Acientobacter baumannii is a gram-negative bacillus, which was initially known for causing health-care associated infections. Most recently the experience in Iraq/Kuwait/Afghanistan has reaffirmed the importance of A. baumannii in causing infections in wounded combatants. Further the prevalence of multi-drug and pan- resistant isolates of A. baumannii is increasing, placing us at risk for entering a post-antibiotic era. As a result, the incidence of Acinetobacter infection in all venues is increasing worldwide. The changing epidemiology and incidence of infections due to Acinetobacter establishes it as a pathogen of increasing medical importance. Needless to say, treatment of infections due to Acinetobacter has become challenging. Improved outcomes will require the development of new preventative and/or therapeutic strategies. Unfortunately, significant knowledge gaps exist that need to be filled to accomplish these goals. Vaccine candidates need to by identified and assessed. Virtually nothing is known about capsular polysaccharides in A. baumannii. Surface polysaccharides such as capsule have formed the basis for several successful vaccines directed against extracellular pathogens such as H. influenzae type b, S. pneumoniae, and certain serotypes of N. meningitidis. This approach may also be practical for Acinetobacter. Therefore, the first goal of this proposal, to determine the number and relative prevalence of A. baumannii capsule serotypes, will be accomplished in aim 1. These data will lay the foundation for immunization and protection studies designed to assess capsule as a vaccine candidate, which will be completed in aim 2. Also in aim 2 studies will be performed to determine the structures of 3-5 of the most prevalent capsular serotypes. This information will be used to optimize the method and design of capsule- protein conjugates as needed to optimize immunogenicity. These data will also be used to predict possible immune reactivity to human epitopes. Lastly, structural data will be an additional means to assess the conservation of capsular epitopes. This proposal will generate new and important data and fill knowledge gaps necessary for the development of new preventive approaches to combat A. baumannii, a pathogen of increasing medical importance in the civilian, veteran, and active military populations.
Acinetobacter baumannii is an increasingly important pathogen in the veteran, military and civilian populations. Antimicrobial resistance to many, and in some cases all, antimicrobial agents has made treatment of A. baumannii infections challenging. Safe reliable agents with predictable activity against A. baumannii are presently non-existent. Development of an efficacious vaccine would assist in solving this evolving clinical problem. Virtually nothing is known about the capsular polysaccharides of A. baumannii and this information may lead to novel preventative or therapeutic approaches. The goal of this proposal is to begin to fill this major knowledge gap, which may have has significant translational implications. Studies will be performed that will determine the potential of capsule as a vaccine antigen. Data generated from this proposal have the potential to form the basis for the logical development of novel preventative or perhaps therapeutic measures to improve outcome in A. baumannii infections.
|Diep, John K; Russo, Thomas A; Rao, Gauri G (2018) Mechanism-Based Disease Progression Model Describing Host-Pathogen Interactions During the Pathogenesis of Acinetobacter baumannii Pneumonia. CPT Pharmacometrics Syst Pharmacol 7:507-516|
|Russo, Thomas A; Manohar, Akshay; Beanan, Janet M et al. (2016) The Response Regulator BfmR Is a Potential Drug Target for Acinetobacter baumannii. mSphere 1:|