Peptidyl-Prolyl-/-Isomerases Mip and PpiB of Contribute to Surface Translocation, Growth at Suboptimal Temperature, and Infection.

The gammaproteobacterium is the causative agent of Legionnaires' disease, an atypical pneumonia that manifests itself with severe lung damage. , a common inhabitant of freshwater environments, replicates in free-living amoebae and persists in biofilms in natural and man-made water systems. Its environmental versatility is reflected in its ability to survive and grow within a broad temperature range as well as its capability to colonize and infect a wide range of hosts, including protozoa and humans. Peptidyl-prolyl--isomerases (PPIases) are multifunctional proteins that are mainly involved in protein folding and secretion in bacteria. In the surface-associated PPIase Mip was shown to facilitate the establishment of the intracellular infection cycle in its early stages. The cytoplasmic PpiB was shown to promote cold tolerance. Here, we set out to analyze the interrelationship of these two relevant PPIases in the context of environmental fitness and infection. We demonstrate that the PPIases Mip and PpiB are important for surfactant-dependent sliding motility and adaptation to suboptimal temperatures, features that contribute to the environmental fitness of Furthermore, they contribute to infection of the natural host as well as human macrophages and human explanted lung tissue. These effects were additive in the case of sliding motility or synergistic in the case of temperature tolerance and infection, as assessed by the behavior of the double mutant. Accordingly, we propose that Mip and PpiB are virulence modulators of with compensatory action and pleiotropic effects.