Affiliations 

  • 1 Winogradsky Institute of Microbiology, RC Biotechnology RAS, Prospekt 60-Letiya Oktyabrya 7 Bld. 2, 117312 Moscow, Russia
  • 2 Department of Urology, Russian University of Medicine (ROSUNIMED), 2nd Botkinsky Proezd, 5 Bldg 20, 125284 Moscow, Russia
  • 3 Research and Production Center "MicroMir", Nizhny Kiselny Lane 5/23 Bldg 1, 107031 Moscow, Russia
  • 4 Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Malaya Pirogovskaya ul. 1a, 119435 Moscow, Russia
Int J Mol Sci, 2024 Nov 27;25(23).
PMID: 39684465 DOI: 10.3390/ijms252312755

Abstract

Escherichia coli and its bacteriophages are among the most studied model microorganisms. Bacteriophages for various E. coli strains can typically be easily isolated from environmental sources, and many of these viruses can be harnessed to combat E. coli infections in humans and animals. However, some relatively rare E. coli strains pose significant challenges in finding suitable phages. The uropathogenic strain E. coli UPEC124, isolated from a patient suffering from neurogenic bladder dysfunction, was found to be resistant to all coliphages in our collections, and initial attempts to isolate new phages failed. Using an improved procedure for phage enrichment, we isolated the N4-related phage Mimir124, belonging to the Gamaleyavirus genus, which was able to lyse this "difficult" E. coli strain. Although Mimir124 is a narrow-spectrum phage, it was effective in the individualized treatment of the patient, leading to pathogen eradication. The primary receptor of Mimir124 was the O antigen of the O101 type; consequently, Mimir124-resistant clones were rough (having lost the O antigen). These clones, however, gained sensitivity to some phages that recognize outer membrane proteins as receptors. Despite the presence of nine potential antiviral systems in the genome of the UPEC124 strain, the difficulty in finding effective phages was largely due to the efficient, non-specific cell surface protection provided by the O antigen. These results highlight the importance of an individualized approach to phage therapy, where narrow host-range phages-typically avoided in pre-fabricated phage cocktails-may be instrumental. Furthermore, this study illustrates how integrating genomic, structural, and functional insights can guide the development of innovative therapeutic strategies, paving the way for broader applications of phage therapy in combating multidrug-resistant bacterial pathogens.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.