The recently discovered Akkermansia muciniphila is a strictly anaerobic, mucin-degrading human intestinal bacterium (Derrien et al., 2004). It colonizes a considerable part of the human population and is abundantly present along the gut.
The host phylogeny of A. muciniphila spans the complete mammalian tree and it is also present in some reptiles. The numbers of A. muciniphila have been shown to be lower in intestinal disorders, such as Crohn’s disease and ulcerative colitis (Png et al., 2010), and it therefore has potential to be developed as a biomarker for a healthy intestine.
The entire gastrointestinal (GI) tract of humans is covered by a mucus layer consisting of large glycoproteins (mucins). Mucin degradation is a normal process of mucus turn over in the GI-tract. Many bacteria are able to degrade mucin partially but the complete degradation of mucin requires the action of several bacteria. Since A. muciniphila can use mucin efficiently, it is a good target for studying the mucin-degradation properties of bacteria in the gut. In order to gain better understanding of the interactions between the bacteria and the mucus, the genome was sequenced and the proteome annotated (van Passel et al., 2011). Out of the proteins predicted to be secreted, 61 proteins (11%) were annotated as enzymes involved in the degradation of mucin. Also other host-microbe interactions, including inflammatory responses, can be studied due to the close proximity of the epithelial cells to A. muciniphila.
The aim of this project is to understand the proteome functionality of A. muciniphila under different conditions. Special interest is in proteins that could be related to mucin degradation, adherence to the mucus layer and communication with the host immune system.
State of the art proteomics techniques will be utilized to explore the role of mucin degradation of A. muciniphila in health and disease. Cell fractionation will be carried out by various isolation methods based on the specific properties of proteins from different compartments in order to analyse and characterize bacterial cell components. Analysis of in vivo material, such as faecal samples, with proteomics methods is used to study the proteome expressed under different conditions, for example in relevant disease states. The physiological properties will be studied with fermentation studies using different growth media and substrates. Reporter cell lines and other immune assays will be used to study the immune regulation of A. muciniphila.
- Derrien M, Vaughan EE, Plugge CM, de Vos WM (2004) Akkermansia muciniphila gen. nov.,
sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol 54 (Pt 5):1469-1476.
- Png CW, Lindén SK, Gilshenan KS, Zoetendal EG, McSweeney CS, Sly LI, McGuckin MA, Florin TH. (2010) Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol Nov;105(11):2420-8.
- van Passel MW, Kant R, Zoetendal EG, Plugge CM, Derrien M, Malfatti SA, Chain PS, Woyke T, Palva A, de Vos WM, Smidt H (2011). The Genome of Akkermansia muciniphila, a Dedicated Intestinal Mucin Degrader, and Its Use in Exploring Intestinal Metagenomes. PLoS One Mar 3;6(3):e16876.