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This study describes a novel series of UDP-N-acetylglucosamine acyltransferase (LpxA) inhibitors that was identified through affinity-mediated selection from a DNA-encoded compound library. The original hit was a selective inhibitor of Pseudomonas aeruginosa LpxA with no activity against Escherichia coli LpxA. The biochemical potency of the series was optimized through an X-ray crystallography-supported medicinal chemistry program, resulting in compounds with nanomolar activity against P. aeruginosa LpxA (best half-maximal inhibitory concentration (IC50) <5 nM) and cellular activity against P. aeruginosa (best minimal inhibitory concentration (MIC) of 4 μg/mL). Lack of activity against E. coli was maintained (IC50 > 20 μM and MIC > 128 μg/mL). The mode of action of analogues was confirmed through genetic analyses. As expected, compounds were active against multidrug-resistant isolates. Further optimization of pharmacokinetics is needed before efficacy studies in mouse infection models can be attempted. To our knowledge, this is the first reported LpxA inhibitor series with selective activity against P. aeruginosa.

Feral swine root, or dig, for food and create wallows, thereby destroying sensitive vegetation, displacing native wildlife, and ultimately leading to loss of habitat quality and value. In coastal wetlands, their rooting decreases underground production and expansion of the root zone, exacerbating coastal erosion and land loss (Ashe, 2009). Rooting activities in forested habitats impact forest regeneration and vegetation structure and may lead to increases in invasive plants, including Chinese tallow tree (Triadica sebifera) and cogon grass (Imperata cylindrical). Hurricane protection levees and other water control structures that protect human communities have been severely damaged by rooting. In agricultural lands, feral swine consume crops, damage crop fields, prey on livestock, and create potentially hazardous conditions for the operation of farm equipment (Hamrick and others, 2011). Feral swine compete for food directly with many native animals-such as ducks, deer, squirrels, turkeys, and bears-and destroy habitat

The USGS and the Gulf of Mexico knowledge, and tools required to facilitate management decisions that promote restoration, increase coastal resilience, and mitigate risks associated with both artificial and natural hazards.

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