Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-13021-8
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Funding
- Swiss National Science Foundation (SNF) Ambizione program [PZ00P3_161492, PZ00P3_161492 185529]
- SNF [31003A_153200, 31003A_175557]
- Novartis Foundation for Medical-Biological Research
- OPO Foundation
- German Research Foundation (DFG) [SPP 1617]
- Swedish Research Council [2014-396]
- Swiss National Science Foundation (SNF) [PZ00P3_161492] Funding Source: Swiss National Science Foundation (SNF)
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The facultative intracellular bacterium Legionella pneumophila replicates in environmental amoebae and in lung macrophages, and causes Legionnaires' disease. Here we show that L. pneumophila reversibly forms replicating and nonreplicating subpopulations of similar size within amoebae. The nonreplicating bacteria are viable and metabolically active, display increased antibiotic tolerance and a distinct proteome, and show high virulence as well as the capacity to form a degradation-resistant compartment. Upon infection of naive or interferon-gamma-activated macrophages, the nonreplicating subpopulation comprises ca. 10% or 50%, respectively, of the total intracellular bacteria; hence, the nonreplicating subpopulation is of similar size in amoebae and activated macrophages. The numbers of nonreplicating bacteria within amoebae are reduced in the absence of the autoinducer synthase LqsA or other components of the Lqs quorum-sensing system. Our results indicate that virulent, antibiotic-tolerant subpopulations of L. pneumophila are formed during infection of evolutionarily distant phagocytes, in a process controlled by the Lqs system.
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