Amoeba-resistant species of the genus Legionella or Mycobacterium grow within environmental protozoa in distinct pathogen vacuoles. Upon inhalation, the bacteria replicate within macrophages in the lung and trigger respiratory diseases such as Legionnaires’ pneumonia or tuberculosis. Our research aims at elucidating the specific virulence mechanisms and at identifying novel compounds effective against respiratory pathogens to control their growth in clinical and environmental settings.