Systematic studies clearly reveal that the prepared Fe3O4 nanoparticles can serve as an appropriate magnetic resonance contrast agent with high transverse relaxivity and outstanding biosafety, which thus enables the following in vivo susceptibility-weighted imaging (SWI) studies on the PMB-treated mice models. As a result, it is first found that the blood-brain barrier (BBB) of mice may be impaired by successive PMB administration, displaying by the discrete punctate SWI signals distributed asymmetrically across brain regions in brain parenchyma. This result may pave a noninvasive approach for in-depth studies of PMB medication strategy, monitoring the BBB changes during PMB treatment, and even assessing the risk after PMB successive medication in multidrug-resistant Gram-negative bacterial infected patients from the perspective of medical imaging.

scholarly journals In vivo studies on antibiotic combination for the treatment of carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis protocol

2020 ◽  
Vol 4 (1) ◽  
pp. e100055
Author(s):  
Elda Righi ◽  
Luigia Scudeller ◽  
Margherita Chiamenti ◽  
Kamilia Abdelraouf ◽  
Thomas Lodise ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
In Vivo Models ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
The Impact ◽  
Antibiotic Combination

ObjectiveThere is poor evidence to determine the superiority of combination regimens versus monotherapy against infections due to carbapenem-resistant (CR) Gram-negative bacteria. In vivo models can simulate the pathophysiology of infections in humans and assess antibiotic efficacy. We aim to investigate in vivo effects of antibiotic combination on mortality and disease burden for infections due to CR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae and provide an unbiased overview of existing knowledge. The results of the study can help prioritising future research on the most promising therapies against CR bacteria.Methods and analysisThis protocol was formulated using the Systematic Review Protocol for Animal Intervention Studies (SYRCLE) Checklist. Publications will be collected from PubMed, Scopus, Embase and Web of Science. Quality checklists adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and SYRCLE’s risk of bias tool will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by I2 test. Subgroup meta-analysis will be performed when possible to assess the impact of the studies on efficacy of the treatments. Funnel plotting will be used to evaluate the risk of publication bias.DisseminationThis systematic review and meta-analysis is part of a wider research collaboration project, the COmbination tHErapy to treat sepsis due to carbapenem-Resistant bacteria in adult and paediatric population: EvideNCE and common practice (COHERENCE) study that includes also the analyses of in vitro and human studies. Data will be presented at international conferences and the results will be published in peer-reviewed journals.PROSPERO registration numberCRD42019128104(available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128104).

scholarly journals Multiple Mechanisms of the Synthesized Antimicrobial Peptide TS against Gram-Negative Bacteria for High Efficacy Antibacterial Action In Vivo

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 60
Author(s):  
Rui Zhang ◽  
Xiaobo Fan ◽  
Xinglu Jiang ◽  
Mingyuan Zou ◽  
Han Xiao ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Divalent Cations ◽  
Resistant Bacteria ◽  
Antibacterial Drug ◽  
Gram Negative Bacteria ◽  
Gram Negative

The emergence of drug-resistant bacteria emphasizes the urgent need for novel antibiotics. The antimicrobial peptide TS shows extensive antibacterial activity in vitro and in vivo, especially in gram-negative bacteria; however, its antibacterial mechanism is unclear. Here, we find that TS without hemolytic activity disrupts the integrity of the outer bacterial cell membrane by displacing divalent cations and competitively binding lipopolysaccharides. In addition, the antimicrobial peptide TS can inhibit and kill E. coli by disintegrating the bacteria from within by interacting with bacterial DNA. Thus, antimicrobial peptide TS’s multiple antibacterial mechanisms may not easily induce bacterial resistance, suggesting use as an antibacterial drug to be for combating bacterial infections in the future.

scholarly journals Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach

2018 ◽  
Author(s):  
Mark Austin Hanson ◽  
Anna Dostalova ◽  
Camilla Ceroni ◽  
Mickael Poidevin ◽  
Shu Kondo ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Fungal Pathogens ◽  
Gene Editing ◽  
Cationic Peptides ◽  
Gram Negative Bacteria ◽  
Biological Processes ◽  
Gram Negative ◽  
Bacteria And Fungi

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilised CRISPR gene editing to delete all known immune inducible AMPs of Drosophila, namely: 4 Attacins, 4 Cecropins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking all 14 AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, acting either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.

scholarly journals Integrated endotoxin-adsorption and antibacterial properties of platelet-membrane-coated copper silicate hollow microspheres for wound healing

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zaihui Peng ◽  
Xiaochun Zhang ◽  
Long Yuan ◽  
Ting Li ◽  
Yajie Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Bacterial Infections ◽  
Antibacterial Properties ◽  
Platelet Membrane ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
The Impact ◽  
Copper Silicate

AbstractSerious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bacter icidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents. Graphical Abstract

scholarly journals Antimicrobial Peptide Resistance Genes in the Plant Pathogen Dickeya dadantii

2016 ◽  
Vol 82 (21) ◽  
pp. 6423-6430 ◽  
Author(s):  
Caroline Pandin ◽  
Martine Caroff ◽  
Guy Condemine
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Soft Rot ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Dickeya Dadantii ◽  
Gram Negative ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
New Genes

ABSTRACTModification of teichoic acid through the incorporation ofd-alanine confers resistance in Gram-positive bacteria to antimicrobial peptides (AMPs). This process involves the products of thedltXABCDgenes. These genes are widespread in Gram-positive bacteria, and they are also found in a few Gram-negative bacteria. Notably, these genes are present in all soft-rot enterobacteria (PectobacteriumandDickeya) whosedltDXBACoperons have been sequenced. We studied the function and regulation of these genes inDickeya dadantii.dltBexpression was induced in the presence of the AMP polymyxin. It was not regulated by PhoP, which controls the expression of some genes involved in AMP resistance, but was regulated by ArcA, which has been identified as an activator of genes involved in AMP resistance. However,arcAwas not the regulator responsible for polymyxin induction of these genes in this bacterium, which underlines the complexity of the mechanisms controlling AMP resistance inD. dadantii. Two other genes involved in resistance to AMPs have also been characterized,phoSandphoH.dltB,phoS,phoH, andarcAbut notdltDmutants were more sensitive to polymyxin than the wild-type strain. Decreased fitness of thedltB,phoS, andphoHmutants in chicory leaves indicates that their products are important for resistance to plant AMPs.IMPORTANCEGram-negative bacteria can modify their lipopolysaccharides (LPSs) to resist antimicrobial peptides (AMPs). Soft-rot enterobacteria (DickeyaandPectobacteriumspp.) possess homologues of thedltgenes in their genomes which, in Gram-positive bacteria, are involved in resistance to AMPs. In this study, we show that these genes confer resistance to AMPs, probably by modifying LPSs, and that they are required for the fitness of the bacteria during plant infection. Two other new genes involved in resistance were also analyzed. These results show that bacterial resistance to AMPs can occur in bacteria through many different mechanisms that need to be characterized.

Relationship between Adaptive Changing of Lysophosphatidylethanolamine Content in the Bacterial Envelope and Ampicillin Sensitivity of Yersinia pseudotuberculosis

2018 ◽  
Vol 28 (5) ◽  
pp. 236-239
Author(s):  
Nina Sanina ◽  
Lyudmila Pomazenkova ◽  
Svetlana Bakholdina ◽  
Natalia Chopenko ◽  
Anna Zabolotnaya ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Culture Medium ◽  
Bacterial Resistance ◽  
Yersinia Pseudotuberculosis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Control Value ◽  
And Function

The low permeability of porin channels is the possible reason for Gram-negative bacterial resistance to antibiotics. The adaptive accumulation of lysophosphatidylethanolamine (LPE) in <i>Yersinia pseudotuberculosis</i> induces conformational changes of OmpF porin that may hinder the transport of antibiotics through this channel. The present study was aimed to test whether the changes in LPE content affect the resistance of bacteria to ampicillin. The addition of glucose to the culture medium was shown to simultaneously increase the level of LPE and minimum inhibitory concentration (MIC) for ampicillin of <i>Y. pseudotuberculosis</i> cells 6- and 2-fold, respectively. However, the coadministration of glucose and polyphenol extract from buckwheat husks reduced the content of LPE 2-fold and restored MIC to the control value. Thus, PBEH can be used as antibiotic adjuvant to improve an antibiotic’s ability to cross the outer membrane. The present work demonstrated: (i) the role of adaptive changes in the lipid composition of <i>Y. pseudotuberculosis</i> in<i></i> the development of antibiotic resistance, and (ii) the promising use of PBEH in combination therapy to increase the susceptibility of Gram-negative bacteria to the conventional β-lactam antibiotics, probably attenuating in vivo a previously demonstrated effect of LPE on the conformation and function of the OmpF channel.

scholarly journals Antibiogram for Haemodialysis Catheter-Related Bloodstream Infections

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Abdul Halim Abdul Gafor ◽  
Pau Cheong Ping ◽  
Anis Farahanum Zainal Abidin ◽  
Muhammad Zulhilmie Saruddin ◽  
Ng Kah Yan ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Major Complication ◽  
Bloodstream Infections ◽  
Coagulase Negative Staphylococcus ◽  
Gram Negative Bacteria ◽  
Sensitivity Testing ◽  
Gram Positive ◽  
Gram Negative ◽  
Empirical Antibiotics

Background. Haemodialysis (HD) catheter-related bloodstream infections (CRBSIs) are a major complication of long-term catheter use in HD. This study identified the epidemiology of HD CRBSIs and to aid in the choice of empiric antibiotics therapy given to patients with HD CRBSIs.Methods. Patients with HD CRBSIs were identified. Their blood cultures were performed according to standard sterile technique. Specimens were sent to the microbiology lab for culture and sensitivity testing. Results were tabulated in antibiograms.Results. 18 patients with a median age of 61.0 years (IQR: 51.5–73.25) were confirmed to have HD CRBSIs based on our study criteria. Eight (44.4%) patients had gram-negative infections, 7 (38.9%) patients gram-positive infections, and 3 (16.7%) patients had polymicrobial infections. We noted that most of the gram-negative bacteria were sensitive to ceftazidime. Unfortunately, cloxacillin resistance was high among gram-positive organisms.Coagulase-negative StaphylococcusandBacillussp. were the most common gram-positive organisms and they were sensitive to vancomycin.Conclusion. Our study revealed the increased incidence of gram-negative organism in HD CRBSIs. Antibiogram is an important tool in deciding empirical antibiotics for HD CRBSIs. Tailoring your antibiotics accordingly to the antibiogram can increase the chance of successful treatment and prevent the emergence of bacterial resistance.

scholarly journals Integrated Endotoxin-Adsorption and Antibacterial Properties of Platelet-Membrane-Coated Copper Silicate Hollow Microspheres for Wound Healing

2021 ◽  
Author(s):  
Zaihui Peng ◽  
Xiaochun Zhang ◽  
Long Yuan ◽  
Yajie Chen ◽  
Ting Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Bacterial Infections ◽  
Antibacterial Properties ◽  
Platelet Membrane ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
The Impact ◽  
Copper Silicate

Abstract Serious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bactericidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents.

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