4.7 Article

Novel Stenotrophomonas maltophilia Bacteriophage as Potential Therapeutic Agent

Journal

PHARMACEUTICS
Volume 14, Issue 10, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics14102216

Keywords

Stenotrophomonas maltophilia; antibiotic resistance; biofilm-associated infection; bacteriophage-antibiotic combination; isothermal microcalorimetry

Funding

  1. JPIAMR: Cross-border research project ANTIBIOLAB [40AR40_185917]
  2. PRO-IMPLANT Foundation
  3. Open Access Publication Fund of Charite-Universitatsmedizin Berlin
  4. German Research Foundation (DFG)
  5. Swiss National Science Foundation (SNF) [40AR40_185917] Funding Source: Swiss National Science Foundation (SNF)

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CUB19 is a novel bacteriophage that specifically targets the bacterial species Stenotrophomonas maltophilia. It exhibits stability over a wide range of temperatures and pH values and has potent antimicrobial and antibiofilm activity. The study also suggests that CUB19 is effective when co-administered with antibiotics, making it a promising targeted therapeutic agent against biofilm-associated Stenotrophomonas infections.
A novel bacteriophage CUB19 specific to the bacterial species Stenotrophomonas maltophilia was isolated from hospital sewage and characterized as a new species belonging to a proposed new phage genus 'Cubvirus' (Caudoviricetes). Its genome contains a total of 48,301 bp and 79 predicted genes, among which some have been associated with packaging and lysis-associated proteins, structural proteins, or DNA- and metabolism-associated proteins. No lysogeny-associated proteins or known virulence proteins were identified on the phage genome. CUB19 showed stability over a wide range of temperatures (-20 degrees C-60 degrees C) and pH values (pH 3-pH 13). Despite its narrow host range, this phage has potent observed antimicrobial and antibiofilm activity. A time-killing curve assay showed significant biofilm reduction after 24 h exposure to CUP19. Isothermal microcalorimetry assays investigating phage-antibiotic combinations revealed the effectiveness of CUB19 during co-administration with increasing antibiotic doses, regardless of the administration approach (simultaneous or staggered). These are encouraging indications for its application as a targeted therapeutic agent against resilient biofilm-associated Stenotrophomonas infections.

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