Molecular tools for bifidobacteria to study their effects on human health

Bifidobacteria are important group of anaerobic, Gram-positive bacteria of the lower intestinal tract of humans particularly abundant in breast-fed infants. Various health-promoting properties are attributed to the presence of bifidobacteria in the gut. Based on these health-promoting properties, bifidobacteria are widely used as so-called probiotic supplements in pharmaceutical and dairy products. For some strains, anti-inflammatory effects have been reported in vitro and in preclinical studies. Thus, one potential field of application is their use as alternative or supplementary treatment in inflammatory conditions of the gastrointestinal tract.

In previous studies, our group has identified Bifidobacterium spp. strains that show high adhesion to intestinal epithelial cells and display potent anti-inflammatory activity in vitro and in murine models of colitis (Grimm et al., 2015; Philippe et al., 2011; Preising et al., 2010). To unravel the molecular mechanisms of host colonization and anti-inflammatory activity, we sequenced the genomes of several strains of bifidobacteria (Bottacini et al., 2010; Zhurina et al., 2013, 2011) and identified a number of candidate genes potentially involved in these properties (Westermann et al., 2012). Past and current projects aim at investigating the role of these candidates to adhesion, colonization and inhibition of inflammation (Gleinser et al., 2012; Grimm et al., 2015; Wei et al., 2014). A further aspect is the potential use of bifidobacteria as vectors to for delivery of therapeutic genes into solid tumors (Osswald et al., 2015a).

Due to the notorious resistance of bifidobacteria to genetic manipulation, especially the generation of defined mutant strains, we are mainly active in developing new molecular tools for these organisms (Figure 3; Grimm et al., 2014; Osswald et al., 2015b; Sun et al., 2014). Currently we are exploring the possibility for precise genetic engineering of bifidobacteria e.g. using CRISPR/Cas-based molecular tools.


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Figure: Overlay of brightfield and fluorescence microscopy images of primary human macrophages containing different B. bifidum strains labeled by plasmid-based expression of different fluorescent proteins inside. Pictures were acquired on a Zeiss Axio Observer.Z1 microscope with a 63x objective. Image courtesy of V. Grimm (University of Ulm), all rights reserved.