{"doi":"10.1016/j.celrep.2022.110758","title":"PITing it forward: A new link in the journey of uropathogenic E. coli in the urothelium","abstract":"Urinary tract infections (UTIs) are a cause for alarm given the high rates of treatment failure. In a recent issue of Cell Reports, Pang et al. uncovered dueling molecular machinery at the host-pathogen interface in response to phosphate that points to new anti-infective strategies against UTIs. Urinary tract infections (UTIs) are a cause for alarm given the high rates of treatment failure. In a recent issue of Cell Reports, Pang et al. uncovered dueling molecular machinery at the host-pathogen interface in response to phosphate that points to new anti-infective strategies against UTIs. Urinary tract infections (UTIs) are common and frequently recurrent. The majority of UTIs are caused by uropathogenic Escherichia coli (UPEC). Detailed molecular events that underlie UPEC colonization and persistence in the bladder have been characterized in several elegant studies over the past 20 years in mouse models, human cell lines, and organoids. UPEC binding to urothelial cells is followed by a Toll-like receptor 4 (TLR4) signaling pathway that initiates a cascade of signaling events leading to bacterial internalization (Klein and Hultgren, 2020Klein R.D. Hultgren S.J. Urinary tract infections: microbial pathogenesis, host-pathogen interactions and new treatment strategies.Nat. Rev. Microbiol. 2020; 18: 211-226https://doi.org/10.1038/s41579-020-0324-0Crossref PubMed Scopus (129) Google Scholar) through packaging into fusiform vesicles (FVs) of the GTPase RAB27B. From this point, the course of infection can follow several pathways (Figure 1A) wherein UPEC can (1) be expelled into the urinary lumen via the FVs; (2) escape the FV into the cytosol and establish intracellular bacterial communities (IBCs) within the superficial cell, eventually fluxing out of the cell to re-initiate the infection cycle in adjacent cells (Klein and Hultgren, 2020Klein R.D. Hultgren S.J. Urinary tract infections: microbial pathogenesis, host-pathogen interactions and new treatment strategies.Nat. Rev. Microbiol. 2020; 18: 211-226https://doi.org/10.1038/s41579-020-0324-0Crossref PubMed Scopus (129) Google Scholar); (3) be directed to the lysosome for degradation yet still escape by neutralizing lysosomal pH resulting in bacterial expulsion (Miao et al., 2015Miao Y. Li G. Zhang X. Xu H. Abraham S. A TRP channel Senses lysosome Neutralization by pathogens to trigger their expulsion.Cell. 2015; 161: 1306-1319https://doi.org/10.1016/j.cell.2015.05.009Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar); or (4) be recognized by autophagy pathway proteins via intracellular NOD-like receptors and enter autophagosomes where they form quiescent intracellular reservoirs (QIRs), which can persist long-term and re-emerge to cause recurrent UTIs (Mysorekar and Hultgren, 2006Mysorekar I.U. Hultgren S.J. Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract.Proc. Natl. Acad. Sci. U S A. 2006; 103: 14170-14175https://doi.org/10.1073/pnas.0602136103Crossref PubMed Scopus (358) Google Scholar). Molecular details of how UPEC escapes from FVs into the cytosol have remained enigmatic until now, when in a recent issue of Cell Reports Pang et al. uncovered the first steps taken by UPEC to utilize the host response to its advantage, enabling escape from vesicles to establish IBCs (Pang, 2022Pang Y. Bladder Epithelial Cell Phosphate Transporter Inhibition Protects Mice against Uropathogenic Escherichia coli Infection.Cell Rep. 2022; Abstract Full Text Full Text PDF Scopus (3) Google Scholar). This new work also puts a spotlight on the ability of fluctuating phosphate concentrations to trigger high-stakes molecular crosstalk at the host-pathogen interface. Phosphate is essential for the synthesis of ATP, RNA, DNA, and cellular membranes and is carefully controlled. The bladder expresses two type-III phosphate transporters: PIT1 and PIT2 (SLC20A1 and A2) belonging to the solute carrier superfamily of transporters implicated in intr","journal":"Cell Reports","year":2022,"id":290967,"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":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":474611,"name":"Lynette Cegelski","orcid":"0000-0002-0978-1814","position":1,"is_corresponding":false},{"id":314987,"name":"Indira U. Mysorekar","orcid":"0000-0003-3917-8677","position":2,"is_corresponding":false},{"id":646321,"name":"Chetanchandra S. Joshi","orcid":"0000-0002-3637-8414","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-19T00:30:34.502076Z","pmid":"35476986","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":[]}