AssessmentsEhrlichia and Anaplasma
Ehrlichia and Anaplasma
USMLE® Step 1 style questions USMLE
A 30-year-old woman comes to the office because of fatigue, diffuse muscle pain, and intermittent fever for the past three weeks. She is an avid hiker and spends most weekends outdoors. One month ago, she returned from a vacation in Brazil. Her temperature is 37.5°C (99.5°F), pulse is 90/min, respirations are 18/min, and blood pressure is 120/80 mm Hg. Buffy coat examination shows intracytoplasmic vacuoles. Which of the following microbes is the most likely cause of her condition?
Content Reviewers:Viviana Popa, MD
Contributors:Ursula Florjanczyk, MScBMC, Tanner Marshall, MS, Alex Aranda, Rachel Yancey, Alexandru Duhaniuc, MD
Ehrlichia and Anaplasma are two genera of Gram-negative pleomorphic bacteria, which means they can take different shapes - round like a coccus, or coccobacillary, which means somewhere between a spherical coccus and a rod-like bacillus.
The most common species that cause disease in humans are Ehrlichia chaffeensis, which causes a disease called human monocytic ehrlichiosis, or HME, and Anaplasma phagocytophilum, which causes a disease called human granulocytic anaplasmosis, or HGA.
Now, Ehrlichia and Anaplasma have a thin peptidoglycan layer, so they don’t retain the crystal violet dye during Gram staining.
Instead, like any other Gram-negative bacteria, they stain pink with safranin dye.
Both are non-motile, non-spore forming, and obligate intracellular which means they can survive only inside cells.
Finally, Ehrlichia and Anaplasma don’t grow on routine culture media and they need to be cultivated in vitro in different cell lines.
So, Ehrlichia chaffeensis can be isolated in DH82 canine histiocytic cell line and Anaplasma phagocytophilum can be isolated in promyelocytic leukemia HL-60 cell line.
Now, Ehrlichia and Anaplasma enter circulation following a tick bite and once inside the body, they infect circulating leukocytes.
Ehrlichia primarily targets monocytes and macrophages, and it infects them using tandem repeat proteins, or TRP.
These bacterial proteins bind to proteins found on the surface of the cell, and they induce phagocytosis - so basically, they make the cell gobble up the bacteria.
Anaplasma, on the other hand, primarily targets neutrophils, and infects them with the help of a P-selectin glycoprotein which binds on the P-selectin glycoprotein ligand-1, or PSGL-1 found on the surface of neutrophils.
This activates an intracellular pathway that leads to reorganization of cellular actin which leads to phagocytosis, allowing Anaplasma to enter the cell.
Once inside the cell, both Ehrlichia and Anaplasma live in an early endosome, which normally merge with lysosomes to kill invading bacteria.
But, in order to merge with lysosomes, this early endosome needs to become a late endosome.
So, the early endosome contains a protein called rab5A, which is involved in the recruitment of rab7A and the maturation of these compartments into late endosomes.
However, Ehrlichia and Anaplasma don’t let that happen, so it stops the production of rab5A.
How they do that is still unknown, but the end result is that the early endosome can’t become a late endosome, so it doesn’t merge with the lysosome.
Thus, bacteria avoid intracellular killing by lysosomal enzymes.
Additionally, Anaplasma can avoid intracellular killing by inhibiting the production of reactive oxygen species produced by neutrophils to destroy invading bacteria.
Also, it has the ability to destroy XIAP, a protein which normally inhibits neutrophil apoptosis, or programmed cell death.
So, by destroying XIAP, it stimulates neutrophil death.
Now, when they are safe from intracellular killing, Ehrlichia and Anaplasma replicate inside early endosomes by binary fission.
This means the bacteria split in two identical copies - and if it sounds similar to mitosis...well, it is!
But the term binary fission is used to describe division of prokaryotic cells, which don’t have a nucleus, and therefore some steps in replication are different from mitosis.