{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:28:46Z","timestamp":1791822526985,"version":"4.3.4"},"reference-count":50,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI116059, R01AI095396"],"award-info":[{"award-number":["R01AI116059, R01AI095396"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"crossref","award":["Grand Challenge"],"award-info":[{"award-number":["Grand Challenge"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Salmonella enterica<\/jats:italic>\n            serovar Typhi (\n            <jats:italic>S<\/jats:italic>\n            . Typhi) is a human-restricted pathogen that replicates in macrophages. In this study, we investigated the roles of the\n            <jats:italic>S<\/jats:italic>\n            . Typhi type 3 secretion systems (T3SSs) encoded on\n            <jats:italic>Salmonella<\/jats:italic>\n            pathogenicity islands (SPI)-1 (T3SS-1) and SPI-2 (T3SS-2) during human macrophage infection. We found that mutants of\n            <jats:italic>S<\/jats:italic>\n            . Typhi deficient for both T3SSs were defective for intramacrophage replication as measured by flow cytometry, viable bacterial counts, and live time-lapse microscopy. T3SS-secreted proteins PipB2 and SifA contributed to\n            <jats:italic>S<\/jats:italic>\n            . Typhi replication and were translocated into the cytosol of human macrophages through both T3SS-1 and T3SS-2, demonstrating functional redundancy for these secretion systems. Importantly, an\n            <jats:italic>S<\/jats:italic>\n            . Typhi mutant strain that is deficient for both T3SS-1 and T3SS-2 was severely attenuated in the ability to colonize systemic tissues in a humanized mouse model of typhoid fever. Overall, this study establishes a critical role for\n            <jats:italic>S<\/jats:italic>\n            . Typhi T3SSs during its replication within human macrophages and during systemic infection of humanized mice.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Salmonella enterica<\/jats:italic>\n              serovar Typhi is a human-restricted pathogen that causes typhoid fever. Understanding the key virulence mechanisms that facilitate\n              <jats:italic>S<\/jats:italic>\n              . Typhi replication in human phagocytes will enable rational vaccine and antibiotic development to limit the spread of this pathogen. While\n              <jats:italic>S<\/jats:italic>\n              . Typhimurium replication in murine models has been studied extensively, there is limited information available about\n              <jats:italic>S<\/jats:italic>\n              . Typhi replication in human macrophages, some of which directly conflict with findings from\n              <jats:italic>S<\/jats:italic>\n              . Typhimurium murine models. This study establishes that both of\n              <jats:italic>S<\/jats:italic>\n              . Typhi\u2019s two type 3 secretion systems (T3SS-1 and T3SS-2) contribute to intramacrophage replication and virulence.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01137-23","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T13:01:15Z","timestamp":1687352475000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["<i>Salmonella enterica<\/i>\n            serovar Typhi uses two type 3 secretion systems to replicate in human macrophages and colonize humanized mice"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-9033","authenticated-orcid":true,"given":"Meagan","family":"Hamblin","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine , Stanford, California, 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