{"doi":"10.3389/fcimb.2024.1468866","title":"Salmonella Typhi Haplotype 58 biofilm formation and genetic variation in isolates from typhoid fever patients with gallstones in an endemic setting in Kenya","abstract":"Although typhoid fever has largely been eliminated in high-income countries, it remains a major global public health concern especially among low- and middle-income countries. The causative agent, Salmonella enterica serovar Typhi ( S. Typhi), is a human restricted pathogen with a limited capacity to replicate outside the human host. Human carriers, 90% of whom have gallstones in their gallbladder, continue to shed the pathogen for an ill-defined period of time after treatment. The genetic mechanisms involved in establishing the carrier state are poorly understood, but S . Typhi is thought to undergo specific genetic changes within the gallbladder as an adaptive mechanism. In the current study, we aimed to identify the genetic differences in longitudinal clinical S . Typhi isolates from asymptomatic carriers with gallstones in a typhoid endemic setting in Nairobi, Kenya. Whole-genome sequences were analyzed from 22 S . Typhi isolates, 20 from stool samples, and 2 from blood samples, all genotype 4.3.1 (H58). Out of this, 19 strains were from four patients also diagnosed with gallstones, of whom three had typhoid symptoms and continued to shed S . Typhi after treatment. All isolates had point mutations in the quinolone resistance-determining region (QRDR), and only sub-lineage 4.3.1.2.EA3 encoded multidrug resistance genes. There was no variation in antimicrobial resistance patterns among strains from the same patient/household. Non-multidrug resistant (MDR) isolates formed significantly stronger biofilms in vitro than the MDR isolates, p<0.001. A point mutation within the treB gene ( treB A383T) was observed in strains isolated after clinical resolution from patients living in 75% of the households. For missense mutations in Vi capsular polysaccharide genes, tviE P263S was also observed in 18% of the isolates. This study provides insights into the role of typhoid carriage, biofilm formation, AMR genes, and genetic variations in S. Typhi during asymptomatic carriage.","journal":"Frontiers in Cellular and Infection Microbiology","year":2024,"id":469797,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1276625,"name":"Peter Wachira","orcid":"0000-0002-4537-3981","position":1,"is_corresponding":false},{"id":1276626,"name":"John M. Wagacha","orcid":"0000-0002-1694-0860","position":2,"is_corresponding":false},{"id":345188,"name":"Cecilia Mbae","orcid":"0000-0002-6933-248X","position":3,"is_corresponding":false},{"id":345190,"name":"Susan Kavai","orcid":"0000-0003-4617-9985","position":4,"is_corresponding":false},{"id":873987,"name":"Michael Mugo","orcid":"0000-0003-1448-837X","position":5,"is_corresponding":false},{"id":1303875,"name":"M. Mohamed","orcid":null,"position":6,"is_corresponding":false},{"id":666955,"name":"Juan F. González","orcid":"0000-0002-4568-7200","position":7,"is_corresponding":false},{"id":345187,"name":"Samuel Kariuki","orcid":"0000-0003-3209-9503","position":8,"is_corresponding":false},{"id":593201,"name":"John Gunn","orcid":"0000-0002-3821-4827","position":9,"is_corresponding":false},{"id":1276624,"name":"Peter Muturi","orcid":"0000-0002-7048-1685","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:05:32.241298Z","pmid":"39606745","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":[]}