PROJECT SUMMARY The prevalence of asthma in the United States is approximately 8% (>25 million people). In African Americans, the prevalence is >11%. A majority of asthma sufferers are sensitized to allergens, including those shed in the feces, saliva, and exuviae of cockroaches. Thus, exposure to cockroach infestation is recognized as both a significant risk factor for the development of allergic asthma and a potent trigger of asthma attacks. The asthma risk from cockroach exposure is particularly high in inner-city residences where elevated levels of cockroach allergens are common. For example, some studies have shown that cockroach allergens are found at high concentrations associated with asthma in >45% of high-rise apartments in the U.S., and >60% of asthmatic children in U.S. inner cities are sensitized to cockroach allergens. Treating active cockroach infestations can significantly reduce allergen levels within structures and is one strategy to improve asthma symptoms that is recommended by the National Asthma Education and Prevention Board. The German cockroach, Blatella germanica, is the most widespread and problematic cockroach pest in urban environments. The use of insecticidal baits has traditionally been the most effective method for control of this species. However, the spread of insecticide resistance across populations of B. germanica can reduce the efficacy of insecticidal interventions, creating a need for improved tools. Our research team recently reported that the gut microbiota contributes to insecticide resistance in B. germanica. We also found that disrupting the gut microbiota decreases reproductive fitness. Accordingly, we predict that targeting the microbiota of German cockroaches by incorporating antibacterial metal oxide nanoparticles into insecticidal bait formulations could be an effective strategy to improve control of insecticide-resistant infestations in the field. We propose three specific aims to test the viability of this approach against cockroaches resistant to diverse insecticides using two types of metal oxide nanoparticles with known antibacterial properties (ZnO and CuO). In aim 1, we will determine if antibacterial nanoparticles can increase the efficacy of several commonly used bait insecticides against resistant cockroach strains. In aim 2, we will determine if antibacterial nanoparticles in bait can adversely affect cockroach life history. In aim 3, we will determine if nanoparticle-insecticide combination baits can eliminate resistant cockroach populations under semi-field conditions. It is expected that the results of our work will inform the development of novel insecticidal bait formulations to mitigate insecticide resistance and improve cockroach control, which has been demonstrated to reduce asthma morbidity and improve outcomes in human populations.