Thursday, October 31, 2013

Bacterial Exocytosis


     It's a month since I posted in this blog. Have been pretty inconsistent I see. Well, after a series (must say a huge series), of posts on viruses especially HIV, today intend to post on some interesting bacteriology. Bacteria's are amazing single cell machines (any cell is for that matter). It is often defined that bacteria's are super competitors for survival. They can help their own kind (Passing on resistance genes is the best example), or attack other bacteria (such as Bacteriocin's) all in the context of survival, in a given niche.

    Communication is an expensive part for the bacteria. Quorum sensing is now a well studied field of Molecular Bacteriology, which decides the aprox count of microbe load and even type of microbe which is followed by decision to multiply, latent or annihilate depending on the situation. Clearly It comes as no surprise when studies find that there are universal and species specific communication molecules which are mis-used or cheated (evolution is marvelous) to gain advantage over the other. Quorum sensing is currently explored as the area of novel bacterial therapeutics.

   The second thing that strikes my thinking when i talk about bacterial communication systems is the Toxin anti-toxin system (TAT; Refer my previous post here). There are many other communication systems which i can think of especially conjugation for gene transfer, and I would argue that, all this are expensive process. Expense here refers to energy. All of these systems requires that molecules to deployed into the external environment, from which an answer mayn't always be available as the environment is a huge system in which molecules can diffuse and drift away leading to waste of energy spent on that molecule. So, as a strategy many microbes have evolved to produce the messengers only when in contact or messaging using a special package system. These are called as outer membrane vesicles (OMVs).

Table 1: Virulence factors and activities associated with native OM vesicles. Source
Fig 2: Formation of OMV
     Membrane vesicles have been explored as a mode of drug delivery or as vector for vaccines. The OMV have been identified as a stress response signal, and a variety of stress have been used to induce OMV production in cell. Form the bacterial perspective, OM vesicles have important functions, with special reference to virulence. Some of the medically important ones are listed in Table 1.

     This field is well investigated, for it signifies some important understanding of molecular delivery system. The current understanding goes something like this. Stress the bacteria and bacteria intends to respond by making molecules which is packed into a vesicles, pinched out of the cell and expressed out as OMV. Apparently the vesicle does the job.

     The intricate details of this machinery has not been worked out (Am sure there are a lot of microbiologists studying this area). The idea that vesicle contains membrane proteins makes it a good candidate for vaccine. Meningococcus doesn't need an introduction. Based on a recent literature search I can quote several journal papers that have used this approach to create vaccines against meningococcus. The basic idea seems to be, to extract the OMV using a stress such as Bile salts (Ex: Deoxycholate) and use it as a vaccine material.

   But what really impressed me is 2 features- First this is an incredibly similar event to exocytosis and so am tempted to coin the term Bacterial Exocytosis (Oops!! That term is my intellectual invention). Second, this seems to me an excellent candidate for toxin delivery by bacteria. The vesicles are bi-layered lipid substances which can be easily taken up (for argument sake say by the host cell). And a little google search tells me that this has been already been demonstrated to be the case, at least in some bacteria (best literature example i could find was on Listeria).

    So here's what makes sense to me. Host can stress the bacteria with a variety of products. Bacteria doesn't wanna waste a lot of molecules all over the environment, so puts in a vesicle and send it out which is easily bumped into a receptor, or directly taken inside the cell delivering the effect right where it is required. It strikes to me immediately that the Table 1 is too short to cite examples as reference possibilities.

   However a question pops. What gene kind of gene system does this relate to? I ask this question since such a tightly regulated system should be managed by a very good feedback bacterial genetic system. It has been shown that all the membrane proteins are not seen in vesicles during vesicle maturation and hence hints to some sort of "membrane editing process" before exocytosis. Whatever is the answer, bacteria have invented exocytosis (At least in a traditional sense) before eukaryotes did.
Ellis TN, & Kuehn MJ (2010). Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiology and molecular biology reviews : MMBR, 74 (1), 81-94 PMID: 20197500

Kulp, Adam. (2010-10-13) Biological Functions and Biogenesis of Secreted Bacterial Outer Membrane Vesicles. , 64(1), 163-184. PMCID:PMC3525469

Berleman, James. (2013-02--1) The role of bacterial outer membrane vesicles for intra- and interspecies delivery. , 15(2), 347-354. DOI:10.1111/1462-2920.12048

Norheim, G. (2012-08--1) An Outer Membrane Vesicle Vaccine for Prevention of Serogroup A and W 135 Meningococcal Disease in the African Meningitis Belt. , 76(2), 99-107. PMID:22537024

Wedege, E. (2013-06--1) Meningococcal Omp85 in Detergent-Extracted Outer Membrane Vesicle Vaccines Induces High Levels of Non-Functional Antibodies in Mice. , 77(6), 452-459. PMID:23521186