Identifying Host Human Products Responsible For Natural Transformation of Resistance Traits in Acinetobacter Baumannii

PROJECT SUMMARYIn recent years, a massive increase in the rates of antibiotic resistant bacteria has been observed in clinicalsettings, causing significant concern from both the scientific community and government agencies. Among thepathogens causing these alarming infections is Acinetobacter baumannii, a microorganism that has developedresistance to almost all available antibiotics. Its extreme genome plasticity, largely facilitated by horizontalgenetic transfer (HGT) processes, has contributed to its remarkable antibiotic-resistance phenotype.Transformation seems to be a particularly important HGT mechanism in this bacterium. However, theenvironmental signals triggering competence for natural transformation, the putative effectors involved in thisprocess, and the molecular basis of this phenomenon are still poorly understood. Using the A. baumannii A118clinical isolate as a model, the proposed project will examine the role of human host products as chemicalinducers of DNA uptake. Considering our preliminary data, which show that different albumins cause asignificant increase in the level of transformation frequency, this study will examine the role of Human SerumAlbumin (HSA) and albumin-derived peptides in the development of bacterial competence and the uptake offoreign DNA (Aim 1). Moreover, we will determine the effects of HSA using a whole-genome transcriptionalprofiling approach in A118 (Aim 2). Through this last approach, we expect to identify genes and RNAregulators involved in natural transformation. This knowledge will provide critical insights into the molecular andcellular mechanism this pathogen uses to acquire resistance genes. Future studies can then use these findingsto develop novel approaches to treat severe Acinetobacter human infections, particularly those caused byemerging multidrug-resistant isolates.