Effect of Bacteriophage Infection in Combination with  Tobramycin on the Emergence of Resistance in Escherichia coli and Pseudomonas aeruginosa Biofilms

Coulter, Lindsey Blythe; McLean, Robert; Rohde, Rodney E.; Aron, Gary M.

doi:10.3390/v6103778

Cited by 106 publications

(87 citation statements)

References 32 publications

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“…Changes in DNA replication could induce disruption of the biofilm exopolymeric matrix causing increased penetration of phage and antibiotic at higher diffusion rates. Similar mechanisms have been previously reported in the study of amikacin and phage synergism [40] as well as tobramycin (0.5 µg/ml) and 0.01 MOI phage for the treatment of established P. aeruginosa biofilms [49]. Hagens et al show that phage treatment augmented inhibition of P. aeruginosa using low doses of tetracycline [50].…”

Section: Discussionsupporting

confidence: 55%

Efficacy of Phage and Ciprofloxacin Co-therapy on the Formation and Eradication of Pseudomonas aeruginosa Biofilms

2016

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Pseudomonas aeruginosa, a gram negative, multiple drug-resistant (MDR) biofilm forming organism associated with nosocomial infections, is the causative agent of several life-threatening diseases. Emergence of multiple drug resistance against current generation antibiotics in such pathogens is a serious problem for medical practitioners. An alternative means to control the MDR pathogens is combination therapy of antibiotic with suitable biological control measures such as lytic bacteriophages. In this study, we report the isolation and characterization of P. aeruginosa specific phage vB_PaeM_P6 which is used in combination with subminimal inhibitory concentrations (MIC) of ciprofloxacin for the control of P. aeruginosa biofilm. Synergistic activity of phage 0.05 multiplicity of infection and sub-MIC ciprofloxacin (0.75 µg/ml) treatment is reported for the inhibition of biofilm forming as well as preformed biofilms of five clinical strains of P. aeruginosa.

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Section: Discussionsupporting

confidence: 55%

Efficacy of Phage and Ciprofloxacin Co-therapy on the Formation and Eradication of Pseudomonas aeruginosa Biofilms

2016

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“…Phage therapy is being considered, again, for use both in the food industry and in medicine (25). In addition, several reports showed that phage therapy improved (26)(27)(28), and in some cases was even more successful than (29,30), antibiotic treatment.…”

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confidence: 99%

Targeting Enterococcus faecalis Biofilms with Phage Therapy

Khalifa

Brosh

Gelman

et al. 2015

Appl Environ Microbiol

188

158

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Phage therapy has been proven to be more effective, in some cases, than conventional antibiotics, especially regarding multidrug-resistant biofilm infections. The objective here was to isolate an anti-Enterococcus faecalis bacteriophage and to evaluate its efficacy against planktonic and biofilm cultures. E. faecalis is an important pathogen found in many infections, including endocarditis and persistent infections associated with root canal treatment failure. The difficulty in E. faecalis treatment has been attributed to the lack of anti-infective strategies to eradicate its biofilm and to the frequent emergence of multidrug-resistant strains. To this end, an anti-E. faecalis and E. faecium phage, termed EFDG1, was isolated from sewage effluents. The phage was visualized by electron microscopy. EFDG1 coding sequences and phylogeny were determined by whole genome sequencing (GenBank accession number KP339049), revealing it belongs to the Spounavirinae subfamily of the Myoviridae phages, which includes promising candidates for therapy against Gram-positive pathogens. This analysis also showed that the EFDG1 genome does not contain apparent harmful genes. EFDG1 antibacterial efficacy was evaluated in vitro against planktonic and biofilm cultures, showing effective lytic activity against various E. faecalis and E. faecium isolates, regardless of their antibiotic resistance profile. In addition, EFDG1 efficiently prevented ex vivo E. faecalis root canal infection. These findings suggest that phage therapy using EFDG1 might be efficacious to prevent E. faecalis infection after root canal treatment.

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“…Additionally, phage-encoded proteins, such as endolysins and exopolysaccharide depolymerases, can also be used for biofilm removal (19)(20)(21). Nevertheless, most studies available to date have focused on single-species communities, while only limited work has tackled the elimination of polymicrobial biofilms with phage-based products (22)(23)(24)(25)(26).…”

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The Behavior of Staphylococcus aureus Dual-Species Biofilms Treated with Bacteriophage phiIPLA-RODI Depends on the Accompanying Microorganism

González

Fernández

Campelo

et al. 2017

Appl Environ Microbiol

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The use of bacteriophages as antimicrobials against pathogenic bacteria offers a promising alternative to traditional antibiotics and disinfectants. Significantly, phages may help to remove biofilms, which are notoriously resistant to commonly used eradication methods. However, the successful development of novel antibiofilm strategies must take into account that real-life biofilms usually consist of mixed-species populations. Within this context, this study aimed to explore the effectiveness of bacteriophage-based sanitation procedures for removing polymicrobial biofilms from food industry surfaces. We treated dual-species biofilms formed by the food pathogenic bacterium Staphylococcus aureus in combination with Lactobacillus plantarum, Enterococcus faecium, or Lactobacillus pentosus with the staphylococcal phage phiIPLA-RODI. Our results suggest that the impact of bacteriophage treatment on S. aureus mixed-species biofilms varies depending on the accompanying species and the infection conditions. For instance, short treatments (4 h) with a phage suspension under nutrient-limiting conditions reduced the number of S. aureus cells in 5-h biofilms by ϳ1 log unit without releasing the nonsusceptible species. In contrast, longer infection periods (18 h) with no nutrient limitation increased the killing of S. aureus cells by the phage (decrease of up to 2.9 log units). However, in some cases, these conditions promoted the growth of the accompanying species. For example, the L. plantarum cell count in the treated sample was up to 2.3 log units higher than that in the untreated control. Furthermore, phage propagation inside dual-species biofilms also depended greatly on the accompanying species, with the highest rate detected in biofilms formed by S. aureus-L. pentosus. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) also showed changes in the three-dimensional structures of the mixed-species biofilms after phage treatment. Altogether, the results presented here highlight the need to study the impact of phage therapy on microbial communities that reflect a more realistic setting.IMPORTANCE Biofilms represent a major source of contamination in industrial and hospital settings. Therefore, developing efficient strategies to combat bacterial biofilms is of the utmost importance from medical and economic perspectives. Bacteriophages have shown potential as novel antibiofilm agents, but further research is still required to fully understand the interactions between phages and biofilm-embedded bacteria. The results presented in this study contribute to achieving a better understanding of such interactions in a more realistic context, considering that most biofilms in the environment consist of mixed-species populations. KEYWORDS Staphylococcus aureus, biofilms, phage

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Effect of Bacteriophage Infection in Combination with Tobramycin on the Emergence of Resistance in Escherichia coli and Pseudomonas aeruginosa Biofilms

Cited by 106 publications

References 32 publications

Efficacy of Phage and Ciprofloxacin Co-therapy on the Formation and Eradication of Pseudomonas aeruginosa Biofilms

Efficacy of Phage and Ciprofloxacin Co-therapy on the Formation and Eradication of Pseudomonas aeruginosa Biofilms

Targeting Enterococcus faecalis Biofilms with Phage Therapy

The Behavior of Staphylococcus aureus Dual-Species Biofilms Treated with Bacteriophage phiIPLA-RODI Depends on the Accompanying Microorganism

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