Coxiella burnetii (Q fever)

Coxiella burnetii is a gram-negative rod that causes a condition called Q fever. This bacterium is highly resistant to environmental stressors including high temperatures and ultraviolet light, and spreads to humans from animals like cows, sheep, and goats, so Q fever is considered a zoonotic infection.

Now, Coxiella burnetii is considered a Gram-negative, obligate intracellular organism. So, it can only replicate inside other cells, like our macrophages. C. burnetii is also non-motile and has a biphasic life cycle that consists of an environmentally stable, non-replicating form called small cell variant, or SCV for short, and a metabolically active, replicating large cell variant, or LCV. When it feels threatened by the environment, like when the temperature becomes too high or too low, in case of extreme dryness, or when there’s harmful radiation around, C. burnetii transforms into the SCV by shrinking and condensing its DNA and periplasmic space. In this form, it is able to resist heat, harsh chemicals, digestive enzymes, and even antibiotics. Remarkably, the SCV can survive for years, waiting for favorable conditions to come, and then convert into the LCV that can then grow and divide inside host cells.

Now, the primary disease that Coxiella burnetii causes is called Q fever. This disease is most commonly acquired by inhalation of aerosolized C. burnetii from an infected animal.

Infection can happen during parturition, when large amounts of bacteria are released in birth fluids, or from dust contaminated by animal excrement, such as when cleaning a barn. It can also be picked up through ingestion of raw milk or other unpasteurized dairy products, or by contact with contaminated animal materials.

So, people at highest risk for infection include those in close contact with farm animals such as farmers and veterinarians, and also slaughterhouse workers.

In terms of pathogenesis, the exact mechanism of disease is poorly understood. What is known is that the small cell variant is highly infectious and once it enters the body, it attaches to receptors on phagocytes, like macrophages in the lung. Now normally, phagocytes destroy invading bacteria via endocytosis, which is when bacteria are engulfed by the phagocyte and wrapped in a vesicle called a phagosome. The phagosome normally merges with an acidic intracellular organelle called a lysosome, forming a phagolysosome. Lysosomes release hydrolytic enzymes inside the phagolysosome, which normally destroy the invading bacteria. But here’s the thing, C. burnetii is unusual because instead of being destroyed, it can modulate the process, allowing it to survive and even replicate in the acidic phagolysosome. The acidic environment triggers transformation of the SCV to the replicating LCV, and within 24-48 hours, the phagolysosome can be filled with replicating LCV forms! How C. burnetii both avoids destruction by the host’s immune system and replicates so efficiently are still not fully understood.

This ability to survive and replicate inside macrophages allows it to travel through the bloodstream to infect multiple organs such as the heart, especially the valves, liver, central nervous system, lymph nodes, and others.