{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T21:07:02Z","timestamp":1767992822500,"version":"3.49.0"},"reference-count":63,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["421867\/2018-3; 303671\/2019-0;314366\/2020-2"],"award-info":[{"award-number":["421867\/2018-3; 303671\/2019-0;314366\/2020-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Mycobacterium bovis is the causative agent of tuberculosis in domestic and wild animal species and sometimes in humans, presenting variable degrees of pathogenicity. It is known that PknG is involved in the first steps of Mycobacterium tuberculosis macrophage infection and immune evasion. We questioned whether M. bovispknG genes were conserved among mycobacteria and if natural genetic modifications would affect its virulence. We discovered a single mutation at a catalytic domain (R242P) of one M. bovis isolate and established the relation between the presence of R242P mutation and enhanced M. bovis virulence. Here, we demonstrated that R242P mutation alters the PknG protein conformation to a more open ATP binding site cleft. It was observed that M. bovis with PknG mutation resulted in increased growth under stress conditions. In addition, infected macrophages by M. bovis (R242P) presented a higher bacterial load compared with M. bovis without the pknG mutation. Furthermore, using the mouse model of infection, animals infected with M. bovis (R242P) had a massive innate immune response migration to the lung that culminated with pneumonia, necrosis, and higher mortality. The PknG protein single point mutation in its catalytic domain did not reduce the bacterial fitness but rather increased its virulence.<\/jats:p>","DOI":"10.3390\/microorganisms10040673","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T23:30:23Z","timestamp":1647991823000},"page":"673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mycobacterium bovis PknG R242P Mutation Results in Structural Changes with Enhanced Virulence in the Mouse Model of Infection"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4470-8444","authenticated-orcid":false,"given":"F\u00e1bio Muniz de","family":"Oliveira","sequence":"first","affiliation":[{"name":"Tropical Pathology and Public Health Institute, Federal University of Goi\u00e1s, Goiania 74605-050, Brazil"},{"name":"Department of Biomedical Sciences, Faculdade Est\u00e1cio de S\u00e1 de Goi\u00e1s\u2014FESGO, Goiania 74063-010, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor Oliveira","family":"Procopio","sequence":"additional","affiliation":[{"name":"Tropical Pathology and Public Health Institute, Federal University of Goi\u00e1s, Goiania 74605-050, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8944-8148","authenticated-orcid":false,"given":"Gabriela","family":"de Lima Menezes","sequence":"additional","affiliation":[{"name":"Biosystem Collaborative Nucleus, Federal University of Jata\u00ed, Jatai 75804-020, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5624-4790","authenticated-orcid":false,"given":"Roosevelt Alves da","family":"Silva","sequence":"additional","affiliation":[{"name":"Biosystem Collaborative Nucleus, Federal University of Jata\u00ed, Jatai 75804-020, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Kipnis","sequence":"additional","affiliation":[{"name":"Tropical Pathology and Public Health Institute, Federal University of Goi\u00e1s, Goiania 74605-050, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-6617","authenticated-orcid":false,"given":"Ana Paula","family":"Junqueira-Kipnis","sequence":"additional","affiliation":[{"name":"Tropical Pathology and Public Health Institute, Federal University of Goi\u00e1s, Goiania 74605-050, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.sbi.2009.10.017","article-title":"Signaling mechanisms of the Mycobacterium tuberculosis receptor Ser\/Thr protein kinases","volume":"19","author":"Alber","year":"2009","journal-title":"Curr. 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