Isolation and Characterization of ΦCA1NRNZ, a Lytic Bacteriophage Targeting the Emerging Device-Associated Pathogen Cutibacterium avidum

Background: Cutibacterium avidum is an emerging opportunistic pathogen responsible for device-associated infections, including prosthetic joint and breast implant infections. Unlike its relative C. acnes, for which phage therapy has been explored, C. avidum infections are recalcitrant to antibiotics, and no infecting bacteriophages have been described to date. Here, we report the isolation and characterization of ΦCA1NRNZ, to the best of our knowledge, the first lytic phage described against C. avidum. Methods: ΦCA1NRNZ was obtained from wastewater sampling at the Sorek Treatment Facility in Jerusalem. Wastewater metagenomics, transmission electron microscopy, genome sequencing, host-range testing, efficiency of plating (EOP), aerobic and anaerobic lysis assays, and antibiofilm assays against mature C. avidum biofilms were performed. Results: Metagenomic analysis indicated low and transient detection of C. avidum-classified reads in wastewater. ΦCA1NRNZ was identified as a long-tailed Caudoviricetes with a ~320 nm virion. Its 33,712 bp dsDNA genome (GenBank PV441878.1) encodes 46 predicted proteins, shares 76.5% nucleotide identity with C. acnes phage ΦFD1, and contains divergent tail-fiber and host-recognition genes. No known bacterial virulence, toxin, human pathogenicity-associated, or antibiotic-resistance genes were identified. ΦCA1NRNZ lysed all 11 clinical C. avidum isolates tested under aerobic and anaerobic conditions, with EOP values of 0.11–5.55, mean 1.87, and showed no lytic activity against 25 C. acnes isolates. Against mature biofilms, ΦCA1NRNZ reduced total biomass by 28.4% (p = 0.014), reduced viable cell counts by approximately two logs, and increased extracellular ATP release (p < 0.001). Conclusions: The strict species specificity and significant in vitro antibiofilm activity of ΦCA1NRNZ support its potential for phage therapy of device-associated C. avidum infections.