{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:12:21Z","timestamp":1792735941491,"version":"4.5.0"},"reference-count":410,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Legionella pneumophila<\/jats:italic>\n                    is an environmental bacterium that emerged from a prolonged co-evolution and adaptation to free-living amoebae as the natural hosts. Within these protozoan hosts,\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    evolved to evade amoebae predation and remodel their vacuoles into endoplasmic reticulum (ER)-derived vacuoles that evade phagosomal-lysosomal fusion. The\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    -amoebae co-evolution fortuitously has facilitated infection of human alveolar macrophages, resulting in pneumonia known as Legionnaires\u2019 Disease. Intracellular replication and host manipulation are orchestrated by the Dot\/Icm Type IV Secretion System (T4SS), which translocate more than 350 effectors that remodel host membrane trafficking, metabolism, and immune signaling, and by the Type II Secretion System, which releases \u2248120 hydrolytic enzymes that promote nutrient acquisition and environmental persistence. The extraordinary diversity and redundancy of these effectors reflect evolutionary pressures within diverse protozoan reservoirs that have sculpted an arsenal capable of subverting numerous eukaryotic processes in diverse environmental hosts and is obvious from genomic plasticity. Adaptation of\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    to the intracellular life within unicellular phagocytic amoebae has played a major role in host expansion to human macrophages that share numerous conserved processes with amoebae, which are thought to be their ancestors. However, since\n                    <jats:italic>Legionella<\/jats:italic>\n                    modulate various mammalian-specific processes not present in unicellular amoebae, it is also likely that\n                    <jats:italic>Legionella<\/jats:italic>\n                    has also evolved through interaction with multi-cellular eukaryotic environmental hosts prior the infection of humans. It is also possible that many of the mammalian-specific processes modulated by effectors of\n                    <jats:italic>Legionella<\/jats:italic>\n                    can be an accidental host response to amoebae-adapted effectors rather than specific adaptation. This is a comprehensive review that synthesizes advances in our knowledge of ecology, epidemiology, metabolism, secretion systems, and host-pathogen interactions of\n                    <jats:italic>L. pneumophila<\/jats:italic>\n                    , highlighting how environmental selection and co-evolution with protozoan hosts drive genomic evolution and expansion of the host range from unicellular eukaryotic amoebae to humans.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1787137","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:42:40Z","timestamp":1771483360000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Molecular evolution and adaptations of Legionella pneumophila from amoebae hosts to macrophages"],"prefix":"10.3389","volume":"16","author":[{"given":"Cheon Jee","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville","place":["Louisville, KY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Abu Kwaik","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Center for Predictive Medicine, University of Louisville","place":["Louisville, KY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.chom.2015.07.016","article-title":"Canonical inflammasomes drive IFN-gamma to prime caspase-11 in defense against a cytosol-invasive bacterium","volume":"18","author":"Aachoui","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B2","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1126\/science.1230751","article-title":"Caspase-11 protects against bacteria that escape the vacuole","volume":"339","author":"Aachoui","year":"2013","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1046\/j.1365-2958.1997.3661739.x","article-title":"Transcriptional regulation of the macrophage-induced gene (gspA) of Legionella pneumophila and phenotypic characterization of a null mutant","volume":"24","author":"Abu Kwaik","year":"1997","journal-title":"Mol.Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.1128\/AEM.64.9.3127-3133.1998","article-title":"Invasion of protozoa by Legionella pneumophila and its role in bacterial ecology and pathogenesis","volume":"64","author":"Abu Kwaik","year":"1998","journal-title":"Appl.Environ.Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1128\/IAI.74.5.3021-3026.2006","article-title":"Role for RpoS but not RelA of Legionella pneumophila in modulation of phagosome biogenesis and adaptation to the phagosomal microenvironment","volume":"74","author":"Abu-Zant","year":"2006","journal-title":"Infect. 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