Bacteriophages are synergistic with bacterial interference for the prevention ofPseudomonas aeruginosabiofilm formation on urinary catheters

Abstract

Aims We hypothesized that pretreating urinary catheters with benign Escherichia coli HU2117 plus an anti-pseudomonal bacteriophage (ΦE2005-A) would prevent P. aeruginosa biofilm formation on catheters – a pivotal event in the pathogenesis of catheter-associated urinary tract infection (CAUTI). Methods and Results Silicone catheter segments were exposed to one of four pretreatments (sterile media; E. coli alone; phage alone; E. coli plus phage), inoculated with P. aeruginosa, then incubated up to 72 hours in human urine before rinsing and sonicating to recover adherent bacteria. P. aeruginosa adherence to catheters was almost 4 log10 units lower when pretreated with E. coli plus phage compared to no pretreatment (P < 0.001) in 24-hour experiments and more than 3 log10 units lower in 72-hour experiments (P < 0.05). Neither E. coli nor phage alone generated significant decreases. Conclusions The combination of phages with a pre-established biofilm of E. coli HU2117 was synergistic in preventing catheter colonization by P. aeruginosa. Significance and Impact of Study We describe a synergistic protection against colonization of urinary catheters by a common uropathogen. E. coli-coated catheters are in clinical trials; adding phage may offer additional benefit.

Inhibition of Biofilm Formation by T7 Bacteriophages Producing Quorum-Quenching Enzymes

“…As part of the resurrection of phage research in Western countries to solve the problem of increases in antibiotic resistance (4,48), bacteriophages which lyse host bacteria have aroused increasing interest for their potential application as antibiofilm agents (4,(8)(9)(10)(11)(12). Also, quorum quenching has been investigated as a biofilm control approach in many clinical (49,50) and industrial (23,24,51) settings, due to the essential role of quorum sensing in regulating biofilm formation.…”

“…Phages are capable of lysing host bacteria in experimental single-and mixed-species bacterial biofilms (6,7). Phages have been explored as antibiofilm agents in diverse industrial and clinical settings, including phage therapy (4), biofilm-infected medical devices (8)(9)(10)(11), and filtration membranes (12). In many biofilm systems, however, EPS still pose a challenge, limiting the bactericidal effect of phages (13,14).…”

Biofilm Models of Polymicrobial Infection

“…The investigators observed that the blanket of bacteria and phage across the catheter surface prevented P. aeruginosa adherence [34], suggesting a potential therapeutic probiotic/ phage approach to prevent CAUTI.…”

“…Antagonistic mechanisms include: production of factors that kill or inhibit the growth of neighbors, production of chemical signals that can interfere with or disrupt the behavior or physiology of neighbors, or hoarding of nutrients that starves neighbors [15,[30][31][32][33]. 'Surface blanketing' occurs when one species occupies all the attachment sites on a surface, thereby preventing the attachment of another [15,34,35]. Investigating antagonistic relationships between microbes not only provides insight into bacterial social behavior, but also may hold keys to disrupting biofilm structure and composition, potentially leading to novel treatments for biofilm-related infections.…”

Using Phage’s to Exterminate Biofilms

“…Thus, it should be put in consideration that for treating biofilms temporary by phages, it would be required that the biofilm cells surface be exposed to some disruption prior to phage application. Other combinations are also possible exactly like in the case of biological systems Liao et al [69]; noticed that combining phages with commensal bacteria had synergistic effects in preventing biofilm formation on silicone catheter segments while Zhang and Hu [70]; observed when using phages coupled with biocide like (chlorine) the effects on filters is increased. However, further studies have to target on exploring phage activity in the multispecies context, animal models, and in conjunction with other antimicrobials [71].…”