Molecular interplay between peptidoglycan integrity and outer membrane asymmetry in maintaining cell envelope homeostasis

Loss of LdtJ in Acinetobacter baumannii disrupts cell morphology, downregulates peptidoglycan precursor genes (e.g., dadA, alr), and activates the stringent response, including elevated ppGpp levels and dksA upregulation. These defects are fully suppressed in a ?ldtJ ?mla double mutant, implicating the outer membrane lipid transport Mla pathway in compensatory regulation. RNA sequencing revealed that transcriptional changes in the ?ldtJ mutant are reversed in the double mutant, highlighting a functional interplay between peptidoglycan remodeling and outer membrane lipid asymmetry. Overall design: Differential gene expression in A. baumannii strain ATCC 17978 wild type, ?ldtJ, and ?ldtJ ?mla strains