The molecular mechanisms of action and its relevance to clinical practice

Fimbriae and flagellae are of significance for the attachment to the mucin layer of the human intestinal mucosa. 12

Studies which were designed to elucidate the mole­cular principles of EcN’s action on the gut mucosa, revealed that EcN is able to induce in the colonocytes the synthesis of the antimicrobial peptide human beta-defensin-2 (HBD-2), and  that the HBD-2-stimulating activity relies on the presence of a structurally bound component of the EcN strain, namely the bacterium's own flagella apparatus. 13 

Experiments with various defect mutants revealed that only EcN bacteria able to synthetize an intact flagellum were capable of stimulating the ­production of HBD-2 in the epithelium cells of the colon.

The structural flagellum protein flagellin, which forms the actual flagellum, i. e. the so-called flagellum filament, was identified to be the effective component. The EcN strain expresses two ­microcins 14 and exerts antagonistic actions against foreign bacteria. 15; 16; 17; 18; 19; 20

Relevance to clinical practice

As a consequence for clinical practice, the induction of the body's own defense agents through the action of E. coli strain Nissle 1917 is equivalent to an increase of the general antimicrobial defense capacity of the intestinal mucosa.

This is of special significance to certain gastrointestinal diseases, such as the chronic inflammatory bowel diseases in which the mucosal synthesis of antimicrobial peptides is affected by disease.

12) Troge A et al. More than a marine propeller – the flagellum of the probiotic Escherichia coli strain Nissle 1917 is the major adhesin mediating binding to human mucus. Int J Med Microbiol 2012; 302: 304–314.

13) Schlee M et al. Induction of human beta-defensin 2 by the probiotic Escherichia coli ­Nissle 1917 is mediated through flagellin.Infect Immun 2007; 75(5): 2399–2407.

14) Patzer S I et al. The colicin G, H and X determinants encode microcins M and H47, which might utilize the catecholate siderophore receptors FepA, Cir, Fiu and IroN. Microbiology 2003; 149: 2557–2570.

15) Oelschlaeger TA et al. Inhibition of Salmonella typhimurium invasion into intestinal cells by the probiotic E. coli strain Nissle 1917. Gastroenterology 2001; 120: A326.

16) Boudeau J et al. Inhibitory effect of probiotic Escherichia coli strain ­Nissle 1917 on adhesion to and invasion of intestinal epithelial cells by adherent-invasive ­E. coli strains isolated from patients with Crohn‘s disease. Aliment Pharmacol Ther 2003; 18: 45–56.

17) Altenhoefer A et al. The probiotic Escherichia coli strain Nissle 1917 interferes with ­invasion of human intestinal epithelial cells by different enteroinvasive ­bacterial pathogens. FEMS ­Immunol Med Microbiol 2004; 40: 223–229.

18) Leatham MP et al. Precolonized human commensal Escherichia coli strains serve as a barrier to E. coli O157:H7 growth in the streptomycin-treated mouse intestine. Infect Immun 2009; 77: 2876–2886.

19) Reissbrodt R et al. Inhibition of growth of Shiga toxin-producing Escherichia coli by non­pathogenic Escherichia coli. FEMS Microbiol Lett 2009; 290: 62–69.

20) Kleta S et al. Role of F1C fimbriae, flagella, and secreted bacterial components in the inhibitory effect of probiotic Escherichia coli Nissle 1917 on atypical enteropathogenic E. coli infection. Infect Immun 2014; 82(5): 1801–1812.

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