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

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.

Phage therapy for hidradenitis suppurativa: a unique challenge and possible opportunity for personalized treatment of a complex, inflammatory disease.

Phage therapy is an emerging antimicrobial treatment for critical multidrug-resistant pathogens. In this review, the specific potential and challenges of phage therapy for patients with hidradenitis suppurativa (HS) are discussed. This represents a unique challenge as HS is a chronic inflammatory disease, but presenting with acute exacerbations, which have an enormous negative impact on patient's quality of life. The therapeutic arsenal for HS has expanded in the past decade, for example, with adalimumab and several other biologicals that are currently under investigation. However, treatment of HS remains challenging for dermatologists because there are individuals who do not respond to any classes of the current treatment options when used for a first or second time. Furthermore, after several courses of treatment, a patient may lose their response to therapy, meaning long-term use is not always an option. Culturing studies and 16S ribosomal RNA profiling highlight the complex polymicrobial nature of HS lesions. Despite the detection of various bacterial species in lesion samples, several key pathogens, including Staphylococcus, Corynebacterium and Streptococcus, may be potential targets for phage therapy. Using phage therapy for the treatment of a chronic inflammatory disease could potentially provide new insights into the role of bacteria and the immune system in HS development. In addition, it is possible more details on the immunomodulatory effects of phages may come to light.