scholarly journals Bystander Phage Therapy: Inducing Host-Associated Bacteria to Produce Antimicrobial Toxins against the Pathogen Using Phages

Antibiotics ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 105 ◽  
Author(s):  
T. Brady ◽  
Christopher Fajardo ◽  
Bryan Merrill ◽  
Jared Hilton ◽  
Kiel Graves ◽  
...  

Brevibacillus laterosporus is often present in beehives, including presence in hives infected with the causative agent of American Foulbrood (AFB), Paenibacillus larvae. In this work, 12 B. laterosporus bacteriophages induced bactericidal products in their host. Results demonstrate that P. larvae is susceptible to antimicrobials induced from field isolates of the bystander, B. laterosporus. Bystander antimicrobial activity was specific against the pathogen and not other bacterial species, indicating that the production was likely due to natural competition between the two bacteria. Three B. laterosporus phages were combined in a cocktail to treat AFB. Healthy hives treated with B. laterosporus phages experienced no difference in brood generation compared to control hives over 8 weeks. Phage presence in bee larvae after treatment rose to 60.8 ± 3.6% and dropped to 0 ± 0.8% after 72 h. In infected hives the recovery rate was 75% when treated, however AFB spores were not susceptible to the antimicrobials as evidenced by recurrence of AFB. We posit that the effectiveness of this treatment is due to the production of the bactericidal products of B. laterosporus when infected with phages resulting in bystander-killing of P. larvae. Bystander phage therapy may provide a new avenue for antibacterial production and treatment of disease.

2005 ◽  
Vol 71 (11) ◽  
pp. 7551-7555 ◽  
Author(s):  
Elke Genersch ◽  
Ainura Ashiralieva ◽  
Ingemar Fries

ABSTRACT Virulence variations of Paenibacillus larvae subsp. larvae, the causative agent of American foulbrood disease of honeybees, were investigated by analysis of 16 field isolates of this pathogen, belonging to three previously characterized genotypes, as well as the type strain (ATCC 9545) of P. larvae subsp. larvae, with exposure bioassays. We demonstrated that the strain-specific 50% lethal concentrations varied within an order of magnitude and that differences in amount of time for the pathogen to kill 100% of the infected hosts (LT100) correlated with genotype. One genotype killed rather quickly, with a mean LT100 of 7.8 ± 1.7 days postinfection, while the other genotypes acted more slowly, with mean LT100s of 11.2 ± 0.8 and 11.6 ± 0.6 days postinfection.


2009 ◽  
Vol 1 (2) ◽  
Author(s):  
Risa Nofiani ◽  
Siti Nurbetty ◽  
Ajuk Sapar

<p>The increase of issues on the antibiotics resistant pathogenic bacteria has triggered high exploration for new antimicrobial compounds. One of the potential sources is sponge-associated bacteria. The aim of this study was to get sponge-associated bacteria extract containing antimicrobial activities. On the basis screening of antimicrobial activity using by streaking on agar medium, there were two potential isolates with antimicrobial activities namely LCS1 and LCS2. The two isolates were cultivated,then secondary metabolite product were extracted using methanol as a solvent. Minimum inhibitory concentrations (MICs) of extract LCS 1 were 1,000 μg/well for S. aureus, 950 μg/well for Salmonella sp.and 800 μg/well for Bacillus subtilis. Minimum inhibitory concentrations of extract LCS 2 were 500 μg/well for S. aureus, 1,050 μg/well for Salmonella sp., 750 μg/well for Bacillus subtilis, 350 μg/well for P. aeruginosa, 750 μg/sumur terhadap B. subtilis. Based on the MIC values, the two assay extracts have a relatively low antimicrobial activity.</p> <p>Keywords:Antimicrobial,Sponges associated bacteria,MICs</p>


2020 ◽  
Vol 20 (29) ◽  
pp. 2681-2691
Author(s):  
Athina Geronikaki ◽  
Victor Kartsev ◽  
Phaedra Eleftheriou ◽  
Anthi Petrou ◽  
Jasmina Glamočlija ◽  
...  

Background: Although a great number of the targets of antimicrobial therapy have been achieved, it remains among the first fields of pharmaceutical research, mainly because of the development of resistant strains. Docking analysis may be an important tool in the research for the development of more effective agents against specific drug targets or multi-target agents 1-3. Methods: In the present study, based on docking analysis, ten tetrahydrothiazolo[2,3-a]isoindole derivatives were chosen for the evaluation of the antimicrobial activity. Results: All compounds showed antibacterial activity against eight Gram-positive and Gram-negative bacterial species being, in some cases, more potent than ampicillin and streptomycin against all species. The most sensitive bacteria appeared to be S. aureus and En. Cloacae, while M. flavus, E. coli and P. aeruginosa were the most resistant ones. The compounds were also tested for their antifungal activity against eight fungal species. All compounds exhibited good antifungal activity better than reference drugs bifonazole (1.4 – 41 folds) and ketoconazole (1.1 – 406 folds) against all fungal species. In order to elucidate the mechanism of action, docking studies on different antimicrobial targets were performed. Conclusion: According to docking analysis, the antifungal activity can be explained by the inhibition of the CYP51 enzyme for most compounds with a better correlation of the results obtained for the P.v.c. strain (linear regression between estimated binding Energy and log(1/MIC) with R 2 =0.867 and p=0.000091 or R 2 = 0.924, p= 0.000036, when compound 3 is excluded.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Chelsea A. Weitekamp ◽  
Allison Kvasnicka ◽  
Scott P. Keely ◽  
Nichole E. Brinkman ◽  
Xia Meng Howey ◽  
...  

Abstract Background Across taxa, animals with depleted intestinal microbiomes show disrupted behavioral phenotypes. Axenic (i.e., microbe-free) mice, zebrafish, and fruit flies exhibit increased locomotor behavior, or hyperactivity. The mechanism through which bacteria interact with host cells to trigger normal neurobehavioral development in larval zebrafish is not well understood. Here, we monoassociated zebrafish with either one of six different zebrafish-associated bacteria, mixtures of these host-associates, or with an environmental bacterial isolate. Results As predicted, the axenic cohort was hyperactive. Monoassociation with three different host-associated bacterial species, as well as with the mixtures, resulted in control-like locomotor behavior. Monoassociation with one host-associate and the environmental isolate resulted in the hyperactive phenotype characteristic of axenic larvae, while monoassociation with two other host-associated bacteria partially blocked this phenotype. Furthermore, we found an inverse relationship between the total concentration of bacteria per larvae and locomotor behavior. Lastly, in the axenic and associated cohorts, but not in the larvae with complex communities, we detected unexpected bacteria, some of which may be present as facultative predators. Conclusions These data support a growing body of evidence that individual species of bacteria can have different effects on host behavior, potentially related to their success at intestinal colonization. Specific to the zebrafish model, our results suggest that differences in the composition of microbes in fish facilities could affect the results of behavioral assays within pharmacological and toxicological studies.


2021 ◽  
Vol 9 (3) ◽  
pp. 509
Author(s):  
Amanda Carroll-Portillo ◽  
Henry C. Lin

Conventional phage therapy using bacteriophages (phages) for specific targeting of pathogenic bacteria is not always useful as a therapeutic for gastrointestinal (GI) dysfunction. Complex dysbiotic GI disorders such as small intestinal bowel overgrowth (SIBO), ulcerative colitis (UC), or Crohn’s disease (CD) are even more difficult to treat as these conditions have shifts in multiple populations of bacteria within the microbiome. Such community-level structural changes in the gut microbiota may require an alternative to conventional phage therapy such as fecal virome transfer or a phage cocktail capable of targeting multiple bacterial species. Additionally, manipulation of the GI microenvironment may enhance beneficial bacteria–phage interactions during treatment. Mucin, produced along the entire length of the GI tract to protect the underlying mucosa, is a prominent contributor to the GI microenvironment and may facilitate bacteria–phage interactions in multiple ways, potentially serving as an adjunct during phage therapy. In this review, we will describe what is known about the role of mucin within the GI tract and how its facilitation of bacteria–phage interactions should be considered in any effort directed at optimizing effectiveness of a phage therapy for gastrointestinal dysbiosis.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1141
Author(s):  
Noha M. Elhosseiny ◽  
Tamer M. Samir ◽  
Aliaa A. Ali ◽  
Amani A. El-Kholy ◽  
Ahmed S. Attia

Neonatal sepsis is a leading cause of death among newborns and infants, especially in the developing world. The problem is compounded by the delays in pinpointing the causative agent of the infection. This is reflected in increasing mortality associated with these cases and the spread of multi-drug-resistant bacteria. In this work, we deployed bioinformatics and proteomics analyses to determine a promising target that could be used for the identification of a major neonatal sepsis causative agent, Klebsiella pneumoniae. A 19 amino acid peptide from a hypothetical outer membrane was found to be very specific to the species, well conserved among its strains, surface exposed, and expressed in conditions simulating infection. Antibodies against the selected peptide were conjugated to gold nanoparticles and incorporated into an immunochromatographic strip. The developed strip was able to detect as low as 105 CFU/mL of K. pneumoniae. Regarding specificity, it showed negative results with both Escherichia coli and Enterobacter cloacae. More importantly, in a pilot study using neonatal sepsis cases blood specimens, the developed strip selectively gave positive results within 20 min with those infected with K. pneumoniae without prior sample processing. However, it gave negative results in cases infected with other bacterial species.


2015 ◽  
Vol 15 (1) ◽  
pp. 84 ◽  
Author(s):  
Sara Ghorbani-Nezami ◽  
Lucy LeBlanc ◽  
Diane G. Yost ◽  
Penny S. Amy

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4958
Author(s):  
Jessa Marie V. Makabenta ◽  
Jungmi Park ◽  
Cheng-Hsuan Li ◽  
Aritra Nath Chattopadhyay ◽  
Ahmed Nabawy ◽  
...  

Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species. The co-existence of multiple species of bacteria in biofilms exacerbates therapeutic challenges and can render traditional antibiotics ineffective. Polymeric nanoparticles offer alternative antimicrobial approaches to antibiotics, owing to their tunable physico-chemical properties. Here, we report the efficacy of poly(oxanorborneneimide) (PONI)-based antimicrobial polymeric nanoparticles (PNPs) against multi-species bacterial biofilms. PNPs showed good dual-species biofilm penetration profiles as confirmed by confocal laser scanning microscopy. Broad-spectrum antimicrobial activity was observed, with reduction in both bacterial viability and overall biofilm mass. Further, PNPs displayed minimal fibroblast toxicity and high antimicrobial activity in an in vitro co-culture model comprising fibroblast cells and dual-species biofilms of Escherichia coli and Pseudomonas aeruginosa. This study highlights a potential clinical application of the presented polymeric platform.


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