Evaluation of the activity of a combination of three #bacteriophages alone or in association with #antibiotics on #Staphylococcus aureus embedded in #biofilm or internalised in #osteoblasts (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Evaluation of the activity of a combination of three bacteriophages alone or in association with antibiotics on Staphylococcus aureus embedded in biofilm or internalised in osteoblasts

Camille Kolenda, Jérôme Josse, Mathieu Medina, Cindy Fevre, Sébastien Lustig, Tristan Ferry, Frédéric Laurent

DOI: 10.1128/AAC.02231-19

 

ABSTRACT

Background:

Staphylococcus aureus is responsible for difficult-to-treat bone and joint infections (BJIs). This is related to its ability to form biofilm, and to be internalised and persist inside osteoblasts. Recently, bacteriophage therapy has emerged as a promising option to improve treatment of such infections but data on its activity against the specific bacterial lifestyles presented above remain scarce.

Methods:

We evaluated the activity of a combination of three bacteriophages, recently used for compassionate treatment in France, against S. aureus HG001 in a model of staphylococcal biofilm and a model of osteoblasts infection, alone or in association with vancomycin or rifampicin.

Results:

The activity of bacteriophages against biofilm-embedded S. aureus was dose-dependent. In addition, synergistic effects were observed when bacteriophages were combined with antibiotics used at the lowest concentrations. Phage penetration into osteoblasts was observed only when the cells were infected, suggesting a S. aureus-dependent Trojan horse mechanism for internalisation. The intracellular bacterial count of bacteria in infected osteoblasts treated with bacteriophages, as well as with vancomycin, was significantly higher than in cells treated with lysostaphin, used as control condition, owing to the absence of intracellular activity, and the rapid killing of bacteria released after death of infected cells. These results suggest that bacteriophages are both inactive in the intracellular compartment after being internalised in infected osteoblasts, and present a delayed killing effect on bacteria released after cell lysis into the extracellular compartment which avoid to prevent them from infecting other osteoblasts.

Conclusion:

The combination of bacteriophages tested was highly active against S. aureus embedded in biofilm but showed no activity against intracellular bacteria in the cell model used.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; Bacteriophages.

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#Bacteriophage Adherence to #Mucus Mediates Preventive #Protection against Pathogenic #Bacteria (MBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Bacteriophage Adherence to Mucus Mediates Preventive Protection against Pathogenic Bacteria

Gabriel M. F. Almeida, Elina Laanto, Roghaieh Ashrafi, Lotta-Riina Sundberg

Jennifer B. H. Martiny, Editor

DOI: 10.1128/mBio.01984-19

 

ABSTRACT

Metazoans were proposed to host bacteriophages on their mucosal surfaces in a symbiotic relationship, where phages provide an external immunity against bacterial infections and the metazoans provide phages a medium for interacting with bacteria. However, scarce empirical evidence and model systems have left the phage-mucus interaction poorly understood. Here, we show that phages bind both to porcine mucus and to rainbow trout (Oncorhynchus mykiss) primary mucus, persist up to 7 days in the mucosa, and provide protection against Flavobacterium columnare. Also, exposure to mucus changes the bacterial phenotype by increasing bacterial virulence and susceptibility to phage infections. This trade-off in bacterial virulence reveals ecological benefit of maintaining phages in the metazoan mucosal surfaces. Tests using other phage-bacterium pairs suggest that phage binding to mucus may be widespread in the biosphere, indicating its importance for disease, ecology, and evolution. This phenomenon may have significant potential to be exploited in preventive phage therapy.

 

IMPORTANCE

The mucosal surfaces of animals are habitat for microbes, including viruses. Bacteriophages—viruses that infect bacteria—were shown to be able to bind to mucus. This may result in a symbiotic relationship in which phages find bacterial hosts to infect, protecting the mucus-producing animal from bacterial infections in the process. Here, we studied phage binding on mucus and the effect of mucin on phage-bacterium interactions. The significance of our research is in showing that phage adhesion to mucus results in preventive protection against bacterial infections, which will serve as basis for the development of prophylactic phage therapy approaches. Besides, we also reveal that exposure to mucus upregulates bacterial virulence and that this is exploited by phages for infection, adding one additional layer to the metazoan-bacterium-phage biological interactions and ecology. This phenomenon might be widespread in the biosphere and thus crucial for understanding mucosal diseases, their outcome and treatment.

Keywords: Bacteriophages.

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Efficacy of #bacteriophages in a S. aureus non-diabetic or #diabetic #foot #infection murine model (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Efficacy of bacteriophages in a S. aureus non-diabetic or diabetic foot infection murine model

S. Albac, M. Medina, D. Labrousse, D. Hayez, D. Bonnot, N. Anzala, F. Laurent, T. Ferry, A. Dublanchet, P. Chavanet, C. Fevre, D. Croisier

DOI: 10.1128/AAC.01870-19

 

ABSTRACT

This study investigated the in vivo efficiency of three combined bacteriophages compared to linezolid, in two mouse models (non-diabetic or diabetic) of S. aureus foot infection. In both models, a single injection of bacteriophages showed a significant antibacterial efficacy in the hindpaw. Linezolid was as effective as bacteriophages in non-diabetic animals but ineffective in diabetic animals. These findings support further preclinical and clinical studies for the development of phage therapy.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Staphylococcus aureus; Diabetes; Bacteriophages.

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What’s Old is New Again – #Bacteriophage Therapy in the 21st century (Antimicrob Agents Chemother., summary)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Summary, edited.]

What’s Old is New Again – Bacteriophage Therapy in the 21st century

Saima Aslam, Robert T. Schooley

DOI: 10.1128/AAC.01987-19

 

ABSTRACT

We highlight features associated with bacteriophage therapy that make it an attractive treatment option for multi-drug resistant infections and also discuss some of the challenges that need to be considered in the design and execution of clinical trials directed at evaluating the efficacy of bacteriophage therapy in humans.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Bacteriophages.

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Successful #treatment of chronic relapsing #UTI with #bacteriophages in a renal transplant recipient – a Dutch case report (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Successful treatment of chronic relapsing urinary tract infection with bacteriophages in a renal transplant recipient – a Dutch case report

Saskia Kuipers, Mike M Ruth, Mike Mientjes, Ruud G. L. de Sévaux, Jakko van Ingen

DOI: 10.1128/AAC.01281-19

 

ABSTRACT

We report a case of a 58-year old renal transplant patient who developed recurrent urinary tract infection with an ESBL-positive Klebsiella pneumoniae strain in the first month post-transplant. Even though carbapenems tested susceptible and despite repeated meropenem treatment, his infection recurred. The infection eventually evolved into epididymitis that was successfully treated with meropenem and bacteriophages. This case demonstrates the difficulty of treating relapsing ESBL-positive Gram-negative infections in renal transplant patients.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Klebsiella pneumoniae; Bacteriophages.

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Transposable temperate #phages promote the #evolution of divergent social strategies in #Pseudomonas aeruginosa populations (Proc Roy Soc B., abstract)

[Source: Proceedings of the Royal Society, Biological Sciences, full page: (LINK). Abstract, edited.]

Transposable temperate phages promote the evolution of divergent social strategies in Pseudomonas aeruginosa populations

Siobhán O’Brien, Rolf Kümmerli, Steve Paterson, Craig Winstanley and Michael A. Brockhurst

Published: 09 October 2019 / DOI: https://doi.org/10.1098/rspb.2019.1794

 

Abstract

Transposable temperate phages randomly insert into bacterial genomes, providing increased supply and altered spectra of mutations available to selection, thus opening alternative evolutionary trajectories. Transposable phages accelerate bacterial adaptation to new environments, but their effect on adaptation to the social environment is unclear. Using experimental evolution of Pseudomonas aeruginosa in iron-limited and iron-rich environments, where the cost of producing cooperative iron-chelating siderophores is high and low, respectively, we show that transposable phages promote divergence into extreme siderophore production phenotypes. Iron-limited populations with transposable phages evolved siderophore overproducing clones alongside siderophore non-producing cheats. Low siderophore production was associated with parallel mutations in pvd genes, encoding pyoverdine biosynthesis, and pqs genes, encoding quinolone signalling, while high siderophore production was associated with parallel mutations in phenazine-associated gene clusters. Notably, some of these parallel mutations were caused by phage insertional inactivation. These data suggest that transposable phages, which are widespread in microbial communities, can mediate the evolutionary divergence of social strategies.

 

Footnotes

Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.4674518

Keywords: Bacteriophages; Evolution; Pseudomonas aeruginosa.

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#Colistin #resistance-mediated #bacterial surface #modification sensitizes #phage infection (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Colistin-resistance-mediated bacterial surface modification sensitizes phage infection

Guijuan Hao, Annie I. Chen, Ming Liu, Haijian Zhou, Marisa Egan, Xiaoman Yang, Biao Kan, Hui Wang, Mark Goulian, Jun Zhu

DOI: 10.1128/AAC.01609-19

 

ABSTRACT

Colistin is a drug of last resort for the treatment of many multidrug resistant Gram-negative bacteria, including Klebsiella pneumoniae. However, bacteria readily acquire resistance to this antibiotic via lipopolysaccharide modifications caused by spontaneous mutations or from enzymes acquired by lateral gene transfer. The fitness cost associated with these modifications remains poorly understood. In this study, we show that colistin-resistant K. pneumoniae are more susceptible to killing by a newly isolated lytic phage than the colistin sensitive parent strain. We observe this behavior for colistin-resistance conferred by a horizontally transferred mcr-1 containing plasmid and also from the inactivation of the chromosomal gene mgrB. By measuring zeta potentials, we found that the phage particles were negatively charged at neutral pH and that colistin-resistant bacteria had less negative zeta potentials than did wildtype. These results suggest that the decreased negative surface charge of colistin-resistant cells lowers the electrostatic repulsion between the phage and bacteria, thereby promoting phage adherence and subsequent infection. To further explore this, we tested the effect of phage treatment on K. pneumoniae growing in several different environments. We found that colistin-resistant cells were more susceptible to phage than were the wildtype cells when growing in biofilms or infected moth larvae and when colonizing the mammalian gut. A better understanding of these fitness costs may lead to new treatment approaches that minimize the emergence and spread of colistin-resistant pathogens in human and environmental reservoirs.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Colistin; MCR1; Klebsiella pneumoniae; Bacteriophages.

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