biostudies-literatureUnknownCarr JFIn gram-negative bacteria, the outer membrane (OM) acts in conjunction with the peptidoglycan (PG) cell wall as a barrier against physical, osmotic, and toxic environmental stresses including antibiotics. SanA, an inner membrane protein in <i>Escherichia coli</i> K-12, is required for vancomycin resistance at high temperatures (>42 °C) and we have previously demonstrated that SanA impacts sodium dodecyl sulfate (SDS) resistance during stationary phase reached from carbon limitation. However, its function remains unknown. Here, we show that Δ<i>sanA</i> has a synthetic genetic interaction with Δ<i>wecA</i>, a mutation increasing the availability of the isoprenoid carrier for PG biosynthesis. Specifically, the Δ<i>sanA</i> Δ<i>wecA</i> strain demonstrated heightened SDS EDTA sensitivity, RcsbioRxiv : the preprint server for biology2025.06.10.658892https://www.ebi.ac.uk/biostudies/studies/S-EPMC12259093biostudies-literatureImpaired envelope integrity in the absence of SanA is linked to increased Lipid II availability and an imbalance of FtsI and FtsW activities.PMC12259093De Santiago CBBhut SAMitchell AMHerrera CMNan BRobert WeiCarr JFStephen Trent MWarzecha DJfalseImpaired envelope integrity in the absence of SanA is linked to increased Lipid II availability and an imbalance of FtsI and FtsW activities.In gram-negative bacteria, the outer membrane (OM) acts in conjunction with the peptidoglycan (PG) cell wall as a barrier against physical, osmotic, and toxic environmental stresses including antibiotics. SanA, an inner membrane protein in <i>Escherichia coli</i> K-12, is required for vancomycin resistance at high temperatures (>42 °C) and we have previously demonstrated that SanA impacts sodium dodecyl sulfate (SDS) resistance during stationary phase reached from carbon limitation. However, its function remains unknown. Here, we show that Δ<i>sanA</i> has a synthetic genetic interaction with Δ<i>wecA</i>, a mutation increasing the availability of the isoprenoid carrier for PG biosynthesis. Specifically, the Δ<i>sanA</i> Δ<i>wecA</i> strain demonstrated heightened SDS EDTA sensitivity, Rcs2025-01-01T00:00:00Z2025 Jun2025-08-13T03:04:38.907Z2025-08-13T03:04:38.907ZS-EPMC122590934066149710.1101/2025.06.10.658892