Over the years, microbiologists have discovered several mechanisms by which bacteria release toxins and other products into their environment. Gram positive bacteria like Staph and Strep seem to employ one major secretory apparatus whereas gram negative bacteria appear to have evolved six separate ones. This difference probably stems from the fact that gram negative organisms have a more complicated cell wall structure, consisting of a thin layer of peptidoglycan sandwiched between two lipid bilayers.
These secretory mechanisms generally involve a protein channel extending through one or both of the inner and outer bacterial membranes, acting as a tunnel through which materials can exit the bacterium. At least one of these channels, the Type I Secretory System (T1SS), requires energy in the form of adenosine triphosphate (ATP) in order to function. In contrast, the Type VI Secretory System (T6SS) appears to function with or without ATP present. The T6SS is the most recently characterized secretory channel and appears to be widespread in gram negative bacteria. As will be discussed, microbiologists think the T6SS plays an important role in the bacterial stress response as well as the pathogenicity of certain organisms, especially cholera and pseudomonas.
Gram negative organisms produce two major forms of toxins: endotoxins such as lipopolysaccharide (LPS), which remain attached to their cell walls; and molecules known as exotoxins or virulence factors, which they release directly into a person’s body. In the case of Vibrio cholera, one of its exotoxins irreversibly binds to a signal transduction protein called Gs alpha, leading to the uncontrolled release of potassium and water from the cells lining the intestinal lumen. This fluid loss, in turn, results in a massive and sometimes fatal diarrhea. Another gram negative organism called Pseudomonas aeruginosa releases a toxin that shuts down protein synthesis in eukaryotic cells, ultimately killing them. Unlike cholera, most cases of pseudomonas infection occur as a comorbid illness, for example in patients with cystic fibrosis, or in a hospital setting (nosocomial infection).
T6SS: the mechamism of action
According to recent studies, the T6SS works in a manner similar to bacteriophage viruses. These viruses attach to bacterial cells and inject their DNA into their bacterial host through a structure resembling a hypodermic syringe. Once the viral DNA is inside the bacterium, it tends to incorporate itself into the bacterial genome, ensuring that its DNA will be copied every time the bacterium reproduces. The main difference is that gram negative bacteria do not secrete DNA through the T6SS channel, but instead release exotoxins/virulence factors.
The discovery of T6SS is a relatively recent development in the realm of infectious disease. As such, scientists are still in the process of figuring out the significance of this protein complex in various gram negative organisms. In the case of cholera, the T6SS is thought to secrete a virulence factor encoded by the VgrG gene cluster that crosslinks the cytoskeletal protein actin in human enterocytes, possibly making these cells more susceptible to fluid loss. Virulence factors encoded by another gene cluster called Hcp are also released through the T6SS complex in both cholera and pseudomonas. Developing antibiotics against the T6SS and/or the exotoxins secreted through it has become a hot area of research.
