Acinetobacter baumannii is a well-adapted hospital pathogen and recent data from the National Nosocomial Surveillance System (NNIS) showed a substantial increase in the number of cases of A. baumannii-associated nosocomial (hospital acquired) pneumonia, causing 5 - 10% of intensive care unit (ICU)-acquired pneumonia cases in the United States. Moreover, A. baumannii ranks 10th among the most frequent organisms (1.3%) causing monomicrobial nosocomial bloodstream infections in the US and 2 - 10% of nosocomial infections in intensive care units in European hospitals.
The current knowledge concerning the physiological basis of A. baumannii virulence traits is rather limited. The persistence of A. baumannii is attributed to multiple factors but, unfortunately, knowledge regarding the molecular basis for these traits of A. baumannii, i.e. proteins, enzymes and genes involved as well as their regulation by abiotic and biotic factors is largely unknown. The recent rapid development of analytical and bioinformatic tools, genetic and biochemical technologies, structural analysis, cell culture and animal infection models, all available to our consortium, will allow us to address fundamental questions concerning the adaptation and persistence of the nosocomial pathogen A. baumannii by investigating: (i) the mechanisms of metabolic adaptation (P1, P2), (ii) the role of adhesion, invasion and surface-associated motility during infections (P3), (iii) the molecular mechanisms underlying complement resistance (P4), (iv) the molecular basis and regulation of multidrug resistance (P6, P7) and (v) the evolutionary origin, the distribution, genetic, metabolic and virulence attributes of virulence genes and their contribution to the success of A. baumannii (P8). We anticipate to elucidate the mechanisms of A. baumannii virulence and eukaryotic host cell adaptation from the cellular to the structural level employing advanced analytical tools and a broad spectrum of available molecular biological, biochemical, immunological techniques and bioinformatic tools as well as cutting-edge techniques such as static and dynamic flow infections and various in vitro and in vivo infection models. Our proposed interdisciplinary research team comprises internationally recognized experts from different faculties of the Goethe University in Frankfurt am Main comprising medical and nonmedical microbiologists, biochemists and an applied bioinformaticist, the Max-Planck Institute of Biophysics in Frankfurt, the Robert-Koch Institute in Wernigerode, and the University of Cologne. The collaborative research effort will promote regional and transregional interactions between nonclinical and clinical research groups which is essential to successfully address the multiple factors underlying A. baumannii virulence. This is only possible in an interdisciplinary network of researchers.