Modulation of the susceptibility of intestinal bacteria to bacteriophages in response to Ag43 phase variation -- a hypothesis.

Escherichia coli is a Gram-negative bacterium which colonizes the intestinal tract of man and other animals. In addition to being a part of the normal bacterial flora of the human intestine, there are a number of enteropathogenic strains of E. coli which cause infections ranging in consequence from diarrhoea to colitis. Antigen 43 (Ag43) is the major phase-variable protein in the outer membrane of E. coli. One benefit for bacteria resulting from phase variation of surface antigens is usually ascribed to evasion of host defences. However, results of recent studies indicate that infection of E. coli by different bacteriophages is inhibited in the presence of certain bile salts and carbohydrates (components present in the human intestine but absent in standard bacteriological media) when cells are in the 'OFF' state for production of Ag43. The inhibition of bacteriophage development was found to be due to a significant impairment in the process of phage adsorption and evidence was presented for the binding of phage to Ag43. Here we present a hypothesis that in the case of Ag43, phase-variation might benefit the host bacterium by modulating the susceptibility to phage infection in the gut. If this hypothesis is true, it may have important implications not only for basic research but also for development of bacteriophage therapy, a re-discovered method of treatment of patients with infectious diseases.