scholarly journals Anti-infective Effects of a Fish-Derived Antimicrobial Peptide Against Drug-Resistant Bacteria and Its Synergistic Effects With Antibiotic

2020 ◽  
Vol 11 ◽  
Author(s):  
Yue Chen ◽  
Jing Wu ◽  
Honglan Cheng ◽  
Yue Dai ◽  
Yipeng Wang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Peptide ◽  
Synergistic Effects ◽  
Head Kidney ◽  
Resistant Bacteria ◽  
Bacterial Membrane ◽  
Microbial Infection ◽  
Antibiotic Resistant ◽  
Sytox Green

Antimicrobial peptides (AMPs) play pivotal roles in protecting against microbial infection in fish. However, AMPs from topmouth culter (Erythroculter ilishaeformis) are rarely known. In our study, we isolated an AMP from the head kidney of topmouth culter, which belonged to liver-expressed antimicrobial peptide 2 (LEAP-2) family. Topmouth culter LEAP-2 showed inhibitory effects on aquatic bacterial growth, including antibiotic-resistant bacteria, with minimal inhibitory concentration values ranging from 18.75 to 150 μg/ml. It was lethal for Aeromonas hydrophila (resistant to ampicillin), and took less than 60 min to kill A. hydrophila at a concentration of 5 × MIC. Scanning electron microscope (SEM) and SYTOX Green uptake assay indicated that it impaired the integrity of bacterial membrane by eliciting pore formation, thereby increasing the permeabilization of bacterial membrane. In addition, it showed none inducible drug resistance to aquatic bacteria. Interestingly, it efficiently delayed ampicillin-induced drug resistance in Vibrio parahaemolyticus (sensitive to ampicillin) and sensitized ampicillin-resistant bacteria to ampicillin. The chequerboard assay indicated that topmouth culter LEAP-2 generated synergistic effects with ampicillin, indicating the combinational usage potential of topmouth culter LEAP-2 with antibiotics. As expected, topmouth culter LEAP-2 significantly alleviated ampicillin-resistant A. hydrophila infection in vivo, and enhanced the therapeutic efficacy of ampicillin against A. hydrophila in vivo. Our findings provide a fish innate immune system-derived peptide candidate for the substitute of antibiotics and highlight its potential for application in antibiotic-resistant bacterial infection in aquaculture industry.

scholarly journals Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications

2021 ◽  
Vol 9 ◽  
Author(s):  
Thanh Chung Pham ◽  
Van-Nghia Nguyen ◽  
Yeonghwan Choi ◽  
Dongwon Kim ◽  
Ok-Sang Jung ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Stokes Shift ◽  
Fluorescence Emission ◽  
Antibacterial Activities ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Fluorogenic Probe ◽  
High Fluorescence

The ability to detect hypochlorite (HOCl/ClO−) in vivo is of great importance to identify and visualize infection. Here, we report the use of imidazoline-2-thione (R1SR2) probes, which act to both sense ClO− and kill bacteria. The N2C=S moieties can recognize ClO− among various typical reactive oxygen species (ROS) and turn into imidazolium moieties (R1IR2) via desulfurization. This was observed through UV–vis absorption and fluorescence emission spectroscopy, with a high fluorescence emission quantum yield (ՓF = 43–99%) and large Stokes shift (∆v∼115 nm). Furthermore, the DIM probe, which was prepared by treating the DSM probe with ClO−, also displayed antibacterial efficacy toward not only Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) but also methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase–producing Escherichia coli (ESBL-EC), that is, antibiotic-resistant bacteria. These results suggest that the DSM probe has great potential to carry out the dual roles of a fluorogenic probe and killer of bacteria.

scholarly journals Better living through chemistry: Addressing emerging antibiotic resistance

2018 ◽  
Vol 243 (6) ◽  
pp. 538-553 ◽  
Author(s):  
Nathan P Coussens ◽  
Ashley L Molinaro ◽  
Kayla J Culbertson ◽  
Tyler Peryea ◽  
Gergely Zahoránszky-Köhalmi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Human Health ◽  
Small Molecule ◽  
Bacterial Infections ◽  
Public Investment ◽  
Antibiotic Use ◽  
Unintended Consequences ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Small Molecule Drugs

The increasing emergence of multidrug-resistant bacteria is recognized as a major threat to human health worldwide. While the use of small molecule antibiotics has enabled many modern medical advances, it has also facilitated the development of resistant organisms. This minireview provides an overview of current small molecule drugs approved by the US Food and Drug Administration (FDA) for use in humans, the unintended consequences of antibiotic use, and the mechanisms that underlie the development of drug resistance. Promising new approaches and strategies to counter antibiotic-resistant bacteria with small molecules are highlighted. However, continued public investment in this area is critical to maintain an edge in our evolutionary “arms race” against antibiotic-resistant microorganisms. Impact statement The alarming increase in antibiotic-resistant microorganisms is a rapidly emerging threat to human health throughout the world. Historically, small molecule drugs have played a major role in controlling bacterial infections and they continue to offer tremendous potential in countering resistant organisms. This minireview provides a broad overview of the relevant issues, including the diversity of FDA-approved small molecule drugs and mechanisms of drug resistance, unintended consequences of antibiotic use, the current state of development for small molecule antibacterials and financial challenges that impact progress towards novel therapies. The content will be informative to diverse stakeholders, including clinicians, basic scientists, translational scientists and policy makers, and may be used as a bridge between these key players to advance the development of much-needed therapeutics.

scholarly journals Characterization and Therapeutic Potential of Bacteriophage-Encoded Polysaccharide Depolymerases with β Galactosidase Activity against Klebsiella pneumoniae K57 Capsular Type

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 732
Author(s):  
Nikolay V. Volozhantsev ◽  
Anna M. Shpirt ◽  
Alexander I. Borzilov ◽  
Ekaterina V. Komisarova ◽  
Valentina M. Krasilnikova ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Therapeutic Potential ◽  
Resistant Bacteria ◽  
Capsular Type ◽  
Antibiotic Resistant ◽  
Promising Tool ◽  
Hip Infection ◽  
Immune Attack ◽  
Hydrolytic Mechanism

Bacteriophages and phage enzymes are considered as possible alternatives to antibiotics in the treatment of infections caused by antibiotic-resistant bacteria. Due to the ability to cleave the capsular polysaccharides (CPS), one of the main virulence factors of Klebsiella pneumoniae, phage depolymerases, has potential in the treatment of K. pneumoniae infections. Here, we characterized in vivo two novel phage-encoded polysaccharide depolymerases as therapeutics against clinical isolates of K. pneumoniae. The depolymerases Dep_kpv79 and Dep_kpv767 encoded by Klebsiella phages KpV79 (Myoviridae; Jedunavirus) and KpV767 (Autographiviridae, Studiervirinae, Przondovirus), respectively, were identified as specific β-galactosidases that cleave the K. pneumoniae K57 type CPS by the hydrolytic mechanism. They were found to be highly effective at combating sepsis and hip infection caused by K. pneumoniae in lethal mouse models. Here, 80–100% of animals were protected against death by a single dose (e.g., 50 μg/mouse) of the enzyme injected 0.5 h after infection by K. pneumoniae strains of the K57 capsular type. The therapeutic effect of the depolymerases is because they strip the capsule and expose the underlying bacterium to the immune attack such as complement-mediated killing. These data provide one more confirmation that phage polysaccharide depolymerases represent a promising tool for antimicrobial therapy.

scholarly journals In vitro Antimicrobial Activity of Acne Drugs Against Skin-Associated Bacteria

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mark A. T. Blaskovich ◽  
Alysha G. Elliott ◽  
Angela M. Kavanagh ◽  
Soumya Ramu ◽  
Matthew A. Cooper
Keyword(s):  
Antimicrobial Activity ◽  
Resistant Bacteria ◽  
Microbial Infection ◽  
Antibiotic Resistant ◽  
Drug Resistant Bacteria ◽  
Cutibacterium Acnes ◽  
Common Skin ◽  
Sebum Production ◽  
Resistant Strains

Abstract Acne is a common skin affliction that involves excess sebum production and modified lipid composition, duct blockage, colonization by bacteria, and inflammation. Acne drugs target one or more of these steps, with antibiotics commonly used to treat the microbial infection for moderate to severe cases. Whilst a number of other acne therapies are purported to possess antimicrobial activity, this has been poorly documented in many cases. We conducted a comparative analysis of the activity of common topical acne drugs against the principal etiological agent associated with acne: the aerotolerant anaerobic Gram-positive organism Propionibacterium acnes (recently renamed as Cutibacterium acnes). We also assessed their impact on other bacteria that could also be affected by topical treatments, including both antibiotic-sensitive and antibiotic-resistant strains, using broth microdilution assay conditions. Drugs designated specifically as antibiotics had the greatest potency, but lost activity against resistant strains. The non-antibiotic acne agents did possess widespread antimicrobial activity, including against resistant strains, but at substantially higher concentrations. Hence, the antimicrobial activity of non-antibiotic acne agents may provide protection against a background of increased drug-resistant bacteria.

scholarly journals Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs

Toxins ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 255 ◽  
Author(s):  
Clara Pérez-Peinado ◽  
Sira Defaus ◽  
David Andreu
Keyword(s):  
Therapeutic Potential ◽  
State Of The Art ◽  
Resistant Bacteria ◽  
Snake Venoms ◽  
Antibiotic Resistant ◽  
Anticancer Peptides ◽  
Therapeutic Development ◽  
Drug Leads

For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and blood abnormalities are on the market. Likewise, far more SV compounds and their mimetics are under investigation today for diverse therapeutic applications, including antibiotic-resistant bacteria and cancer. In this review, we analyze the state of the art regarding SV-derived compounds with therapeutic potential, focusing on the development of antimicrobial and anticancer drugs. Specifically, information about SV peptides experimentally validated or predicted to act as antimicrobial and anticancer peptides (AMPs and ACPs, respectively) has been collected and analyzed. Their principal activities both in vitro and in vivo, structures, mechanisms of action, and attempts at sequence optimization are discussed in order to highlight their potential as drug leads.

scholarly journals Phage steering of antibiotic-resistance evolution in the bacterial pathogen, Pseudomonas aeruginosa

2020 ◽  
Vol 2020 (1) ◽  
pp. 148-157 ◽  
Author(s):  
James Gurney ◽  
Léa Pradier ◽  
Joanne S Griffin ◽  
Claire Gougat-Barbera ◽  
Benjamin K Chan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Bacterial Pathogen ◽  
Antibiotic Sensitivity ◽  
Resistant Bacteria ◽  
Phage Resistance ◽  
Antibiotic Resistant ◽  
Trade Off

Abstract Background and objectives Antimicrobial resistance is a growing global concern and has spurred increasing efforts to find alternative therapeutics. Bacteriophage therapy has seen near constant use in Eastern Europe since its discovery over a century ago. One promising approach is to use phages that not only reduce bacterial pathogen loads but also select for phage resistance mechanisms that trade-off with antibiotic resistance—so called ‘phage steering’. Methodology Recent work has shown that the phage OMKO1 can interact with efflux pumps and in so doing select for both phage resistance and antibiotic sensitivity of the pathogenic bacterium Pseudomonas aeruginosa. We tested the robustness of this approach to three different antibiotics in vitro (tetracycline, erythromycin and ciprofloxacin) and one in vivo (erythromycin). Results We show that in vitro OMKO1 can reduce antibiotic resistance of P. aeruginosa (Washington PAO1) even in the presence of antibiotics, an effect still detectable after ca.70 bacterial generations in continuous culture with phage. Our in vivo experiment showed that phage both increased the survival times of wax moth larvae (Galleria mellonella) and increased bacterial sensitivity to erythromycin. This increased antibiotic sensitivity occurred both in lines with and without the antibiotic. Conclusions and implications Our study supports a trade-off between antibiotic resistance and phage sensitivity. This trade-off was maintained over co-evolutionary time scales even under combined phage and antibiotic pressure. Similarly, OMKO1 maintained this trade-off in vivo, again under dual phage/antibiotic pressure. Our findings have implications for the future clinical use of steering in phage therapies. Lay Summary: Given the rise of antibiotic-resistant bacterial infection, new approaches to treatment are urgently needed. Bacteriophages (phages) are bacterial viruses. The use of such viruses to treat infections has been in near-continuous use in several countries since the early 1900s. Recent developments have shown that these viruses are not only effective against routine infections but can also target antibiotic resistant bacteria in a novel, unexpected way. Similar to other lytic phages, these so-called ‘steering phages’ kill the majority of bacteria directly. However, steering phages also leave behind bacterial variants that resist the phages, but are now sensitive to antibiotics. Treatment combinations of these phages and antibiotics can now be used to greater effect than either one independently. We evaluated the impact of steering using phage OMKO1 and a panel of three antibiotics on Pseudomonas aeruginosa, an important pathogen in hospital settings and in people with cystic fibrosis. Our findings indicate that OMKO1, either alone or in combination with antibiotics, maintains antibiotic sensitivity both in vitro and in vivo, giving hope that phage steering will be an effective treatment option against antibiotic-resistant bacteria.

Transferable drug resistance in bacteria from fish-farm sediments

1992 ◽  
Vol 38 (10) ◽  
pp. 1061-1065 ◽  
Author(s):  
Ruth-Anne Sandaa ◽  
Vigdis Lid Torsvik ◽  
Jostein Goksøyr
Keyword(s):  
Drug Resistance ◽  
Antibacterial Agents ◽  
Resistant Bacteria ◽  
Agarose Gel Electrophoresis ◽  
Bacterial Isolates ◽  
Fish Farms ◽  
Transfer Resistance ◽  
Antibiotic Resistant ◽  
Antimicrobial Resistance Genes ◽  
Direct Cell

Antibiotic-resistant bacteria were isolated from sediment samples collected beneath two fish farms west of Bergen (Norway). The samples were collected just after the fish had been treated with oxytetracycline. Eighty-four bacterial isolates were tested for susceptibility to antibacterial agents. Most of the isolates were resistant to oxytetracycline, kanamycin, and sulfamethoxazole. Transferable plasmid-related resistance was shown by direct cell transfer and agarose gel electrophoresis. Among 34 multiple-resistant isolates, 7 isolates were able to transfer resistance to Escherichia coli HB101. Phenotypical characterization indicated that these seven isolates belonged to the genera Vibrio and Pseudomonas. The results indicate that sediments beneath fish farms may serve as a reservoir for transferable antimicrobial resistance genes. Key words: drug resistance, gene transfer, marine sediment bacteria.

In Vitro and In Vivo Efficacy of Catheters Impregnated With Antiseptics or Antibiotics: Evaluation of the Risk of Bacterial Resistance to the Antimicrobials in the Catheters

2001 ◽  
Vol 22 (10) ◽  
pp. 640-646 ◽  
Author(s):  
Lester A. Sampath ◽  
Suhas M. Tambe ◽  
Shanta M. Modak
Keyword(s):  
Bacterial Resistance ◽  
Test Organism ◽  
Similar Efficacy ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
In Vivo Efficacy ◽  
Development Of Resistance ◽  
Zones Of Inhibition

AbstractObjective:To compare the efficacy of a new antiseptic catheter containing silver sulfadiazine and chlorhexidine on the external surface and chlorhexidine in the lumens to an antibiotic catheter impregnated with minocycline and rifampin on its external and luminal surfaces.Design:Experimental trial.Methods:Antimicrobial spectrum of catheters was determined by zones of inhibition. Resistance to luminal colonization was tested in vitro by locking catheter lumens withStaphylococcus epidermidisorStaphylococcus aureusculture after 7 days of perfusion. In vitro development of resistance to the antiseptic or antibiotic combination used in catheters was investigated. In vivo efficacy was tested (rat subcutaneous model) by challenge with sensitive or antibiotic-resistant bacteria.Results:Antiseptic and antibiotic catheters exhibited broad-spectrum action. However, antibiotic catheters were not effective againstCandidaspecies andPseudomonas aeruginosa.Both catheters prevented luminal colonization. Compared to controls, both test catheters resisted colonization when challenged withS aureus7 and 14 days' postimplant (P<.05).Repeated in vitro exposure ofS epidermidisculture to the antibiotic and antiseptic combinations led to small increases in the minimum inhibitory concentration (15 times and 2 times, respectively). Unlike the antibiotic catheter, the in vitro and in vivo activity of the antiseptic catheter was unaffected by the resistance profile of the test organism. Antiseptic catheters were more effective than antibiotic catheters in preventing colonization by rifampin-resistantS epidermidisin vivo (P<.05).Conclusions:Antiseptic and antibiotic catheters exhibit similar efficacy; however, when challenged with a rifampin-resistant strain, the antibiotic catheter appeared to be more susceptible to colonization than the antiseptic device.

scholarly journals A dose response model for quantifying the infection risk of antibiotic-resistant bacteria

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Srikiran Chandrasekaran ◽  
Sunny C. Jiang
Keyword(s):  
Dose Response ◽  
Human Health Risk ◽  
Infection Risk ◽  
Resistant Bacteria ◽  
Microbial Infection ◽  
Total Risk ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Regulatory Policies

AbstractQuantifying the human health risk of microbial infection helps inform regulatory policies concerning pathogens, and the associated public health measures. Estimating the infection risk requires knowledge of the probability of a person being infected by a given quantity of pathogens, and this relationship is modeled using pathogen specific dose response models (DRMs). However, risk quantification for antibiotic-resistant bacteria (ARB) has been hindered by the absence of suitable DRMs for ARB. A new approach to DRMs is introduced to capture ARB and antibiotic-susceptible bacteria (ASB) dynamics as a stochastic simple death (SD) process. By bridging SD with data from bench experiments, we demonstrate methods to (1) account for the effect of antibiotic concentrations and horizontal gene transfer on risk; (2) compute total risk for samples containing multiple bacterial types (e.g., ASB, ARB); and (3) predict if illness is treatable with antibiotics. We present a case study of exposure to a mixed population of Gentamicin-susceptible and resistant Escherichia coli and predict the health outcomes for varying Gentamicin concentrations. Thus, this research establishes a new framework to quantify the risk posed by ARB and antibiotics.

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