Studies in a cell model have shown great potential for phage therapy in the treatment of meningitis caused by pathogenic Escherichia coli with the K1 capsular antigen.

Bacterial meningitis is an inflammation of the meninges caused by invasion by meningococci, pneumococci, group B streptococci, pathogenic Escherichia coli , and other microorganisms. It is a serious illness that requires prompt diagnosis and antibacterial and anti-inflammatory therapy. Bacterial meningitis is especially common in newborns (most often premature babies) and young children, as their immune systems are still very immature. The mortality rate for neonatal meningitis is 5-20%, and 25-50% of survivors experience lifelong neurological disorders, including cognitive impairment, deafness, blindness, and seizures.

One of the common pathogens that causes bacterial neonatal meningitis is E. coli , primarily strains that carry the so-called K1 capsular antigen (a polymer of sialic acid that coats the surface of the bacterium and conceals many of its antigens). This capsule is believed to help E. coli evade destruction by the human immune system and penetrate the blood-brain barrier into the brain.

One of the key challenges in treating neonatal meningitis is overcoming antibiotic resistance in E. coli and other pathogens. To this end, scientists from the University of Warwick (UK) investigated the effects of bacteriophages in this condition. They created a model for studying neonatal meningitis using human cerebral microvascular endothelial cells (hCMECs), the E. coli strain EV36, and the K1F bacteriophage, which is specific to this E. coli strain.

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The authors discovered that bacteriophages are capable of infecting E. coli within hCMEC cells. The bacteriophages themselves do not induce either an immune or inflammatory response. However, the bacteriophages temporarily increase the permeability of hCMEC endothelial cells, which in vivo may facilitate the penetration of immune cells through the walls of blood vessels into the brain.

The study, according to the authors, demonstrates the great potential of phage therapy in neonatal meningitis and, overall, is an important step in the development of treatments for antibiotic-resistant bacterial infections.

* Møller-Olsen C, Ross T, Leppard KN et al. Bacteriophage K1F targets Escherichia coli K1 in cerebral endothelial cells and influences the barrier function. Scientific Reports, 2020, 10: 8903. https://doi.org/10.1038/s41598-020-65867-4