Bacteriophage therapy against Pseudomonas aeruginosa biofilms: a review

Abstract

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.

It’s Not Easy Being Green: A Narrative Review on the Microbiology, Virulence and Therapeutic Prospects of Multidrug-Resistant Pseudomonas aeruginosa

“…Additionally, it is questionable how long the new agents can manage the worsening resistance situation [146,157,[249][250][251][252][253][254]. With the daunting increase in antimicrobial resistance rates in all types of bacteria, one of the main aims of antimicrobial research is the exploration for new approaches past conventional antibiotics, such as bacteriophages, antimicrobial peptides with diverse structures and mechanisms of action, virulence inhibitors, siderophores, compounds from natural origins (like essential oils), and other adjuvants (e.g., efflux pump inhibitors, monoclonal antibodies) (Table 3) [118,[255][256][257][258][259][260][261][262][263][264][265][266][267][268][269][270]. It is possible that in the next couple of decades, these agents will play a major role in the management of serious bacterial infections caused by P. aeruginosa and other pathogens of critical importance.…”

In Vitro Newly Isolated Environmental Phage Activity against Biofilms Preformed by Pseudomonas aeruginosa from Patients with Cystic Fibrosis

“…By testing lytic phage activity in vitro, we identified five lytic phages all showing wide host range spectra against the panel of 32 CF PA isolates, namely Φ4_ZP1, Φ9_ZP2, Φ14_OBG, Φ17_OBG, and Φ19_OBG (Figure 2). When we tested in vitro the CF PA biofilms with three antibiotics chosen for their efficiency against CF PA isolates [8,16], after exposing them to phages for 4 h, only one of the five phages selected, the phage Φ4_ZP1, combined with MPM and compared with MPM alone, exhibited major lytic activity in significantly reducing two clinical CF PA biofilms (Pa_Ph10 at MOI 100, p < 0.01; Pa_Ph12 at MOI 1, p < 0.01) (Figure 4). This key unexpected finding contrasts strongly with previous evidence in phage-MPM combinations reporting no improved antimicrobial activity against various non-CF PA biofilms [17].…”

“…This biofilm lifestyle prevents antibiotics from eradicating PA, especially multidrug-resistant (MDR) PA [5]. To overcome the current lack of research on new antibiotics against MDR PA, Western countries have reappraised research on bacteriophages (phages), viruses that naturally infect bacteria [6][7][8]. Since the past century, these viruses, commonly found in the environment (sewage and dirty water), have attracted interest as a promising therapeutic alternative to antibiotics [8].…”

“…To overcome the current lack of research on new antibiotics against MDR PA, Western countries have reappraised research on bacteriophages (phages), viruses that naturally infect bacteria [6][7][8]. Since the past century, these viruses, commonly found in the environment (sewage and dirty water), have attracted interest as a promising therapeutic alternative to antibiotics [8]. In the past years, phages have shown proven efficiency also against biofilms formed by non-CF and CF PA isolates [8,9].…”

“…Since the past century, these viruses, commonly found in the environment (sewage and dirty water), have attracted interest as a promising therapeutic alternative to antibiotics [8]. In the past years, phages have shown proven efficiency also against biofilms formed by non-CF and CF PA isolates [8,9]. Promising results also come from studies on phage therapy, alone or combined with antibiotics in treating CF PA infections, in in vitro biofilm models, and lung infected animal models [8][9][10].…”