The major causes of atypical bacterial pneumonia are Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. Other common pathogens that may cause similar presentation include viruses (e.g., influenza virus, adenovirus, and hantavirus), other bacteria (such as other Legionella species and other Chlamydophila species), and zoonotic pathogens, such as Coxiella burnetii.[7]

M pneumoniae is a small, free-living bacterium with one of the smallest known genomes. Unlike many other bacteria, it does not have a cell wall. Humans are thought to be the only hosts.[4]C pneumoniae is an obligate intracellular gram-negative bacterium. Humans are thought to be the only host.[8]L pneumophila is a gram-negative bacterium with the ability to live both in extracellular and intracellular environments. In nature it infects amoeba. Humans are accidental hosts through exposure to contaminated water.[24]C burnetii is an obligate intracellular bacteria with gram-negative cell wall. This zoonotic pathogen has a wide range of hosts, which includes arthropods, fish, birds, and mammals. It has a spore-like formation that is resistant to environmental stress and thus promotes its virulence either by inhalation or ingestion.[20]


Transmission of Mycoplasma pneumoniae occurs from human to human. This pathogen has a unique organelle that allows it to attach to respiratory ciliated epithelia. It also exhibits gliding motility on surfaces, which is thought to promote infection.[4] It may produce toxins that cause persistent cough.[25] Another suggested feature is that the immunologic response to this pathogen might promote acute exacerbations of asthma.[26]

Chlamydophila pneumoniae is also transmitted from human to human. Upon infection, its intracellular lifestyle enables it to grow in many cell types, such as macrophages and smooth muscle and endothelial cells. Its ability to inhibit ciliary action is thought to promote persistent cough.[8] As with M pneumoniae, immunologic response to infection may promote acute exacerbations of asthma.[26]

Infection with Legionella pneumophila occurs when humans are exposed to infested water. No human-to-human transmission was thought to occur, but cases suggestive of human transmission were reported in 2016.[27] Within the host, L pneumophila invades phagocytic cells and exploits the host's response to its own benefit, evading degradation and killing.[24][28]

Coxiella burnetii is transmitted either by inhalation, or by ingestion of contaminated animal products. Human-to-human transmission is rare. Although C burnetii causes pneumonia, in many cases it causes acute hepatitis with or without pneumonia or chronic systemic infections.[20]

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