a systems biology approach to drug targets in pseudomonas aeruginosa biofilm系统生物学方法在铜绿假单胞菌生物膜的药物靶点.pdfVIP

A Systems Biology Approach to Drug Targets in Pseudomonas aeruginosa Biofilm 1 1 1 1,2 Gunnar Sigurdsson , Ronan M.T. Fleming , Almut Heinken , Ines Thiele * ´ 1 Center for Systems Biology, University of Iceland, Reykajavık, Iceland, 2 Faculty of Industrial Engineering, Mechanical Engineering and Computer Science, University of ´ Iceland, Reykajavık, Iceland Abstract Antibiotic resistance is an increasing problem in the health care system and we are in a constant race with evolving bacteria. Biofilm-associated growth is thought to play a key role in bacterial adaptability and antibiotic resistance. We employed a systems biology approach to identify candidate drug targets for biofilm-associated bacteria by imitating specific microenvironments found in microbial communities associated with biofilm formation. A previously reconstructed metabolic model of Pseudomonas aeruginosa (PA) was used to study the effect of gene deletion on bacterial growth in planktonic and biofilm-like environmental conditions. A set of 26 genes essential in both conditions was identified. Moreover, these genes have no homology with any human gene. While none of these genes were essential in only one of the conditions, we found condition-dependent genes, which could be used to slow growth specifically in biofilm-associated PA. Furthermore, we performed a double gene deletion study and obtained 17 combinations consisting of 21 different genes, which were conditionally essential. While most of the difference in double essential gen