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Brazil consistently ranks among the countries with the highest number of leprosy cases. Data from our group showed that\n                      <jats:italic toggle=\"yes\">M. leprae<\/jats:italic>\n                      upregulates the mevalonate pathway (MP), contributing to the accumulation of cholesterol-ester-enriched lipid droplets in infected macrophages, and that the inhibition of this pathway by statins decreases bacterial intracellular viability. It has already been shown that part of the deleterious effect of statins on\n                      <jats:italic toggle=\"yes\">M. leprae<\/jats:italic>\n                      survival is related to the reduced cholesterol levels, which\n                      <jats:italic toggle=\"yes\">M. leprae<\/jats:italic>\n                      oxidizes to generate reductive power. According to the literature, statins, by inhibiting MP, increase the production of the inflammatory cytokine IL-1\u03b2 through the negative modulation of the biosynthesis of the isoprenoid geranylgeranyl pyrophosphate (GGPP) and farnesyl pyrophosphate (FPP), which are responsible for protein prenylation. In the present study, we tested the hypothesis that part of the effect of statins on the intracellular viability of\n                      <jats:italic toggle=\"yes\">M. leprae<\/jats:italic>\n                      comes from their impact on IL-1\u03b2 production via decreased prenylation. We demonstrate that GGPP is essential in macrophage\n                      <jats:italic toggle=\"yes\">\u2013M. leprae<\/jats:italic>\n                      interaction since the MP inhibitors, pamidronate and GGTI-298, which inhibit the enzymes farnesyl pyrophosphate synthase and geranylgeranyl transferase-1, respectively, decreased the intracellular viability of\n                      <jats:italic toggle=\"yes\">M. leprae<\/jats:italic>\n                      , measured by RT-qPCR. MP inhibitors increased IL-1\u03b2 production by activating the inflammasome, but this effect was reversed with GGPP. IL-1\u03b2 levels were inversely related to bacterial survival. In conclusion, our findings highlight the potential role of protein geranylgeranylation in\n                      <jats:italic toggle=\"yes\">M. leprae<\/jats:italic>\n                      pathogenesis and suggest new therapy options for leprosy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Mycobacterium leprae<\/jats:italic>\n                      , the bacterium that causes leprosy, survives and replicates inside macrophages. Statins, which inhibit the mevalonate pathway, promote bacterial killing in macrophages by affecting cholesterol and isoprenoid production. Cholesterol is crucial for\n                      <jats:italic toggle=\"yes\">M. leprae<\/jats:italic>\n                      survival in macrophages, which explains the microbicidal effect of statins on the bacteria. However, the role of isoprenoid inhibition in statin-induced bacterial killing has not been explored. Isoprenoid groups are added to about 2% of the mammalian proteins, ensuring their proper function. This study focused on geranylgeranyl pyrophosphate (GGPP) and found that inhibiting GGPP formation or protein prenylation in infected macrophages triggered IL-1\u03b2 production, thereby controlling mycobacterial infection. The findings highlight the importance of protein prenylation in\n                      <jats:italic toggle=\"yes\">M. leprae<\/jats:italic>\n                      and suggest new therapeutic strategies for leprosy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00185-25","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T13:00:23Z","timestamp":1756299623000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Impact of protein prenylation inhibition on\n                    <i>Mycobacterium leprae<\/i>\n                    viability and IL-1\u03b2 production in infected macrophages"],"prefix":"10.1128","volume":"207","author":[{"given":"Matheus","family":"da Silva Rocha","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio Marcos","family":"Rodrigues Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pl\u00ednio Marcos","family":"Freire dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Alves Dias","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Pontes Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ)","place":["Rio de Janeiro, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Sammarco Rosa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01dk36s50","id-type":"ROR","asserted-by":"publisher"}],"name":"Divis\u00e3o de Pesquisa e Ensino, Instituto Lauro de Souza Lima","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele F. 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