Phages ZC01 and ZC03 require type-IV pilus for Pseudomonas aeruginosa infection and have a potential for therapeutic applications

Author(s):Show less -

Martins, Layla Farage ; dos Santos Junior, Ariosvaldo Pereira ; Nicastro, Gianlucca Goncalves ; Scheunemann, Gaby ; Angeli, Claudia Blanes ; Rossi, Fernando Pacheco Nobre ; Quaggio, Ronaldo Bento ; Palmisano, Giuseppe ; Sgro, German Gustavo ; Ishida, Kelly ; Baldini, Regina Lucia ; da Silva, Aline Maria

• Document type: Journal article
• Source: MICROBIOLOGY SPECTRUM; v. N/A, p. 17-pg., 2024-10-29.

Abstract

There has been a growing interest in bacteriophages as therapeutic agents to treat multidrug-resistant bacterial infections. The present work aimed at expanding the microbiological and molecular characterization of lytic phages ZC01 and ZC03 and investigating their efficacy in the control of Pseudomonas aeruginosa infection in an invertebrate animal model. These two phages were previously isolated from compost ing using P. aeruginosa strain PA14 as the enrichment host and had their genomes sequenced. ZC01 and ZC03 present, respectively, siphovirus and podovirus morpho types. ZC01 was recently classified into the genus Abidjanvirus, while ZC03 belongs to Zicotriavirus genus of the Schitoviridae N4-like viruses. Through proteomics analysis, we identified virion structural proteins of ZC01 and ZC03, including a large virion-associated RNA polymerase that is characteristic of N4-like viruses, some hypothetical proteins whose annotation should be changed to virion structural proteins and a putative peptidoglycan hydrolase. Phages ZC01 and ZC03 exhibit a limited yet distinct host range, with moderate to high efficiency of plating (EOP) values observed for a few P. aeruginosa clinical isolates. Phage susceptibility assays in PA14 mutant strains point to the type-IV pilus (T4P) as the primary receptor for phages ZC01 and ZC03, and the major pilin (Pil A PA14 ) is the T4P component recognized by these phages. Moreover, both phages significantly increase survival of Galleria mellonella larvae infected with PA14 strain. Taken together, these results underpin the therapeutic potential of these phages to treat infections by P. aeruginosa and lay the groundwork for a more detailed investigation of phage-bacteria-specific recognition mechanisms. (AU)

• FAPESP's process: 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center
• Grantee: Shaker Chuck Farah
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/04923-0 - SARS-CoV-2 glycosylation: a blueprint structural insight for understanding COVID-19 pathogenesis
• Grantee: Giuseppe Palmisano
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
• Grantee: Giuseppe Palmisano
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 22/11334-6 - EMU científico: acquisition of a mass spectrometry platform for the advanced characterization of protein glycosylation and structure in healthy and disease conditions
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Infrastructure Program - Scientific