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Did anyone else ever wonder why the Black Death bacteria was so effective? It has cousins that don’t really do anything exciting. Yersinia pestis has 3 key virulence factors.
First appearing roughly 6000 years ago from earlier ancestors, pestis has been found in Iron Age and other historic cultures. Sub strains of pestis have been responsible for the Justinian plague, Black Death in the Middle Ages and more recent outbreaks.
Clinically, it has thermosensitive gene promoters that select different genes depending on whether they are a) 30 degrees skin temp from fleas on skin or b) 37 degree aerosol from lung
Virulence 1: assault. Pathogenic gram negative bacteria (pestis is G neg coccobacillus) have a type 3 secretory complex. You don’t know what that is? I had to look it up. Turns out gram negs like shigella, salmonella, plague literally have needles they stab into eukaryotic cells
And secrete nasty bits into them. (From Wikipedia) 
electron microscopy
electron microscopy
Pestis has one of these and it uses it to be mean.
Virulence factor 2: theft. What differentiates pestis from it’s kinder cousins are transporters and capture mechanisms for iron, zinc and amino acids. No one will be surprised therefore the innate immune response to infection is to drop serum levels of such resources.
In fact very sadly a professor of molecular genetics passed away just before 2010 when he became fatally ill from a deactivated lab strain of pestis that never harmed his colleagues or his healthcare professionals. The reason? He had undiagnosed haemochromatosis.
In fact ferritin (binds heme and takes away) is very protective against yersinia pestis; a rise following vaccination protects against pneumonia plague mere hours later. Antibodies take weeks.
Virulence 3: sneakery. Yersinia is a master of innate immune system evasion. First of all it glycosylates its LPS to hide it. It inhibits the inflammasome inside cells. It inhibits cytokine release. It inhibits neutrophil explosion and NETosis.
It then sits inside macrophages, inhibits the autosome vesicles in which it has been consumed, and surfs it round the lymph duct until it finds a lymph node. There, without being presented at court by an antigen presenting cell
It replicates happily, surrounded by adaptive immune cells, until it bursts forth and causes septic shock. The key to yersinia is it has this weird pre inflammatory phase where one has giant buboes but it hasn’t set up an immune response
Then pew pew it’s out in the bloodstream and it’s too late. Oh yes - of the secretory things it uses it’s needle for, it likes to churn out plasminogen activator, which deactivates clotting. It can therefore run riot and no one can stop it. This is a key feature of lethal
Pneumonic plague.
Other nasty secreted proteins from yersinia generally take out actin (so phagocytes can’t form phagocytic membrane cups), ROS production and kinases. It’s ability to wipe out Rho kinase annoyed the human genome so much
the human immune system now has a whole innate defence pathway dedicated to detecting Rho kinase inhibition, in the form of pyrin domains on the inflammasome. Mutations in that cause familial Mediterranean fever.
There was a Madagascan outbreak of pneumonic plague in 2017. It responds generally well to antibiotics but resistance now occurs. There is a vaccine and it has been used in Russia and Asia. US outbreaks have been from domestic cats.
Interestingly various bacteria know exactly where they are in the body due to various ions nearby. e.g salmonella likes formate in the ileum. Proportionate in the caecum inhibits it. So the ileum is where it gets the needle out!
