A primary function of microbial cell envelopes is to provide a semi-permeable barrier that allows the concentration of important molecules inside the cell and the exclusion of potential toxins. In bacteria, there are two main types of cell envelope, Gram-positive and Gram-negative. Gram-positive cell envelopes are more permeable to a larger range of compounds than Gram-negative cells. This has been linked to the broader spectrum of antibiotics that are active against Gram-positive bacteria and the higher degree of success in identifying new antibiotics to treat infections caused by Gram-positive pathogens compared to Gram-negatives.
The Gram-negative cell envelope is complex and comprised of an inner phospholipid membrane and an outer membrane with an outer-leaflet composed largely of lipid-carbohydrates. The passage of solutes across these membranes is controlled by a network of membrane transport proteins. Our research group is using functional genomics and protein biochemistry to define the key factors within the cell envelope that promote or impede the passage of small molecule antimicrobials into representative Gram-negative bacteria, including Acinetobacter baumannii and Escherichia coli, and the overall importance of the outer membrane to the physiology of these bacteria. In the future, this work could help define the properties of small molecules that can enter Gram-negative bacteria and evade efflux.