biostudies-literatureLi YNIAID NIH HHS8716-21https://www.ebi.ac.uk/biostudies/studies/S-EPMC3365160biostudies-literatureUnknown109(22)Maintenance of membrane function is essential and regulated at the genomic, transcriptional, and translational levels. Bacterial pathogens have a variety of mechanisms to adapt their membrane in response to transmission between environment, vector, and human host. Using a well-characterized model of lipid A diversification (Francisella), we demonstrate temperature-regulated membrane remodeling directed by multiple alleles of the lipid A-modifying N-acyltransferase enzyme, LpxD. Structural analysis of the lipid A at environmental and host temperatures revealed that the LpxD1 enzyme added a 3-OH C18 acyl group at 37 °C (host), whereas the LpxD2 enzyme added a 3-OH C16 acyl group at 18 °C (environment). Mutational analysis of either of the individual Francisella lpxD genes altered outer membrProceedings of the National Academy of Sciences of the United States of AmericaLPS remodeling is an evolved survival strategy for bacteria.PMC3365160T32 AI007540U54 AI057141Pelletier MRGoodlett DRErnst RKLi YRaetz CRRasko DALeszyk JDScott AJMasoudi APowell DAShaffer SAWang XfalseLPS remodeling is an evolved survival strategy for bacteria.Maintenance of membrane function is essential and regulated at the genomic, transcriptional, and translational levels. Bacterial pathogens have a variety of mechanisms to adapt their membrane in response to transmission between environment, vector, and human host. Using a well-characterized model of lipid A diversification (Francisella), we demonstrate temperature-regulated membrane remodeling directed by multiple alleles of the lipid A-modifying N-acyltransferase enzyme, LpxD. Structural analysis of the lipid A at environmental and host temperatures revealed that the LpxD1 enzyme added a 3-OH C18 acyl group at 37 °C (host), whereas the LpxD2 enzyme added a 3-OH C16 acyl group at 18 °C (environment). Mutational analysis of either of the individual Francisella lpxD genes altered outer membr2012-01-01T00:00:00Z2012 May2025-04-04T23:31:07.766Z2019-03-27T00:54:01ZS-EPMC33651602258611910.1073/pnas.1202908109