scholarly journals Targeting antibiotic resistant bacteria with phages reduces bacterial density in an insect host

2018 ◽  
Author(s):  
Lauri Mikonranta ◽  
Angus Buckling ◽  
Matti Jalasvuori ◽  
Ben Raymond
Keyword(s):  
Antibiotic Resistance ◽  
Phage Therapy ◽  
Synergistic Effects ◽  
Low Frequency ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Model Studies ◽  
Evolution Of Resistance ◽  
Insect Gut

Phage therapy is attracting growing interest among clinicians as antibiotic resistance continues becoming harder to control. However, clinical trials and animal model studies on bacteriophage treatment are still scarce and results on the efficacy vary. Recent research suggests that using traditional antimicrobials in concert with phage could have desirable synergistic effects that hinder the evolution of resistance. Here, we present a novel insect gut model to study phage-antibiotic interaction in a system where antibiotic resistance initially exists in very low frequency and phage specifically targets the resistance bearing cells. We demonstrate that while phage therapy could not reduce the frequency of target bacteria in the population during positive selection by antibiotics, it alleviated the antibiotic induced blooming by lowering the overall load of resistant cells. The highly structured gut environment had pharmacokinetic effects on both phage and antibiotic dynamics compared to in vitro: antibiotics did not reduce the overall amount of bacteria, demonstrating a simple turnover of gut flora from non-resistant to resistant population with little cost. The results imply moderate potential for using phage as an aid to target antibiotic resistant gut infections, and question the usefulness of in vitro inferences.

scholarly journals Targeting antibiotic resistant bacteria with phage reduces bacterial density in an insect host

2019 ◽  
Vol 15 (3) ◽  
pp. 20180895 ◽  
Author(s):  
Lauri Mikonranta ◽  
Angus Buckling ◽  
Matti Jalasvuori ◽  
Ben Raymond
Keyword(s):  
Antibiotic Resistance ◽  
Phage Therapy ◽  
Synergistic Effects ◽  
Low Frequency ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Model Studies ◽  
Evolution Of Resistance ◽  
Insect Gut

Phage therapy is attracting growing interest among clinicians as antibiotic resistance continues becoming harder to control. However, clinical trials and animal model studies on bacteriophage treatment are still scarce and results on the efficacy vary. Recent research suggests that using traditional antimicrobials in concert with phage could have desirable synergistic effects that hinder the evolution of resistance. Here, we present a novel insect gut model to study phage–antibiotic interaction in a system where antibiotic resistance initially exists in very low frequency and phage specifically targets the resistance bearing cells. We demonstrate that while phage therapy could not reduce the frequency of target bacteria in the population during positive selection by antibiotics, it alleviated the antibiotic induced blooming by lowering the overall load of resistant cells. The highly structured gut environment had pharmacokinetic effects on both phage and antibiotic dynamics compared with in vitro : antibiotics did not reduce the overall amount of bacteria, demonstrating a simple turnover of gut microbiota from non-resistant to resistant population with little cost. The results imply moderate potential for using phage as an aid to target antibiotic resistant gut infections, and question the usefulness of in vitro inferences.

The Activity of Alkanna Species in vitro Culture and Intact Plant Extracts Against Antibiotic Resistant Bacteria

2019 ◽  
Vol 25 (16) ◽  
pp. 1861-1865 ◽  
Author(s):  
Naira Sahakyan ◽  
Margarit Petrosyan ◽  
Armen Trchounian
Keyword(s):  
Antibiotic Resistance ◽  
Antibacterial Agents ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Resistant Bacteria ◽  
Plant Origin ◽  
Bacterial Strains ◽  
Biotechnological Production ◽  
Antibiotic Resistant

Overcoming the antibiotic resistance is nowadays a challenge. There is still no clear strategy to combat this problem. Therefore, the urgent need to find new sources of antibacterial agents exists. According to some literature, substances of plant origin are able to overcome bacterial resistance against antibiotics. Alkanna species plants are among the valuable producers of these metabolites. But there is a problem of obtaining the standardized product. So, this review is focused on the discussion of the possibilities of biotechnological production of antimicrobial agents from Alkanna genus species against some microorganisms including antibiotic resistant bacterial strains.

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.

scholarly journals Coevolutionary phage training leads to greater bacterial suppression and delays the evolution of phage resistance

2020 ◽  
Author(s):  
Joshua M. Borin ◽  
Sarit Avrani ◽  
Jeffrey E. Barrick ◽  
Katherine L. Petrie ◽  
Justin R. Meyer
Keyword(s):  
Phage Therapy ◽  
Single Step ◽  
Resistant Bacteria ◽  
Phage Resistance ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Major Barrier ◽  
Complete Resistance ◽  
Transfer Of Information

AbstractThe evolution of antibiotic resistant bacteria threatens to become the leading cause of worldwide mortality. This crisis has renewed interest in the practice of phage therapy. Yet, bacteria’s capacity to evolve resistance is likely to debilitate this therapy as well. To combat the evolution of phage resistance and improve treatment outcomes, many have suggested leveraging phages’ ability to counter resistance by evolving phages on target hosts before using them in therapy (phage training). We found that during in vitro experiments, a phage trained for 28 days suppressed bacteria ∼1000-fold for 3-8 times longer than its untrained ancestor. This extension was due to a delay in the evolution of resistance. Several factors contributed to this prolonged suppression. Mutations that confer resistance to trained phages are ∼100× less common and, while the target bacterium can evolve complete resistance to the untrained phage in a single step, multiple mutations are required to evolve complete resistance to trained phages. Mutations that confer resistance to trained phages are more costly than mutations for untrained phage resistance. And when resistance does evolve, trained phages are better able to suppress these forms of resistance. One way the trained phage improved was through recombination with a gene in a defunct prophage in the host genome, which doubled phage fitness. This direct transfer of information encoded by the host but originating from a relict phage provides a previously unconsidered mode of training phage. Overall, we provide a case study for successful phage training and uncover mechanisms underlying its efficacy.Significance StatementThe evolution of antibiotic resistant bacteria threatens to claim over 10 million lives annually by 2050. This crisis has renewed interest in phage therapy, the use of bacterial viruses to treat infections. A major barrier to successful phage therapy is that bacteria readily evolve phage resistance. One idea proposed to combat resistance is “training” phages by using their natural capacity to evolve to counter resistance. Here, we show that training phages by coevolving them with their host for one month enhanced their capacity for suppressing bacterial growth and delayed the emergence of resistance. Enhanced suppression was caused by several mechanisms, suggesting that the coevolutionary training protocol produces a robust therapeutic that employs complementary modes of action.

scholarly journals Bacteriophage selection against a plasmid-encoded sex apparatus leads to the loss of antibiotic-resistance plasmids

2011 ◽  
Vol 7 (6) ◽  
pp. 902-905 ◽  
Author(s):  
Matti Jalasvuori ◽  
Ville-Petri Friman ◽  
Anne Nieminen ◽  
Jaana K. H. Bamford ◽  
Angus Buckling
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Bacterial Species ◽  
Low Frequency ◽  
Antibiotic Resistance Genes ◽  
Resistant Bacteria ◽  
Bacterial Cells ◽  
Antibiotic Resistant ◽  
Resistance Plasmids ◽  
Resistant Mutants

Antibiotic-resistance genes are often carried by conjugative plasmids, which spread within and between bacterial species. It has long been recognized that some viruses of bacteria (bacteriophage; phage) have evolved to infect and kill plasmid-harbouring cells. This raises a question: can phages cause the loss of plasmid-associated antibiotic resistance by selecting for plasmid-free bacteria, or can bacteria or plasmids evolve resistance to phages in other ways? Here, we show that multiple antibiotic-resistance genes containing plasmids are stably maintained in both Escherichia coli and Salmonella enterica in the absence of phages, while plasmid-dependent phage PRD1 causes a dramatic reduction in the frequency of antibiotic-resistant bacteria. The loss of antibiotic resistance in cells initially harbouring RP4 plasmid was shown to result from evolution of phage resistance where bacterial cells expelled their plasmid (and hence the suitable receptor for phages). Phages also selected for a low frequency of plasmid-containing, phage-resistant bacteria, presumably as a result of modification of the plasmid-encoded receptor. However, these double-resistant mutants had a growth cost compared with phage-resistant but antibiotic-susceptible mutants and were unable to conjugate. These results suggest that bacteriophages could play a significant role in restricting the spread of plasmid-encoded antibiotic resistance.

Phage Therapy: A Potential Solution for Antibiotic Resistance

2021 ◽  
Author(s):  
Chirag Choudhary ◽  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Biological Agents ◽  
Resistant Bacteria ◽  
Potential Solution ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
The Future

The idea of using a virus to kill bacteria may seem counterintuitive, but it may be the future of treating bacterial infections. Before the COVID-19 pandemic, one of the most frightening biological agents were so-called “superbugs” – antibiotic resistant bacteria – which could not be treated with conventional therapeutics. When antibiotics were first developed, they were hailed as a panacea. A panacea they were not.

scholarly journals A trimethoprim derivative impedes antibiotic resistance evolution

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Madhu Sudan Manna ◽  
Yusuf Talha Tamer ◽  
Ilona Gaszek ◽  
Nicole Poulides ◽  
Ayesha Ahmed ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistant Bacteria ◽  
Gene Encoding ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Resistance Evolution ◽  
Evolutionary Trajectories ◽  
Evolution Of Resistance

AbstractThe antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory evolution experiments have identified resistance-conferring mutations in the gene encoding the TMP target, bacterial dihydrofolate reductase (DHFR), in particular mutation L28R. Here, we show that 4’-desmethyltrimethoprim (4’-DTMP) inhibits both DHFR and its L28R variant, and selects against the emergence of TMP-resistant bacteria that carry the L28R mutation in laboratory experiments. Furthermore, antibiotic-sensitive E. coli populations acquire antibiotic resistance at a substantially slower rate when grown in the presence of 4’-DTMP than in the presence of TMP. We find that 4’-DTMP impedes evolution of resistance by selecting against resistant genotypes with the L28R mutation and diverting genetic trajectories to other resistance-conferring DHFR mutations with catalytic deficiencies. Our results demonstrate how a detailed characterization of resistance-conferring mutations in a target enzyme can help identify potential drugs against antibiotic-resistant bacteria, which may ultimately increase long-term efficacy of antimicrobial therapies by modulating evolutionary trajectories that lead to resistance.

scholarly journals THE POSSIBILITIES OF USING PHAGE THERAPY IN DENTISTRY

2018 ◽  
Vol 22 (2) ◽  
pp. 107-110
Author(s):  
Maria Vladimirovna Kuchmina ◽  
A. Yu Turkina ◽  
Yu. O Paramonov
Keyword(s):  
Bacterial Cell ◽  
Phage Therapy ◽  
Periodontal Diseases ◽  
Resistant Bacteria ◽  
Clinical Use ◽  
Antibiotic Resistant ◽  
Domestic Literature ◽  
Advantages And Disadvantages

The article is devoted to the possibilities of using bacteriophages in dentistry. The main characteristics of bacteriophages and mechanisms of their interaction with a bacterial cell as well as the data of microbiological studies and the results of clinical use of bacteriophages in periodontal diseases are discussed. Bacteriophages have been shown to be effective against periodontopathogenic microorganisms, including antibiotic resistant bacteria in vitro and in vivo. There were reflected the advantages and disadvantages of phage therapy, the main of which for today is a small experience of clinical use of this method. Objective. To analyze the data of foreign and domestic literature and publications in the field of phagotherapy effectiveness in dentistry.

scholarly journals Evaluation of Phage Therapy in the Context of Enterococcus faecalis and Its Associated Diseases

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 366 ◽  
Author(s):  
Bolocan ◽  
Upadrasta ◽  
Bettio ◽  
Clooney ◽  
Draper ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Antimicrobial Agents ◽  
Phage Therapy ◽  
Domain Architecture ◽  
The Body ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Antibiotic Resistant

Bacteriophages (phages) or bacterial viruses have been proposed as natural antimicrobial agents to fight against antibiotic-resistant bacteria associated with human infections. Enterococcus faecalis is a gut commensal, which is occasionally found in the mouth and vaginal tract, and does not usually cause clinical problems. However, it can spread to other areas of the body and cause life-threatening infections, such as septicemia, endocarditis, or meningitis, in immunocompromised hosts. Although E. faecalis phage cocktails are not commercially available within the EU or USA, there is an accumulated evidence from in vitro and in vivo studies that have shown phage efficacy, which supports the idea of applying phage therapy to overcome infections associated with E. faecalis. In this review, we discuss the potency of bacteriophages in controlling E. faecalis, in both in vitro and in vivo scenarios. E. faecalis associated bacteriophages were compared at the genome level and an attempt was made to categorize phages with respect to their suitability for therapeutic application, using orthocluster analysis. In addition, E. faecalis phages have been examined for the presence of antibiotic-resistant genes, to ensure their safe use in clinical conditions. Finally, the domain architecture of E. faecalis phage-encoded endolysins are discussed.

scholarly journals Antibiotic resistance in surface waters from a coastal lagoon of Southern Brazil under the impact of anthropogenic activities

2019 ◽  
Vol 14 (5) ◽  
pp. 1
Author(s):  
Belize Leite ◽  
Magda Antunes de Chaves ◽  
Athos Aramis Thopor Nunes ◽  
Louise Jank ◽  
Gertrudes Corção
Keyword(s):  
Antibiotic Resistance ◽  
Coastal Lagoon ◽  
Anthropogenic Activities ◽  
Class I ◽  
Systematic Evaluation ◽  
Resistant Bacteria ◽  
Bacterial Populations ◽  
Antibiotic Resistant ◽  
The Impact

Wastes arising from human activities can reach water bodies and contribute significantly to the presence of antibiotic resistant bacterial populations in aquatic environments. The objective of this study was to evaluate the cultivable antibiotic resistant bacterial populations from a coastal lagoon impacted by agriculture and urbanization activities. Water samples were collected in low and peak season and characterized regarding physicochemical variables, microbiological indicators and the presence of antimicrobial residues. In order to analyze the presence of resistant bacterial populations, the samples were grown in the presence of nalidixic acid, ceftazidime, imipenem and tetracycline. Genes associated with β-lactamic resistance (blaCTX-M-like, blaGES-like, blaOXA-51, blaOXA-23-like, blaSHV-like, blaTEM-like and blaSPM-1), class I integron and efflux systems (tetA, tetB, acrA, acrB, tolC, adeA, adeB, adeR, adeS, mexB, mexD, mexF and mexY) were analyzed by conventional in vitro amplification. Although antimicrobials residues were below the detection limit, resistant bacteria and resistance determinants - blaGES, class I integron, adeS, acrA, acrB, tolC, mexB, mexF - were present at almost all points, in both seasons and for all antimicrobials assessed. The high numbers of resistant bacteria counts observed after the antibiotic treatment were positively correlated to the urbanization effects on the Lagoon. Some resistant populations were even higher in the low season samples, indicating the importance of a systematic evaluation of antibiotic resistance on water resources.

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