Multi-Drug Resistant (MDR) Pseudomonas aeruginosa is one of the most important bacterial pathogens that causes infection with a high mortality rate due to resistance to different antibiotics. This bacterium prompts extensive tissue damage with varying factors of virulence, and its biofilm production causes chronic and antibiotic-resistant infections. Therefore, due to the non-applicability of antibiotics for the destruction of P. aeruginosa biofilm, alternative approaches have been considered by researchers, and phage therapy is one of these new therapeutic solutions. Bacteriophages can be used to eradicate P. aeruginosa biofilm by destroying the extracellular matrix, increasing the permeability of antibiotics into the inner layer of biofilm, and inhibiting its formation by stopping the quorum-sensing activity. Furthermore, the combined use of bacteriophages and other compounds with anti-biofilm properties such as nanoparticles, enzymes, and natural products can be of more interest because they invade the biofilm by various mechanisms and can be more effective than the one used alone. On the other hand, the use of bacteriophages for biofilm destruction has some limitations such as limited host range, high-density biofilm, sub-populate phage resistance in biofilm, and inhibition of phage infection via quorum sensing in biofilm. Therefore, in this review, we specifically discuss the use of phage therapy for inhibition of P. aeruginosa biofilm in clinical and in vitro studies to identify different aspects of this treatment for broader use.

/pdf/bacteriophage-therapy-against-pseudomonas-aeruginosa-40xpp1grkm.pdf

Bacteriophage therapy against Pseudomonas aeruginosa biofilms: a review.

Biofilms are complex microbial microcolonies consisting of planktonic and dormant bacteria bound to a surface. The bacterial cells within the biofilm are embedded within the extracellular polymeric substance (EPS) consisting mainly of exopolysaccharides, secreted proteins, lipids, and extracellular DNA. This structural matrix poses a major challenge against common treatment options due to its extensive antibiotic-resistant properties. Because biofilms are so recalcitrant to antibiotics, they pose a unique challenge to patients in a nosocomial setting, mainly linked to lower respiratory, urinary tract, and surgical wound infections as well as the medical devices used during treatment. Another unique property of biofilm is its ability to adhere to both biological and man-made surfaces, allowing growth on human tissues and organs, hospital tools, and medical devices, etc. Based on prior understanding of bacteriophage structure, mechanisms, and its effects on bacteria eradication, leading research has been conducted on the effects of phages and its individual proteins on biofilm and its role in overall biofilm removal while also revealing the obstacles this form of treatment currently have. The expansion in the phage host-species range is one that urges for improvement and is the focus for future studies. This review aims to demonstrate the advantages and challenges of bacteriophage and its components on biofilm removal, as well as potential usage of phage cocktail, combination therapy, and genetically modified phages in a clinical setting.

/pdf/bacteriophage-mediated-control-of-biofilm-a-promising-new-2xcxgff2.pdf

Bacteriophage-Mediated Control of Biofilm: A Promising New Dawn for the Future

Strong biofilm-forming Enterococcus feacalis urinary tract pathogens (n = 35) were used to determine the lytic spectrum of six bacteriophages isolated from sewage samples. Only 17 Enterococcus feacalis isolates gave lytic zones with the tested bacteriophages from which five isolates were susceptible to all of them. The isolated enterococcal phages are characterized by wide range of thermal (30-90 °C) and pH (3-10) stability. They belong to order Caudovirales, from which four bacteriophages (EPA, EPB, EPD, EPF) belong to family Myoviridae and two (EPC, EPE) belong to family Siphoviridae. In addition, they have promising antibiofilm activity against the tested strong-forming biofilm E. faecalis isolates. The enterococcal phages reduced the formed and preformed biofilms to a range of 38.02-45.7% and 71.0-80.0%, respectively, as compared to the control. The same promising activities were obtained on studying the anti-adherent effect of the tested bacteriophages on the adherence of bacterial cells to the surface of urinary catheter segments. They reduced the number of adherent cells to a range of 30.8-43.8% and eradicated the pre-adherent cells to a range of 48.2-71.1%, as compared to the control. Overall, the obtained promising antibiofilm activity makes these phages good candidates for application in preventing and treating biofilm associated Enterococcus faecalis infections. 

/pdf/characterization-and-anti-biofilm-activity-of-bacteriophages-im0ac5tg.pdf

Characterization and anti-biofilm activity of bacteriophages against urinary tract Enterococcus faecalis isolates

Biochemical and genomic characterization of a novel bacteriophage BUCT555 lysing Stenotrophomonas maltophilia

Abstract Pseudomonas aeruginosa is an important pathogen that causes serious infections. Bacterial biofilms are highly resistant and render bacterial treatment very difficult, therefore necessitates alternative antibacterial strategies. Phage therapy has been recently regarded as a potential therapeutic option for treatment of bacterial infections. In the current study, a novel podovirus vB_PaeP_PS28 has been isolated from sewage with higher lytic activity against P. aeruginosa . Isolated phage exhibits a short latent period, large burst size and higher stability over a wide range of temperatures and pH. The genome of vB_PaeP_PS28 consists of 72,283 bp circular double-stranded DNA, with G + C content of 54.75%. The phage genome contains 94 open reading frames (ORFs); 32 for known functional proteins and 62 for hypothetical proteins and no tRNA genes. The phage vB_PaeP_PS28 effectively inhibited the growth of P. aeruginosa planktonic cells and displayed a higher biofilm degrading capability. Moreover, therapeutic efficacy of isolated phage was evaluated in vivo using mice infection model. Interestingly, survival of mice infected with P. aeruginosa was significantly enhanced upon treatment with vB_PaeP_PS28. Furthermore, the bacterial load in liver and kidney isolated from mice infected with P. aeruginosa and treated with phage markedly decreased as compared with phage-untreated P. aeruginosa -infected mice. These findings support the efficacy of isolated phage vB_PaeP_PS28 in reducing P. aeruginosa colonization and pathogenesis in host. Importantly, the isolated phage vB_PaeP_PS28 could be applied alone or as combination therapy with other lytic phages as phage cocktail therapy or with antibiotics to limit infections caused by P. aeruginosa . 

Isolation of a bacteriophage targeting Pseudomonas aeruginosa and exhibits a promising in vivo efficacy

Isolation and characterization of bacteriophage to control multidrug-resistant Pseudomonas aeruginosa planktonic cells and biofilm.

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Isolation and characterization of bacteriophage to control multidrug-resistant Pseudomonas aeruginosa planktonic cells and biofilm.