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Abstract
The Gram-negative cell envelope provides protection to the cell from the environment. This function is critical for the integrity of the cell, as it prevents passive entry of hydrophilic molecules and precludes access to hydrophobic compounds. In doing so, the Gram-negative cell envelope prohibits the entry of a large swath of currently available antibiotics and presents a massive hurdle for new antibiotic discovery. As such, understanding the mechanisms behind Gram-negative cell envelope biogenesis is important from both a basic and applied perspective. This dissertation explores these processes in the Gram-negative pathogen Acinetobacter baumannii. The outer membrane of A. baumannii, like all other Gram-negatives, is asymmetric in nature, with lipooligosaccharide (LOS) exclusively present in the outer leaflet. However, A. baumannii is relatively unique in that it can survive in the absence of LOS, which normally is essential for survival. This trait makes A. baumannii a powerful tool for studying cell envelope biology in the presence or absence of LOS. Here, we mechanistically explore the biological basis behind how A. baumannii is able to survive in the absence of LOS, the increasingly important role of the Mla pathway in cell envelope homeostasis, and potential links of outer membrane homeostasis to global cellular physiology.