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Novel Stenotrophomonas maltophilia Bacteriophage as Potential Therapeutic Agent

Affiliation
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353 Berlin, Germany
Fanaei Pirlar, Rima;
ORCID
0000-0002-2185-5724
Affiliation
Department of Biosystems, KU Leuven, Kasteelpark Arenberg 21, 3001 Leuven, Belgium
Wagemans, Jeroen;
Affiliation
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353 Berlin, Germany
Kunisch, Fabian;
ORCID
0000-0001-7377-1314
Affiliation
Department of Biosystems, KU Leuven, Kasteelpark Arenberg 21, 3001 Leuven, Belgium
Lavigne, Rob;
ORCID
0000-0002-5219-2521
Affiliation
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353 Berlin, Germany
Trampuz, Andrej;
ORCID
0000-0003-3586-6544
Affiliation
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Center for Musculoskeletal Surgery, Augustenburger Platz 1, 13353 Berlin, Germany
Gonzalez Moreno, Mercedes

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 °C–60 °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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