Abstract
Rapidly growing antibiotic resistance among gastrointestinal pathogens, and the ability of antibiotics to induce the virulence of these pathogens makes it increasingly difficult to rely on antibiotics to treat gastrointestinal infections. The probiotic Escherichia coli strain Nissle 1917 (EcN) is the active component of the pharmaceutical preparation Mutaflor® and has been successfully used in the treatment of gastrointestinal disorders. Gut bacteriophages are dominant players in maintaining the microbial homeostasis in the gut, however, their interaction with incoming probiotic bacteria remains to be at conception. The presence of bacteriophages in the gut makes it inevitable for any probiotic bacteria to be phage resistant, in order to survive and successfully colonize the gut. This study addresses the phage resistance of EcN, specifically against lytic T4 phage infection. From various experiments we could show that (i) EcN is resistant toward T4 phage infection, (ii) EcN’s K5 polysaccharide capsule plays a crucial role in T4 phage resistance and (iii) EcN’s lipopolysaccharide (LPS) inactivates T4 phages and notably, treatment with the antibiotic polymyxin B which neutralizes the LPS destroyed the phage inactivation ability of isolated LPS from EcN. Combination of these identified properties in EcN was not found in other tested commensal E. coli strains. Our results further indicated that N-acetylglucosamine at the distal end of O6 antigen in EcN’s LPS could be the interacting partner with T4 phages. From our findings, we have reported for the first time, the role of EcN’s K5 capsule and LPS in its defense against T4 phages. In addition, by inactivating the T4 phages, EcN also protects E. coli K-12 strains from phage infection in tri-culture experiments. Our research highlights phage resistance as an additional safety feature of EcN, a clinically successful probiotic E. coli strain.
Highlights
The healthy human gut is home to human cells and to a complex microbial community which includes bacteria, archaea, protozoa, fungi, and viruses (Lloyd-Price et al, 2016; Manrique et al, 2017)
Escherichia coli strain Nissle 1917 (EcN) possess several fitness factors such as two anti-bacterial microcins responsible for its antagonistic activity against certain other bacteria (Patzer et al, 2003), seven iron uptake systems assisting in efficient colonization of the gut (Grozdanov et al, 2004; Grosse et al, 2006; Valdebenito et al, 2006; Deriu et al, 2013), three fimbrial determinants aiding in biofilm formation and adhesion to epithelial cells, etc. (Lasaro et al, 2009; Kleta et al, 2014), a H1 type flagella responsible for mucin binding and inducing human beta-defensins (Schlee et al, 2007; Troge et al, 2012),a K5 polysaccharide capsule and a semi-rough lipopolysaccharide (LPS) with a unique O6 antigen involved in immunomodulatory effects (Grozdanov et al, 2002; Hafez et al, 2010; Nzakizwanayo et al, 2015)
In order to get some insight into the mode of T4 phage resistance in EcN, samples of E. coli and T4 phage coincubation cultures were examined by microscopy
Summary
The healthy human gut is home to human cells and to a complex microbial community which includes bacteria, archaea, protozoa, fungi, and viruses (Lloyd-Price et al, 2016; Manrique et al, 2017). (Lasaro et al, 2009; Kleta et al, 2014), a H1 type flagella responsible for mucin binding and inducing human beta-defensins (Schlee et al, 2007; Troge et al, 2012),a K5 polysaccharide capsule and a semi-rough lipopolysaccharide (LPS) with a unique O6 antigen involved in immunomodulatory effects (Grozdanov et al, 2002; Hafez et al, 2010; Nzakizwanayo et al, 2015). These fitness factors are said to collectively contribute to the probiotic nature of EcN
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