{"doi":"10.1128/mbio.01137-23","title":"<i>Salmonella enterica</i> serovar Typhi uses two type 3 secretion systems to replicate in human macrophages and colonize humanized mice","abstract":"ABSTRACT Salmonella enterica serovar Typhi ( S . Typhi) is a human-restricted pathogen that replicates in macrophages. In this study, we investigated the roles of the S . Typhi type 3 secretion systems (T3SSs) encoded on Salmonella pathogenicity islands (SPI)-1 (T3SS-1) and SPI-2 (T3SS-2) during human macrophage infection. We found that mutants of S . 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 S . 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 S . 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 S . Typhi T3SSs during its replication within human macrophages and during systemic infection of humanized mice. IMPORTANCE Salmonella enterica serovar Typhi is a human-restricted pathogen that causes typhoid fever. Understanding the key virulence mechanisms that facilitate S . Typhi replication in human phagocytes will enable rational vaccine and antibiotic development to limit the spread of this pathogen. While S . Typhimurium replication in murine models has been studied extensively, there is limited information available about S . Typhi replication in human macrophages, some of which directly conflict with findings from S . Typhimurium murine models. This study establishes that both of S . Typhi’s two type 3 secretion systems (T3SS-1 and T3SS-2) contribute to intramacrophage replication and virulence.","journal":"mBio","year":2023,"id":358553,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1108954,"name":"Ruth Schade","orcid":"0000-0002-5689-4993","position":1,"is_corresponding":false},{"id":1108955,"name":"Ramya Narasimhan","orcid":"0000-0002-2581-2342","position":2,"is_corresponding":false},{"id":350838,"name":"Denise M. Monack","orcid":"0000-0003-3804-2209","position":3,"is_corresponding":false},{"id":1032303,"name":"Meagan Hamblin","orcid":"0000-0001-9989-9033","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:13:48.379546Z","pmid":"37341487","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}