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

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.

SUBMITTER: da Silva JD

PROVIDER: S-EPMC10537623 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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

da Silva Jéssica Duarte JD Bens Lene L Santos Adriele J do Carmo AJDC Lavigne Rob R Soares José J Melo Luís D R LDR Vallino Marta M Dias Roberto Sousa RS Drulis-Kawa Zuzanna Z de Paula Sérgio Oliveira SO Wagemans Jeroen J

Microorganisms 20230823 9

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 ...[more]

PMID: 37763984

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Project description:Proteus mirabilis is commonly considered to be an opportunistic pathogen causing urinary tract infections (UTIs) in humans. However, some strains of P. mirabilis were found to be associated with food poisoning outbreaks, with the pathogenic mechanism still unclear. In our study, we described a novel strain of P. mirabilis C02011 isolated from patients' specimens in a food poisoning in China. In order to determine its gastrointestinal pathogenicity, experiments were performed to compare P. mirabilis B02005 strain (isolated from healthy people) and P. mirabilis American Type Culture Collection (ATCC) 29906 strain both in vitro [Caco-2 cells: bacterial adhesion and invasion assays, Giemsa staining, and transmission electron microscopy (TEM)] and in vivo [BALB/c mouse model: fecal character, colon injury, histological examination, immunochemistry, and western blotting (WB)]. According to the results, C02011 strain exhibited almost identical characteristics with B02005 strain in bacterial appearance and proliferation. In vitro, Caco-2 cells were infected with P. mirabilis C02011, B02005, and P. mirabilis ATCC 29906 strains. After that, Giemsa staining and TEM were used for observing the infection process of C02011 strain. Meanwhile, the adhesive abilities of different strains were rated as follows: P. mirabilis B02005 > P. mirabilis C02011 > P. mirabilis ATCC 29906 (P < 0.01). Invasive abilities of different strains were rated as follows: P. mirabilis C02011 > P. mirabilis B02005 > P. mirabilis ATCC 29906 (P < 0.01). In vivo, BALB/c mice were infected with P. mirabilis C02011 and B02005 strains. C02011 strain shows more virulence than B02005 strain in terms of the following indicators: (1) feces water content and fecal character; (2) colon length of mice; (3) histological examination on mouse intestine tissues; (4) ELISA for detecting TNF-α level in the colon; and (5) WB and immunohistochemistry (IHC) for detecting occludin protein expression in the colon. On the basis of these results, we firstly validated that the novel strain of P. mirabilis C02011 shows more gastrointestinal pathogenicity than the other strains isolated from a healthy individual. In addition, type IV secretion system (T4SS) was preliminarily confirmed to play an important role in the pathogenesis of diarrheal P. mirabilis isolated from the food poisoning incident.

Dataset Information

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

Publications

Isolation and Characterization of the <i>Acadevirus</i> Members BigMira and MidiMira Infecting a Highly Pathogenic <i>Proteus mirabilis</i> Strain.

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