This week, Dr. Daniel Unterweger invites you to temporarily escape the usual world of immunology. Daniel completed his PhD in Bacteriology at the University of Alberta in Edmonton, Canada, and continues his research on microbes as a postdoctoral research fellow at the University of Oxford, UK. Sharing his passion for the microbial world, he sends us a blog post just in time for Carnival.
Carnival is such a great time of the year. Particularly the opportunity to dress up in a different costume every year is fun. Do you already have a costume for tonight? You thought of dressing up as a T-cell? The immunologists’ party will for sure have lots of sensing and signaling. What about doing something different this year and take on a role you normally do not find yourself in? Were you ever wondering about what happens to bacteria and viruses beyond causing an immune response of the human body? Is it only the human immune system bacteria have to worry about? Somebody has even told me about viruses attacking bacteria…. Well, there is only one way for you to find out. Here is a costume for you.
Let’s put on the costume – what am I getting into here? The two layered cell wall makes it pretty clear that I am a Gram-negative bacterium. The costume has the shape of a banana, pretty similar to a curved rod. My flagellum enables me to swim and move around as a single cell when I am not joining others in dense microbial communities. The location of the party I am going to tonight is the marine environment. Okay, I get it! Tonight, I will dress up as a Vibrio cholerae bacterium!
It then happens like it sometimes does at these parties, you suddenly find yourself in places you didn’t originally intend to go to. Although I aim for the aquatic environment in my V. cholerae costume, I am taken up by the human body in contaminated food or water. Once taken up orally, I pass the acid barrier of the stomach and colonize the small intestine without invading host tissue. Recognizing some of the costumes around me from last year’s immunology party makes me realize that V. cholerae is encountering the innate and adaptive response of the immune system. Neutrophils are recruited during the acute phase of infection . Increased levels of cytokines such as TNF-α do not make the human body a comfortable place to stay. The adaptive immune response of mainly B-cells and a few T-cells is initiated to provide some long-term immune protection . However, I do not want the party to be over yet, I can defend myself. My V. cholerae costume is equipped with toxins such as hemolysin or RtxA that form pores or crosslink actin, respectively, and are thus toxic to eukaryotic cells of the host . Cholera toxin is my major virulence factor and acts on intestinal epithelial cells. Its production induces massive water efflux into the intestinal lumen. The resulting diarrhoea is the typical syndrome of cholera patients and flushes the bacteria out of the body again. If left untreated, patients might suffer from severe dehydration and even die.
Having successfully left the human body, I find myself in the marine environment and make my way to the buffet for some food and drinks. I feel comfortable in close proximity to zooplankton such as copepods and other delicious seafood that serve as my carbon source. I look around and see that some bacteriophages joined the party, too. Remembering the work of Kimberley Seed, Andreas Camilli and colleagues, I am glad the phages haven’t spotted me yet. Lytic bacteriophages infect V. cholerae, multiply and destroy the bacterium by releasing nascent virions. This form of phage predation affects V. cholerae populations in the environment  and the human host . V. cholerae harbours a PICI-like element (PLE) that reduces the efficiency by which phages lyse V. cholerae by 100,000-fold . In return, phages contain a CRISPR/Cas system with spacers specific for PLE that counteracts the anti-phage mechanism of the bacterium and renders phage infection successful .
Later that night, it gets a little nasty at the bar. Not immune cells, not viruses but other colleagues with similar prokaryotic costumes also want to get one of the last drinks left. Close proximity to my competitors is a prerequisite to use my type VI secretion system (T6SS) , a contractile puncturing device with which I translocate toxic effector proteins into cells I am in direct contact with. Dana MacIntyre and colleagues demonstrated how powerful this killing mechanism can be. When exposing Escherichia coli bacteria to V. cholerae with a functional T6SS or a dysfunctional T6SS, 100,000 times less surviving E. coli were detected after exposure to V. cholerae with a functional T6SS . Bad news for the person in the E. coli costume on my left, but the V. cholerae bacterium on my right should not feel safe either. V. cholerae even uses the T6SS to fight against other strains of the same species [9, 10]. Finally, I end up with another drink before I have to make use of other toxins against prokaryotic cells that do not require direct contact between cells.
I am back at the bench today. In my agenda for this morning, it says “split cells” and “make buffers”. Nothing I need my brain too intensely for after such a night. I enjoyed learning about the bacterium V. cholerae and getting a glimpse of some of its mechanisms to compete with eukaryotic cells, viruses and other bacteria. Considering the diversity of bacteria and viruses, there is much more to learn from other examples. Let’s see which costume I will pick next year. Looking at myself without a costume, my immune cells still impress me and do a pretty good job, I think. They have to – because bacteria can fight back and are prepared not just for encountering eukaryotes, but also viruses and other prokaryotes.
Acknowledgments: I would like to thank my PhD Supervisor Dr. Stefan Pukatzki, who introduced me to the world of Vibrio cholerae. I also would like to acknowledge Nick Davies and the blog team for their comments on a draft of this blog post.
1 Qadri F1, Bhuiyan TR, Dutta KK, Raqib R, Alam MS, Alam NH, Svennerholm AM, Mathan MM. Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut. Gut. 2004 Jan;53(1):62-9.
2 Harris AM1, Bhuiyan MS, Chowdhury F, Khan AI, Hossain A, Kendall EA, Rahman A, LaRocque RC, Wrammert J, Ryan ET, Qadri F, Calderwood SB, Harris JB. Antigen-specific memory B-cell responses to Vibrio cholerae O1 infection in Bangladesh. Infect Immun. 2009 Sep;77(9):3850-6. doi: 10.1128/IAI.00369-09. Epub 2009 Jun 15.
3 Olivier V1, Haines GK 3rd, Tan Y, Satchell KJ. Hemolysin and the multifunctional autoprocessing RTX toxin are virulence factors during intestinal infection of mice with Vibrio cholerae El Tor O1 strains. Infect Immun. 2007 Oct;75(10):5035-42. Epub 2007 Aug 13.
4 Faruque SM, Naser IB, Islam MJ, Faruque AS, Ghosh AN, Nair GB, Sack DA, Mekalanos JJ. Seasonal epidemics of cholera inversely correlate with the prevalence of environmental cholera phages. Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1702-7. Epub 2005 Jan 14.
5 Seed KD, Yen M, Shapiro BJ, Hilaire IJ, Charles RC, Teng JE, Ivers LC, Boncy J, Harris JB, Camilli A. Evolutionary consequences of intra-patient phage predation on microbial populations. Elife. 2014 Aug 26;3:e03497. doi: 10.7554/eLife.03497.
6 Seed KD, Lazinski DW, Calderwood SB, Camilli A. A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity. Nature. 2013 Feb 28;494(7438):489-91. doi: 10.1038/nature11927.
7 Pukatzki S, Ma AT, Sturtevant D, Krastins B, Sarracino D, Nelson WC, Heidelberg JF, Mekalanos JJ. Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1528-33. Epub 2006 Jan 23.
8 MacIntyre DL, Miyata ST, Kitaoka M, Pukatzki S. The Vibrio cholerae type VI secretion system displays antimicrobial properties. Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19520-4. doi: 10.1073/pnas.1012931107. Epub 2010 Oct 25.
9 Unterweger D, Kitaoka M, Miyata ST, Bachmann V, Brooks TM, Moloney J, Sosa O, Silva D, Duran-Gonzalez J, Provenzano D, Pukatzki S. Constitutive type VI secretion system expression gives Vibrio cholerae intra- and interspecific competitive advantages. PLoS One. 2012;7(10):e48320. doi: 10.1371/journal.pone.0048320. Epub 2012 Oct 26.
10 Unterweger D, Miyata ST, Bachmann V, Brooks TM, Mullins T, Kostiuk B, Provenzano D, Pukatzki S. The Vibrio cholerae type VI secretion system employs diverse effector modules for intraspecific competition. Nat Commun. 2014 Apr 1;5:3549. doi: 10.1038/ncomms4549.
Author: Daniel Unterweger