OMPorg aims to discover how bacteria organise proteins embedded in their outer membrane and the consequences of this organisation to the organism. Bacteria are an integral part of our bodily physiology – it is estimated they outnumber our own cells around ten-fold – where they play important roles in, for example, digestion. Bacteria can also be harmful, causing a variety of diseases such as typhoid and cholera, a problem that is greatly exacerbated if the organism is resistant to antibiotics. Bacteria can be broadly classified as Gram-positive or Gram-negative; meaning they either do or do not stain with the classic Gram stain. The absence of staining is the hallmark of Gram-negative bacteria, which harbour a second membrane not found in Gram-positive bacteria. This robust ‘outer membrane’ serves many essential functions in Gram-negative bacteria such as protecting the organism against harsh environments, including our immune system, providing a means of adhering to surfaces where bacteria often accumulate, permitting the diffusion and import of nutrients into the cell and excluding major classes of antibiotics that kill Gram-positive bacteria. Consequently, the outer membrane is a complex and adaptable cellular structure that is important for the viability of the organism in different ecological niches and represents a target for new antibiotics. We know much about the composition of the outer membrane and the many proteins and lipids within it since the membrane was discovered over half a century ago. The dogma up until recently was that these components were randomly mixed in the membrane. In 2015 my laboratory discovered that the proteins in the outer membrane are organised into large supramolecular assemblies we call outer membrane protein (OMP) islands, which can be >0.5 µm in diameter. This discovery immediately answered a major question in outer membrane biology; how are OMPs, which drive most aspects of outer membrane function, changed from one generation to the next? In Escherichia coli - our model organism - the answer is that they are pushed outwards towards the two poles of the cell, somewhat like tectonic plates, during growth and replaced by centrally-located new OMP islands. The resulting binary partitioning results in half of bacterial cells having new OMPs after just two divisions. Organisation of proteins in bacteria is not a new concept but previous examples centred on the cytoplasm and the cytoplasmic (inner) membrane. The discovery of OMP islands as an organising principle in the outer membrane of Gram-negative bacteria raises many new questions about this remarkable cellular structure, questions that lie at the heart of OMPorg.
OMPorg has four major objectives, each subdivided into multiple smaller components. The major objectives are as follows: First, what is the molecular basis of OMP island formation? Second, do OMPs influence the functions of proteins in the inner membrane of Gram-negative bacteria? Third, do repository cells endow bacterial populations with OMP memory? Repository cells are those cells that house the majority of old OMPs following cell division. Fourth, do OMP islands coordinate processes in the outer membrane?
