T3SS and T4SS

T3SS and T4SS

Even though bacteria far predate human existence, we have co-evolved once humans hit the scene.  It may be hard to believe in terms of cell count but our total number of human cells (10 trillion cells) is exceeded by a logarithm by the number of bacteria in our microbiota (100 trillion cells).  We humans carry roughly 35,000 different species of bacteria on us and in us.  Despite the very large variety of bacteria on planet earth only about 100 species cause human illness.  But, these 100 have endured in large part because of adaptations to evade human defense mechanisms. 

One such system is the “secretion system”.  The two most common of which are: type 3 secretion system (T3SS) and type 4 secretion system (T4SS).   One such system made the news the year one of this newsletters authors was born, 1976.  Legionella has used T4SS for a very long time to avoid destruction by one of its natural predators: amoeba.  At an American Legion meeting in Philadelphia in 1976 amoebas (containing Legionella) contaminating the air conditioning ducts in the hotel were inhaled by conventioneers.  Thirty-four people died from the bacteria leaving its safe haven of the amoeba and entering the lungs of the humans.  Hence, the bacteria using this T4SS survival tactic was christened “Legionella”. 

Enterohemorrhagic E. coli (O157) uses a T3SS protein to cause the severe bloody diarrhea that can occur from ingesting contaminated/undercooked meat.  In this case the E. coli uses the T3SS protein to lock itself to the human intestinal cells so it can’t be displaced, meanwhile releasing a toxin that causes the bloody stools. 

H. pylori (another GI pathogen) uses T3SS to lock itself on to stomach cells.  Once firmly attached it then releases another protein called urease, which neutralizes stomach acid so the acid can’t destroy the bacteria.  H. pylori causes stomach ulcers and if it remains untreated over time can cause stomach cancer.  To date, it’s the only bacteria known to cause cancer.

One final example is Yersinia pestis the bacteria that causes plague.  Once Yersinia enters the human blood stream via a rat bite, it is immediately swallowed by our white blood cells.  But before the white blood cells can destroy the bacteria, the Yersinia releases T3SS which inactivates the immune proteins.  The Yersinia then uses its inactivated white blood cell as a taxi cab to carry it throughout the human body.  Perhaps the early Greeks had already known about Yersinia’s trickery leading to their application of treachery via the Trojan horse. 

As bad as this all sounds, the good news is that humans have evolved a multi-dimensional brain.  This in turn has led to many new strategies to fight the pathogenic bacteria.  Two therapies currently being developed are glycodendrimers and pilicides, both of which inactivate the T3SS/T4SS molecules.  Also, in the works is a genetic vaccine that also inactivates the T3SS/T4SS molecules.  Finally, a chemical called salidylidene acylhydrazide is being researched for its ability to prevent bacteria from secreting the T3SS/T4SS proteins. 


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