{"doi":"10.1128/iai.00422-24","title":"The interplay between <i>Acinetobacter baumannii</i> ZigA and SltB promotes zinc homeostasis and cell envelope integrity","abstract":"ABSTRACT Acinetobacter baumannii is an opportunistic human pathogen that acquires nutrient metals from the vertebrate host amid infection. During zinc (Zn) scarcity, A. baumannii upregulates the expression of the predicted Zn metallochaperone, zigA . Loss of zigA compromises fitness during Zn deficiency, highlighting its role in this condition. To assess the contribution of ZigA to Zn-deficient A. baumannii , a multiparallel transposon sequencing and genetic interaction mapping approach was used. Transposon insertions in A1S_3027 , encoding a predicted soluble lytic transglycosylase that tailors the bacterial cell wall, were enriched in the Zn-starved Δ zigA transposon library. Based on previous studies as well as structural and sequence homology, we designated A1S_3027 as s oluble l ytic t ransglycosylase B (SltB). Further analyses revealed that inactivating sltB rescued Δ zigA fitness defects during Zn starvation. An A. baumannii Δ zigA Δ sltB mutant demonstrated altered cell envelope structures and increased cellular permeability, highlighting the roles of ZigA and SltB in maintaining cell envelope integrity. Furthermore, these mutants exhibited heightened resistance to β-lactam antibiotics and other cell wall-targeting agents. Alterations in cell envelope integrity in the Δ zigA Δ sltB mutant improved fitness in a murine pneumonia infection model, emphasizing the contribution of ZigA and SltB to A. baumannii pathogenesis. This study elucidates how functional interactions between ZigA and SltB modulate cell envelope integrity and pathogenesis of A. baumannii during Zn depletion. These findings reveal an interplay between metal homeostasis and cell envelope integrity, offering insights into how A. baumannii ZigA contributes to these critical cellular processes.","journal":"Infection and Immunity","year":2025,"id":540163,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":242378,"name":"Juan P. Barraza","orcid":"0000-0001-7057-2598","position":1,"is_corresponding":false},{"id":847793,"name":"Matthew J. Munneke","orcid":"0009-0007-4797-8697","position":2,"is_corresponding":false},{"id":233811,"name":"Evan Krystofiak","orcid":"0000-0002-0043-6977","position":3,"is_corresponding":false},{"id":861264,"name":"Erin R. Green","orcid":null,"position":4,"is_corresponding":false},{"id":250921,"name":"Eric P. Skaar","orcid":"0000-0001-5094-8105","position":5,"is_corresponding":false},{"id":344075,"name":"Jeanette M. Miller","orcid":"0000-0003-3629-8323","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:52:38.861025Z","pmid":"39846731","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":[]}