Virulence factors, Pathogenesis and Clinical manifestations of Legionella pneumophila


Legionella pneumophila is a Gram-negative bacterium that can cause a severe pneumonia in humans called Legionnaires` disease (LD) or a mild flu-like illness called Pontiac fever (PF) . The bacterium is widely distributed in natural and artificial aquatic environments, where it parasitizes free-living amoebae . Human infection occurs by inhalation of contaminated aerosols that reach the alveoli and are phagocytosed by alveolar macrophages . However, instead of being killed by these host cells, L. pneumophila is able to survive and replicate within a specialized membrane-bound compartment called the Legionella-containing vacuole (LCV) . This intracellular lifestyle is essential for the pathogenesis of L. pneumophila and requires the expression of a large arsenal of virulence factors that modulate various host cell processes .

Some of the most important virulence factors of L. pneumophila are:

  • Heat shock protein 60 (Hsp60): a chaperone protein that enhances the invasion and cytokine expression in macrophages .
  • Outer membrane protein (OMP): a porin protein that binds to and delivers packaged materials into the eukaryotic cells and inhibits the fusion of phagosomes with lysosomes .
  • Macrophage infectivity potentiator (Mip) protein: a surface-exposed protein that promotes adherence and phagocytosis of L. pneumophila by macrophages .
  • Type II secretion system (T2SS): a secretion system that translocates various enzymes and toxins into the extracellular milieu or into the LCV lumen, such as phosphatase, lipase, nuclease, metalloprotease and hemolysin . The T2SS is required for intracellular growth, evasion of host defenses and environmental persistence of L. pneumophila .
  • Type IV pili (T4P): hair-like appendages that mediate the entry of L. pneumophila into macrophages and influence the trafficking of the LCV .
  • Flagella: whip-like structures that confer motility to L. pneumophila and are involved in bacterial entry, inhibition of host cell apoptosis and modulation of host immune responses .
  • Dot/Icm type IV secretion system (T4SS): a secretion system that translocates more than 300 effector proteins into the host cell cytosol or membrane, where they manipulate various cellular pathways to establish and maintain the LCV . The Dot/Icm T4SS is the major virulence determinant of L. pneumophila and is essential for intracellular replication, bacterial entry, inhibition of host cell apoptosis and egress of L. pneumophila from host cells .
  • Major outer membrane proteins (MOMPs): surface-exposed proteins that are involved in adherence, intracellular replication, biofilm development and horizontal gene transfer of L. pneumophila .

These virulence factors enable L. pneumophila to exploit its host cells as a niche for replication and dissemination, causing severe lung damage and systemic inflammation in susceptible individuals.