Isolation and Characterization of the Acadevirus Members BigMira and MidiMira Infecting a Highly Pathogenic Proteus mirabilis Strain

Jéssica Duarte da Silva; Lene Bens; Adriele J do Carmo Santos; Rob Lavigne; José Soares; Luís D R Melo; Marta Vallino; Roberto Sousa Dias; Zuzanna Drulis-Kawa; Sérgio Oliveira de Paula; Jeroen Wagemans

doi:10.3390/microorganisms11092141

Isolation and Characterization of the Acadevirus Members BigMira and MidiMira Infecting a Highly Pathogenic Proteus mirabilis Strain

Microorganisms. 2023 Aug 23;11(9):2141. doi: 10.3390/microorganisms11092141.

Authors

Affiliations

¹ Laboratory of Molecular Immunovirology, Department of Microbiology, Federal University of Viçosa, Viçosa 36570-900, MG, Brazil.
² Laboratory of Gene Technology, Department of Biosystems, Division of Animal and Human Health Engineering, KU Leuven, 3000 Leuven, Belgium.
³ Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal.
⁴ LABBELS-Associate Laboratory, 4710-057 Braga, Portugal.
⁵ Institute for Sustainable Plant Protection, National Research Council of Italy, 10135 Torino, Italy.
⁶ Department of General Biology, Federal University of Viçosa, Viçosa 36570-900, MG, Brazil.
⁷ Department of Pathogen Biology and Immunology, University of Wroclaw, 50-335 Wroclaw, Poland.

Abstract

Proteus mirabilis is an opportunistic pathogen and is responsible for more than 40% of all cases of catheter-associated urinary tract infections (CAUTIs). Healthcare-associated infections have been aggravated by the constant emergence of antibiotic-resistant bacterial strains. Because of this, the use of phages to combat bacterial infections gained renewed interest. In this study, we describe the biological and genomic features of two P. mirabilis phages, named BigMira and MidiMira. These phages belong to the Acadevirus genus (family Autographiviridae). BigMira and MidiMira are highly similar, differing only in four missense mutations in their phage tail fiber. These mutations are sufficient to impact the phages' depolymerase activity. Subsequently, the comparative genomic analysis of ten clinical P. mirabilis strains revealed differences in their antibiotic resistance profiles and lipopolysaccharide locus, with the latter potentially explaining the host range data of the phages. The massive presence of antimicrobial resistance genes, especially in the phages' isolation strain P. mirabilis MCS, highlights the challenges in treating infections caused by multidrug-resistant bacteria. The findings reinforce BigMira and MidiMira phages as candidates for phage therapy purposes.

Keywords: Acadevirus; CAUTI; Proteus mirabilis; depolymerases; podoviruses.

Grants and funding

ZDK was supported by the National Science Centre, Poland (grant UMO-2017/26/M/NZ1/00233). LDRM was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and through the Scientific Employment Stimulus Program (2021.00221.CEECIND).