Adenylate Cyclase and the Cyclic AMP Receptor Protein Modulate Stress Resistance and Virulence Capacity of Uropathogenic Escherichia coli Grant T. Donovan, J. Paul Norton, Jean M. Bower,* Matthew A. Mulvey INFECTION AND IMMUNITY, 31 Oct. 2012, p. 249–258 Presenter :Yao-Yi Zeng Commentator : Ching-Hao Teng Ph.D Date/Time : 2013/06/13 17:00 -18:00 Location : Room 601,Med College Building Background: To colonize the urinary tract effectively, UPEC employs a variety of virulence factors and stress resistance mechanisms. Uptake limited carbon sources within the urinary tract is also critical to the UPEC. But understanding about the influence of bacterial metabolism pathway in the progress of UPEC infection is still incomplete. In the recent study, QseBC, a two component system, had shown to modulate carbon flux through metabolic pathways and the expression of virulence factors like type 1 pili and flagella. Therefore, it seems that a variety of systems play important roles in the regulation of UPEC virulence and stress resistant mechanism, and make UPEC can sense and respond to the various carbon sources within the host environment. Hypothesis: cAMP-CRP is critical to the ability of UPEC to catabolize amino acids and handle harsh environmental stresses. Results: In the UPEC reference strain UTI89, the deletion of genes encoding CyaA or Crp does not affect the growth in the presence of glucose. But these deletion mutants are unable to utilize amino acids as the sole carbon source. Furthermore, the ability of these mutants to colonize the bladders of mice dependent upon the host innate defenses and significantly attenuated. In in vitro, the cyaA and crp mutants are both sensitive to reactive nitrogen species and superoxide radicals generated by methyl viologen but highly resistant to hydrogen peroxide and acid stress. The resistant to hydrogen peroxide and acid stress is partly attributed by the expression of the alternate sigma factor RpoS and RpoS-regulated gene products include catalases and DNA-binding ferritin-like protein Dps. Conclusion: These data indicate that cAMP-CRP imply to the ability of UPEC to utilize amino acids and appropriately response to environmental stresses include acid stress, which are characteristics related to bacterial fitness and survival within the urinary tract.