Novel Phage-Derived Depolymerase with Activity against Proteus mirabilis Biofilms.

The adherence of Proteus mirabilis to the surface of urinary catheters leads to colonization and eventual blockage of the catheter lumen by unique crystalline biofilms produced by these opportunistic pathogens, making P. mirabilis one of the leading causes of catheter-associated urinary tract infections. The Proteus biofilms reduce efficiency of antibiotic-based treatment, which in turn increases the risk of antibiotic resistance development. Bacteriophages and their enzymes have recently become investigated as alternative treatment options. In this study, a novel Proteus bacteriophage (vB_PmiS_PM-CJR) was isolated from an environmental sample and fully characterized. The phage displayed depolymerase activity and the subsequent genome analysis revealed the presence of a pectate lyase domain in its tail spike protein. The protein was heterologously expressed and purified; the ability of the purified tail spike to degrade Proteus biofilms was tested. We showed that the application of the tail spike protein was able to reduce the adherence of bacterial biofilm to plastic pegs in a MBEC (minimum biofilm eradication concentration) assay and improve the survival of Galleria mellonella larvae infected with Proteus mirabilis. Our study is the first to successfully isolate and characterize a biofilm depolymerase from a Proteus phage, demonstrating the potential of this group of enzymes in treatment of Proteus infections.

Gut Check Time: Antibiotic Delivery Strategies to Reduce Antimicrobial Resistance.

Antimicrobial resistance (AMR) has developed into a huge threat to global health, and reducing it is an urgent priority for public health authorities. The importance of a healthy and balanced gut microbiome has been identified as a key protective factor against AMR development, but this can be significantly affected by antibiotic therapy, resulting in dysbiosis and reduction of taxonomic richness. The way in which antibiotics are administered could form an important part of future antimicrobial stewardship strategies, where drug delivery is ideally placed to play a key role in the fight against AMR. This review focuses on drug delivery strategies for antibiotic administration, including avoidance of the gut microbiome and targeted delivery approaches, which may reduce AMR.