scholarly journals Antibiofilm Peptides: Potential as Broad-Spectrum Agents

2016 ◽  
Vol 198 (19) ◽  
pp. 2572-2578 ◽  
Author(s):  
Daniel Pletzer ◽  
Robert E. W. Hancock
Keyword(s):  
Broad Spectrum ◽  
Bacterial Species ◽  
Antibiofilm Activity ◽  
Promising Alternative ◽  
Content Type ◽  
Bacterial Diseases ◽  
Novel Approach ◽  
Recent Developments ◽  
Biofilm Bacteria ◽  
Conventional Antibiotics

The treatment of bacterial diseases is facing twin threats, with increasing bacterial antibiotic resistance and relatively few novel compounds or strategies under development or entering the clinic. Bacteria frequently grow on surfaces as biofilm communities encased in a polymeric matrix. The biofilm mode of growth is associated with 65 to 80% of all clinical infections. It causes broad adaptive changes; biofilm bacteria are especially (10- to 1,000-fold) resistant to conventional antibiotics and to date no antimicrobials have been developed specifically to treat biofilms. Small synthetic peptides with broad-spectrum antibiofilm activity represent a novel approach to treat biofilm-related infections. Recent developments have provided evidence that these peptides can inhibit even developed biofilms, kill multiple bacterial species in biofilms (including the ESKAPE [Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies] pathogens), show strong synergy with several antibiotics, and act by targeting a universal stress response in bacteria. Thus, these peptides represent a promising alternative treatment to conventional antibiotics and work effectively in animal models of biofilm-associated infections.

scholarly journals Antibiotic Susceptibility Study Of Metal-Gentamicin Complexes Against Staphylococcus Aureus Biofilms

2017 ◽  
Vol 16 (2) ◽  
Author(s):  
Intan Azura Shahdan ◽  
Fatimah Zahrah Mohd Sobri ◽  
Mohammad Faiz Hizzuan Hanapi ◽  
Hanani Ahmad Yusof ◽  
Fiona N.-F. How
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Susceptibility ◽  
Bacterial Species ◽  
Dental Biofilm ◽  
Planktonic Bacteria ◽  
Metal Contents ◽  
Susceptibility Study ◽  
Biofilm Bacteria ◽  
Dental Plaques ◽  
Conventional Antibiotics

Introduction: Dental plaque is a structurally and functionally organized biofilm. Modern molecular biological techniques have identified about 1000 different bacterial species in the dental biofilm, twice as many as can be cultured. Inherent resistance of biofilm bacteria to conventional antibiotics is alarming. It induces antibiotic resistance to an order of three or more in magnitude greater than those displayed by planktonic bacteria. Staphylococcus aureus is the most dominant bacterial species isolated from the saliva and dental plaques. One of the reasons for its pathogenicity is its ability to form biofilms. In this study, the resistance of S. aureus biofilms against a eries of metal-antibiotics, an alternative to the conventional antibiotics, was investigated. Materials and Methods: A series of metal-antibiotic complexes derived from gentamicin was synthesized to give metal-gentamicin complexes. The metal contents of all the compounds were determined using Atomic Absorption Spectroscopy (AAS). Antibiotic susceptibility testing of the gentamicin-antibiotic complexes against several strains of S. aureus biofilms was conducted using broth microdilution assay. Results: The results showed that S. aureus is susceptible against Co(II) and Fe(II) gentamicin complexes; all were tested at 0.25 to 1 mmol concentrations. Conclusion(s): Co(II) and Fe(II)-gentamicin complexes demonstrated antimicrobial activity.

scholarly journals A COMPARATIVE STUDY OF ANTIMICROBIAL PROFILE HAVING BROAD SPECTRUM BACTERIOCINS AGAINST ANTIBIOTICS

2017 ◽  
Vol 10 (9) ◽  
pp. 44 ◽  
Author(s):  
Sabiha Imran ◽  
Twinkle Gupta ◽  
Aarti Arora ◽  
Nilanjan Das
Keyword(s):  
Broad Spectrum ◽  
Cationic Peptides ◽  
Promising Alternative ◽  
Bacterial Diseases ◽  
Adverse Side Effects ◽  
Experimental Systems ◽  
Improper Use ◽  
Physical And Chemical

  Bacteriocins are ribosomally synthesized antimicrobial peptides produced by microbes owned by different eubacterial taxonomic branches. Most of them are small cationic membrane-active compounds that form pores in the targeted cells, disrupting membrane possibilities, and triggering cell fatality. The availability of small cationic peptides with antimicrobial activity is a protection strategy found not only in bacteria but also in plants and animals. The antibiotics which have extensive applications in the treatment of various bacterial diseases have developed alarming resistance against them in many pathogens due to improper use besides this antibiotics have adverse side effects also. There are an extensive variety of bacteriocins made by different bacterial genera have promising alternative to antibiotics that needs to be further studied to show the no existence of undesirable effects, which must be performed both in vitro and in vivo experimental systems. Most of the bacteriocin have narrow spectrum of their activity and effective only on the related species. There is an urgent need for the identification of broad-spectrum bacteriocins isolated from the species from different habitats that can be effective against both Gram-positive and Gram-negative pathogens. In this review, we focus on the main physical and chemical characteristics of broad-spectrum bacteriocin and discuss their application as an alternative option to antibiotics.

scholarly journals The Urinary Antibiotic 5-Nitro-8-Hydroxyquinoline (Nitroxoline) Reduces the Formation and Induces the Dispersal of Pseudomonas aeruginosa Biofilms by Chelation of Iron and Zinc

2012 ◽  
Vol 56 (11) ◽  
pp. 6021-6025 ◽  
Author(s):  
A. Sobke ◽  
M. Klinger ◽  
B. Hermann ◽  
S. Sachse ◽  
S. Nietzsche ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Broad Spectrum ◽  
Viable Cell ◽  
Antibiofilm Activity ◽  
Content Type ◽  
Cell Counts ◽  
Iron And Zinc ◽  
Chelation Of Iron

ABSTRACTSince cations have been reported as essential regulators of biofilm, we investigated the potential of the broad-spectrum antimicrobial and cation-chelator nitroxoline as an antibiofilm agent. Biofilm mass synthesis was reduced by up to 80% at sub-MIC nitroxoline concentrations inPseudomonas aeruginosa, and structures formed were reticulate rather than compact. In preformed biofilms, viable cell counts were reduced by 4 logs at therapeutic concentrations. Complexation of iron and zinc was demonstrated to underlie nitroxoline's potent antibiofilm activity.

scholarly journals ClyJ Is a Novel Pneumococcal Chimeric Lysin with a Cysteine- and Histidine-Dependent Amidohydrolase/Peptidase Catalytic Domain

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Hang Yang ◽  
Yujing Gong ◽  
Huaidong Zhang ◽  
Irina Etobayeva ◽  
Paulina Miernikiewicz ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
High Specificity ◽  
Multidrug Resistant ◽  
Penicillin G ◽  
Dependent Manner ◽  
Pneumococcal Infections ◽  
Promising Alternative ◽  
Content Type ◽  
Conventional Antibiotics

ABSTRACT Streptococcus pneumoniae is one of the leading pathogens that cause a variety of mucosal and invasive infections. With the increased emergence of multidrug-resistant S. pneumoniae, new antimicrobials with mechanisms of action different from conventional antibiotics are urgently needed. In this study, we identified a putative lysin (gp20) encoded by the Streptococcus phage SPSL1 using the LytA autolysin as a template. Molecular dissection of gp20 revealed a binding domain (GPB) containing choline-binding repeats (CBRs) that are high specificity for S. pneumoniae. By fusing GPB to the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain of the PlyC lysin, we constructed a novel chimeric lysin, ClyJ, with improved activity to the pneumococcal Cpl-1 lysin. No resistance was observed in S. pneumoniae strains after exposure to incrementally doubling concentrations of ClyJ for 8 continuous days in vitro. In a mouse bacteremia model using penicillin G as a control, a single intraperitoneal injection of ClyJ improved the survival rate of lethal S. pneumoniae-infected mice in a dose-dependent manner. Given its high lytic activity and safety profile, ClyJ may represent a promising alternative to combat pneumococcal infections.

scholarly journals Effects of a Novel Probiotic Combination on Pathogenic Bacterial-Fungal Polymicrobial Biofilms

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Christopher L. Hager ◽  
Nancy Isham ◽  
Kory P. Schrom ◽  
Jyotsna Chandra ◽  
Thomas McCormick ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Gut Microbiome ◽  
Biofilm Formation ◽  
Bacterial Species ◽  
Bacterial Flora ◽  
Confocal Scanning Laser Microscopy ◽  
Antibiofilm Activity ◽  
Content Type ◽  
Bowel Diseases ◽  
Inflammatory Bowel

ABSTRACTDysbiosis of the gut microbiome has been implicated in inflammatory bowel diseases. We have shown that levels ofCandida tropicalis, along with those ofEscherichia coliandSerratia marcescens, are significantly elevated in Crohn’s disease (CD) patients. Here, we evaluated the ability of a novel probiotic to prevent and treat polymicrobial biofilms (PMB) formed byC. tropicaliswithE. coliandS. marcescens. SinceCandida albicanshas been reported to be elevated in CD patients, we investigated the interactions ofC. albicanswith these bacterial species in biofilm formation. We determined whether the interaction betweenCandidaspp. and bacteria is specific by usingTrichosporon inkinandSaccharomyces fibuligeraas comparators. Additionally, the effects of probiotics onC. albicansgermination and biofilm formation were determined. To determine the ability of the probiotic to prevent or treat mature biofilms, probiotic filtrate was added to the PMB at early (prevention) and mature (treatment) phases. Biofilm thickness and architecture were assessed by confocal scanning laser microscopy. The effects of the probiotic on germination were evaluated in the presence of serum. Exposure ofC. tropicalisPMB to probiotic filtrate reduced biofilm matrix, decreased thickness, and inhibited hyphal formation. We showed thatC. albicansorC. tropicalisformed significantly thicker PMB than control biofilms, indicating that this interaction isCandidaspecific. Treatment with probiotic filtrate inhibitedC. albicansgermination and prevented/treatedC. albicansPMB. The designed probiotic may have utility in the management of biofilm-associated gastrointestinal diseases such as Crohn’s and colorectal cancer.IMPORTANCEThe effects of diversity of the gut microbiome on inflammation have centered mainly on bacterial flora. Recent research has implicated fungal species and their interactions with other organisms in the inflammatory process. New ways to restore microbial balance in the gut are being explored. Our goal was to identify beneficial probiotic strains that would antagonize these fungal and bacterial pathogens that are elevated in the inflamed gut, and which also have antibiofilm activity. Fungus-bacterium correlation analysis allowed us to identify candidate probiotic species that can antagonize microbial pathogens, which we subsequently incorporated into a novel probiotic formulation. Amylase, which is known to have some antibiofilm activity, was also added to the probiotic mixture. This novel probiotic may have utility for the management of inflammatory bowel diseases by disrupting polymicrobial biofilm formation.

On the naming of monsters

2014 ◽  
Vol 33 (7) ◽  
pp. 575-594
Author(s):  
Brian P. Bloomfield ◽  
Theo Vurdubakis
Keyword(s):  
Social Organization ◽  
Reproductive Technology ◽  
Human Reproduction ◽  
Moral Conflicts ◽  
Content Type ◽  
The Past ◽  
Cultural Expectations ◽  
Novel Approach ◽  
Recent Developments ◽  
Quantitative Examination

Purpose – The pupose of this paper is twofold. First, to consider the cultural reception of recent developments in genetic technology and human reproduction, particularly in relation to the prospect of human cloning and the advent of the “designer human”; and second, to explore the ways in which public discussion of these developments presuppose and recast issues of diversity, difference and (in)equality. Design/methodology/approach – The research draws upon UK print media sources (broadsheet and tabloid newspapers) over the past two decades to examine the ways in which cultural expectations concerning developments in reproductive technology are commonly expressed. It does not aim at a quantitative examination of the content of what was said; rather it seeks to explore how it was said and thus the discursive resources that were employed in doing so. Findings – The paper suggests that images of “technology” function simultaneously as “mirrors of society”, providing a means for articulating and rhetorically rehearsing the various philosophical antinomies and moral conflicts that characterize social organization. Originality/value – The paper adopts a novel approach to the question of diversity, difference and (in)equality by considering the “monsters” discursively associated with recent developments in genetic and reproductive technology as well as the “monstrous” forms of social organization that they foreshadow.

scholarly journals A Screen for and Validation of Prodrug Antimicrobials

2013 ◽  
Vol 58 (3) ◽  
pp. 1410-1419 ◽  
Author(s):  
Laura E. Fleck ◽  
E. Jeffrey North ◽  
Richard E. Lee ◽  
Lawrence R. Mulcahy ◽  
Gabriele Casadei ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Unmet Need ◽  
Host Cells ◽  
Gram Negative Bacteria ◽  
Irreversible Binding ◽  
Chronic Infections ◽  
Persister Cells ◽  
Content Type ◽  
Excellent Activity ◽  
Conventional Antibiotics

ABSTRACTThe rise of resistant pathogens and chronic infections tolerant to antibiotics presents an unmet need for novel antimicrobial compounds. Identifying broad-spectrum leads is challenging due to the effective penetration barrier of Gram-negative bacteria, formed by an outer membrane restricting amphipathic compounds, and multidrug resistance (MDR) pumps. In chronic infections, pathogens are shielded from the immune system by biofilms or host cells, and dormant persisters tolerant to antibiotics are responsible for recalcitrance to chemotherapy with conventional antibiotics. We reasoned that the dual need for broad-spectrum and sterilizing compounds could be met by developing prodrugs that are activated by bacterium-specific enzymes and that these generally reactive compounds could kill persisters and accumulate over time due to irreversible binding to targets. We report the development of a screen for prodrugs, based on identifying compounds that nonspecifically inhibit reduction of the viability dye alamarBlue, and then eliminate generally toxic compounds by testing for cytotoxicity. A large pilot of 55,000 compounds againstEscherichia coliproduced 20 hits, 3 of which were further examined. One compound, ADC111, is an analog of a known nitrofuran prodrug nitrofurantoin, and its activity depends on the presence of activating enzymes nitroreductases. ADC112 is an analog of another known antimicrobial tilbroquinol with unknown mechanism of action, and ADC113 does not belong to an approved class. All three compounds had a good spectrum and showed good to excellent activity against persister cells in biofilm and stationary cultures. These results suggest that screening for overlooked prodrugs may present a viable platform for antimicrobial discovery.

scholarly journals Polycationic Silver Nanoclusters Comprising Nanoreservoirs of Ag+-Ions with High Antimicrobial and Antibiofilm Activity

2021 ◽  
Author(s):  
Hanif Haidari ◽  
Richard Bright ◽  
Zlatko Kopecki ◽  
Peter Zilm ◽  
Sanjay Garg ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Bacterial Resistance ◽  
Anaerobic Bacteria ◽  
Silver Ions ◽  
Silver Nanoclusters ◽  
Antibiofilm Activity ◽  
Ion Release ◽  
Wide Range ◽  
Multiple Species ◽  
Conventional Antibiotics

Abstract The evolving resistance of bacteria to common antibiotics has prompted urgent demand for alternative antibacterial agents that not only control infections but are also able to prevent bacterial resistance. Silver-based nanoantibiotics are rapidly developing as promising alternatives because of their broad-spectrum antimicrobial activity, multifaceted mechanism of action and good biocompatibility. Ideally, to remain potent against a wide range of drug-resistant and anaerobic bacteria, silver-based nanoantibiotics should easily penetrate through the bacterial cell walls and actively release silver ions. However, most of the currently available silver nanomaterials are limited by their negative surface charge and the requirement of oxygen/water for the silver ion release. Here, a novel silver nanoparticle consisting of unique features including (i) ultra-small size (< 3 nm), (ii) high monodispersity, (iii) high percentage (> 50%) of silver ions content (i.e., Ag+- nanoreservoir) and (iv) polycationic surface layer was developed (referred as pAgNCs). The nanomaterial was very potent in eliminating a range of common Gram-negative and Gram-positive pathogens. Furthermore, the pAgNCs were also highly efficient in eradicating established and matured biofilms, including those composed of multiple species. The pAgNCs also showed greatly enhanced antibacterial efficacy against anaerobic bacteria such as F. nucleatum and S. sanguinis, which was attributed to the abundance of Ag+ ions in the nanoreservoir. Importantly, the pAgNCs showed a strong capacity to significantly delay the development of bacterial resistance when compared to similar-sized negatively charged AgNPs or conventional antibiotics. This study demonstrates a novel design strategy that can lay the foundation for the development of future highly potent nano-antibiotics effective against broad-spectrum of pathogens and biofilms needed in many everyday life applications and industries.

scholarly journals HJH-1, a Broad-Spectrum Antimicrobial Activity and Low Cytotoxicity Antimicrobial Peptide

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2026 ◽  
Author(s):  
Qing Wang ◽  
Yanzhao Xu ◽  
Mengmeng Dong ◽  
Bolin Hang ◽  
Yawei Sun ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Broad Spectrum ◽  
Ph Value ◽  
Bacterial Species ◽  
Membrane Integrity ◽  
Resistant Bacteria ◽  
Bacterial Membrane ◽  
Α Subunit ◽  
Promising Alternative

With the overuse of antibiotics, multidrug-resistant bacteria pose a significant threat to human health. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. This study examines the antimicrobial and membrane activity of HJH-1, a cationic peptide derived from the hemoglobin α-subunit of bovine erythrocytes P3. HJH-1 shows potent antimicrobial activity against different bacterial species associated with infection and causes weaker hemolysis of erythrocytes, at least five times the minimum inhibitory concentration (MIC). HJH-1 has good stability to tolerance temperature, pH value, and ionic strength. The anionic membrane potential probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)] and propidium iodide are used as indicators of membrane integrity. In the presence of HJH-1 (1× MIC), Escherichia coli membranes rapidly depolarise, whereas red blood cells show gradual hyperpolarisation. Scanning electron microscopy and transmission electron micrographs show that HJH-1 (1× MIC) damaged the membranes of Escherichia coli, Staphylococcus aureus, and Candida albicans. In conclusion, HJH-1 damages the integrity of the bacterial membrane, preventing the growth of bacteria. HJH-1 has broad-spectrum antibacterial activity, and these activities are performed by changing the normal cell transmembrane potential and disrupting the integrity of the bacterial membrane.

scholarly journals Surfing Motility: a Conserved yet Diverse Adaptation among Motile Bacteria

2018 ◽  
Vol 200 (23) ◽  
Author(s):  
Evelyn Sun ◽  
Sijie Liu ◽  
Robert E. W. Hancock
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Broad Spectrum ◽  
Proteus Mirabilis ◽  
Salmonella Enterica ◽  
Bacterial Species ◽  
Content Type ◽  
Adaptive Resistance ◽  
Sensing Systems

ABSTRACTBacterial rapid surfing motility is a novel surface adaptation ofPseudomonas aeruginosain the presence of the glycoprotein mucin. Here, we show that other Gram-negative motile bacterial species, includingEscherichia coli,Salmonella enterica,Vibrio harveyi,Enterobacter cloacae, andProteus mirabilis, also exhibit the physical characteristics of surfing on the surface of agar plates containing 0.4% mucin, where surfing motility was generally more rapid and less dependent on medium viscosity than was swimming motility. As previously observed inPseudomonas aeruginosa, all surfing species exhibited some level of broad-spectrum adaptive resistance, although the antibiotics to which they demonstrated surfing-mediated resistance differed. Surfing motility inP. aeruginosawas found to be dependent on the quorum-sensing systems of this organism; however, this aspect was not conserved in other tested bacterial species, includingV. harveyiandS. enterica, as demonstrated by assaying specific quorum-sensing mutants. Thus, rapid surfing motility is a complex surface growth adaptation that is conserved in several motile bacteria, involves flagella, and leads to diverse broad-spectrum antibiotic resistance, but it is distinct in terms of dependence on quorum sensing.IMPORTANCEThis study showed for the first time that surfing motility, a novel form of surface motility first discovered inPseudomonas aeruginosaunder artificial cystic fibrosis conditions, including the presence of high mucin content, is conserved in other motile bacterial species known to be mucosa-associated, includingEscherichia coli,Salmonella enterica, andProteus mirabilis. Here, we demonstrated that key characteristics of surfing, including the ability to adapt to various viscous environments and multidrug adaptive resistance, are also conserved. Using mutagenesis assays, we also identified the importance of all three known quorum-sensing systems, Las, Rhl, and Pqs, inP. aeruginosain regulating surfing motility, and we also observed a conserved dependence of surfing on flagella in certain species.

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