GENOMIC APPROACHES TOWARD UNDERSTANDING GRAM-NEGATIVE BACTERIAL OUTER MEMBRANE HOMEOSTASIS

Abstract

The asymmetric outer membrane is an essential feature unique to Gram-negative bacteria that acts as a barrier against many antibiotics. The Tol-Pal protein complex has been suggested to be involved in retrograde phospholipid trafficking and invagination of the outer membrane during cell division, although mechanistic details remain largely elusive. To better understand its function(s), we employed two approaches to investigate genetic interaction(s) with the tol-pal locus. We characterized suppressor mutations that reversed the outer membrane defects in tol-pal mutants and revealed a novel mechanism that affected outer membrane permeability without altering the disrupted lipid composition. We also mapped all genetic interactions with the tol-pal locus and demonstrated that Tol-Pal plays crucial roles in both outer membrane biogenesis and cell wall remodeling. Overall, our results support a model where Tol-Pal plays important and direct roles in both outer membrane lipid homeostasis and septal cell wall remodeling.