Showing posts with label app. Show all posts
Showing posts with label app. Show all posts

Sunday, June 1, 2014

This Month in Blastocystis Research (MAY 2014)

To me, this month was mostly about Blastocystis finding its way to the ASM 2014 general meeting. It was a huge honour for me to be one of the speakers in the Parasitology session 'Passion for Parasites', thanks to an invitation from Dr Lynne Garcia and ASM.

ASM2014 took place in Boston Convention and Exhibition Center.
It's pleasing that the Blastocystis research community is continuously expanding. I currently have contact to several research groups who are venturing into Blastocystis research, including epidemiology, genome sequence analysis, and Blastocystis (and other intestinal microbial eukaryotes (IMEs)) as part of the human intestinal microbiome. At the ICOPA2014 conference in Mexico in August, there will be a full session on Blastocystis from an IBS perspective with talks by Dr Pablo Maravilla, Kenneth Boorom, Dr Pauline D Scanlan and myself. There will also be a pre-congress workshop on molecular parasitology which will include Blastocystis subtyping arranged by Dr Juan David Ramirez Gonzalez and myself.

This month we also launched the website for the 1st International Blastocystis Symposium, which can be accessed at www.blastomeeting.com  - we hope that the meeting will receive great interest and contribute to promoting research on Blastocystis and other IMEs. Please go to the site to sign up for updates.

Moving on to 'paper of the month', I would just briefly highlight a study by Wu, Mirza and Tan, who used Caco-2 human colonic cells and different strains of Blastocystis sp. ST4 and ST7 to compare and demonstrate the strains' relative ability to adhere to enterocytes and to disturb cell barrier function. The paper is very interesting for a variety of reasons. For instance it appears that metronidazole resistance may be linked to a fitness cost as indicated by reduced adhesion ability.

But it would be nice to know how the results reflect the in vivo situation: What actually happens in the colon? It may be so that Blastocystis can adhere to enterocytes and even inflict damage as indicated in the paper, but what if Blastocystis is not able to make it anywhere near the enterocytes?

Now, some parasites are intracellular - e.g. Cryptosporidium and microsporidia -, Giardia has a ventral disc by which it can latch on to the intestinal lining; Entamoebas are motile, etc. Blastocystis is neither intracellular, nor is it motile, but can it attach to enterocytes or is it simply being 'kneeded' and passed along with the remaining luminal content by peristalsis? Or is it lodged in the mucus layer perhaps - trapped by chance, or actively making its way to/through it?

In the colon, two mucus layers exist; an inner layer void of bacteria, and an outer layer that serves as a home for some bacteria but that also prevents these bacteria from reaching the inner layer. Hence, the colon inner mucus layer separates the intestinal lining from the trillions of bacteria inhabiting our large intestine and as such has a tremendously important role in limiting bacterial contact with the epithelium and moving bacteria distally. Mucus is produced by our goblet cells and is made up by mucins, highly glycosylated proteins that we cannot degrade. Moreover, these mucins serve as food for commensal bacteria and are highly resistant to protease activity unless destabilised. The mucus layer traps antimicrobial peptides and other immune effectors and hence creates an effective barrier between the mucosal lining and the microbiota.

Some pathogenic bacteria, and also Giardia for instance, have flagella that allow them to move against the flow caused by secreted mucins, towards the intestinal epithelium, - one way of getting past the iron doors of the mucus layer.

Entamoeba histolytica possesses a lectin-like adhesin that enables it to anchor to the inner mucus layer. After actively destabilising the mucus layer, E. histolytica can disrupt the mucus layer by cysteine protease activity and get into contact with enterocytes. By enzyme activity the parasite can cleave MUC2, the major intestinal mucin, and this may be an initial step in a series of events resulting in invasive disease; however, in many cases enzymatic cleavage of MUC2 may be blocked by glycosylation of the cleavage site; this may be one of the explanations why E. histolytica infection may only sometimes proceed to invasive disease.

Recently, Fayer and colleagues observed that in histology sections Blastocystis was seen to adhere to the intestinal epithelium. However, since about 98% of the mucus is water, the mucus layer may vanish completely during histological procedures with important consequences for the interpretation of observations.

I believe that the use of the mucosal simulator of the human intestinal microbial ecosystem (M-SHIME) would be nearly ideal for studying Blastocystis. M-SHIME is an in vitro dynamic gut model that takes advantage of five double-jacketed vessels, respectively simulating the stomach, small intestine and the three colon regions. The model is supplemented with human gut microbiota and mucin-covered microcosms. My colleagues and I have applied for funding in order to use this model to study Blastocystis ecology, but so far, we have not had any luck with the funding agencies.

Genome and transcriptome studies of Blastocystis should also enable us to identify whether this organism has and expresses proteins that facilitate invasion of the mucus layer and adherence to enterocytes and in which way these potential mechanisms may be influenced.



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Literature: 

Hansson GC (2012). Role of mucus layers in gut infection and inflammation. Current Opinion in Microbiology, 15 (1), 57-62 PMID: 22177113

Fayer R, Elsasser T, Gould R, Solano G, Urban J Jr, & Santin M (2014). Blastocystis tropism in the pig intestine. Parasitology Research, 113 (4), 1465-72 PMID: 24535732 

Johansson ME, Sj√∂vall H, & Hansson GC (2013). The gastrointestinal mucus system in health and disease. Nature Reviews  Gastroenterology & Hepatology, 10 (6), 352-61 PMID: 23478383 

Van den Abbeele, P., Roos, S., Eeckhaut, V., MacKenzie, D., Derde, M., Verstraete, W., Marzorati, M., Possemiers, S., Vanhoecke, B., Van Immerseel, F., & Van de Wiele, T. (2012). Incorporating a mucosal environment in a dynamic gut model results in a more representative colonization by lactobacilli Microbial Biotechnology, 5 (1), 106-115 DOI: 10.1111/j.1751-7915.2011.00308.x

Wu Z, Mirza H, & Tan KS (2014). Intra-subtype variation in enteroadhesion accounts for differences in epithelial barrier disruption and is associated with metronidazole resistance in Blastocystis subtype-7. PLoS Neglected Tropical Diseases, 8 (5) PMID: 24851944