Role of the cAMP-Dependent Carbon Catabolite Repression in Capsular Polysaccharide Biosynthesis in Klebsiella pneumoniae

Lin, Ching-Ting; Chen, Yu-Ching; Jinn, Tzyy-Rong; Wu, Chien-Chen; Hong, Yi-Ming; Wu, Wen-Hao
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
K. pneumoniae is the predominant pathogen isolated from liver abscesses of diabetic patients in Asian countries. Although elevated blood glucose levels cause various immune problems, its effects on K. pneumoniae virulence are unknown. This study investigated the regulation of capsular polysaccharide (CPS) biosynthesis, a major determinant for K. pneumoniae virulence, in response to exogenous glucose. We found that K. pneumoniae produce more CPS in glucose-rich medium via reduction in cyclic AMP (cAMP) levels. Individual deletion of cyaA or crp, which respectively encode adenylate cyclase and cAMP receptor protein in K. pneumoniae, markedly increased CPS production, while deletion of cpdA, which encodes cAMP phosphodiesterase, decreased CPS production. These results indicate that K. pneumoniae CPS biosynthesis is controlled by the cAMP-dependent carbon catabolite repression (CCR). To investigate the underlying mechanism, quantitative real-time PCR and promoter-reporter assays were used to verify that the transcription of CPS biosynthesis genes, which are organized into 3 transcription units (orf1-2, orf3-15, and orf16-17), were activated by the deletion of crp. Sequence analysis revealed putative CRP binding sites located on Porf3-15 and Porf16-17, suggesting direct CRP-cAMP regulation on the promoters. These results were then confirmed by electrophoretic mobility shift assay. In addition, we found putative CRP binding sites located in the promoter region of rcsA, which encodes a cps transcriptional activator, demonstrating a direct repression of CRP-cAMP and PrcsA. The deletion of rcsA in mutation of crp partially reduced CPS biosynthesis and the transcription of orf1-2 but not of orf3-15 or orf16-17. These results suggest that RcsA participates in the CRP-cAMP regulation of orf1-2 transcription and influences CPS biosynthesis. Finally, the effect of glucose and CCR proteins on CPS biosynthesis also reflects bacterial resistance to serum killing. We here provide evidence that K. pneumoniae increases CPS biosynthesis for successful infection in response to exogenous glucose via cAMP-dependent CCR.


Related Articles

  • YjcC, a c-di-GMP Phosphodiesterase Protein, Regulates the Oxidative Stress Response and Virulence of Klebsiella pneumoniae CG43. Huang, Ching-Jou; Wang, Zhe-Chong; Huang, Hsi-Yuan; Huang, Hsien-Da; Peng, Hwei-Ling // PLoS ONE;Jul2013, Vol. 8 Issue 7, p1 

    This study shows that the expression of yjcC, an in vivo expression (IVE) gene, and the stress response regulatory genes soxR, soxS, and rpoS are paraquat inducible in Klebsiella pneumoniae CG43. The deletion of rpoS or soxRS decreased yjcC expression, implying an RpoS- or SoxRS-dependent...

  • At-home testing essential for all diabetes patients. Sipkoff, Martin // Drug Topics;Oct2002 Supplement, Vol. 146 Issue 19, p28 

    Reports the importance of home testing for all diabetes patients in the U.S. Number of diabetes patients practicing self monitoring of blood sugar; Recognition of the cost effectiveness of home testing.

  • Do you know your blood-sugar level?  // Consumer Reports on Health;Jul2000, Vol. 12 Issue 7, p1 

    Presents a summary of the American Diabetes Association's guidelines on blood glucose testing and provides medical consultants' recommendations on the diets and treatments one should discuss with a doctor in case one's blood level of glucose is high.

  • Good record keeping in diabetes.  // Patient Care;2/15/1995, Vol. 29 Issue 3, p126 

    Discusses the advantages of good record keeping of blood glucose levels for diabetic patients. Monitoring of trends of blood glucose levels; Understanding the responses of the body to diet, exercise and medication.

  • But how are patients in real world settings faring? Dinsmoor, Robert // Countdown;Summer99, Vol. 20 Issue 3, p26 

    Looks at the practice of tight control or keeping the blood glucose levels as close to normal all the time in diabetics. Evidence of tight control; Extent of tight control; Risks; Possibility for achieving tight control; Cost-effectiveness; Problem with adolescents; Benefits for Type 2 diabetes.

  • WHAT'S TO EAT? Barrett, Janet // Countdown;Spring2002, Vol. 23 Issue 2, p44 

    Discusses the impact of technological advances in blood sugar control on the lifestyles of people with Type I diabetes. Definition of a glycemic index; Tips for flexible eating; Scuba diving protocols developed for people with diabetes by Steve Prosterman, diving and field supervisor at the...

  • Managing diabetes. Wheeler, Mark // Inside Tucson Business;12/01/97 Supplement Executive, Vol. 7 Issue 36, p10 

    Dicusses about diabetes. Figures of diabetes in Southern Arizona; Definition of diabetes; Two major types of diabetes; Diagnosis for each type of diabetes; Management of diabetes; Ideal nutrition and exercise for each type of diabetes; Importance of blood glucose monitoring; Complications of...

  • Adolescent Diabetes Self-Management: How Sweet Is It? H. T. // School Health Alert;Jan2012, Vol. 27 Issue 5, p3 

    The article offers information on a study conducted on the diabetes specific family conflict, glycemic control and adherence to blood glucose monitoring, where higher family conflict scores at baseline predicted less frequent blood glucose monitoring.

  • Home blood glucose monitoring: a sticky artefact. Kinmonth, Ann-Louise // British Medical Journal (Clinical Research Edition);1/24/1981, Vol. 282 Issue 6260, p272 

    Focuses on the risk of home blood glucose monitoring in diabetic patients. Reliability of blood glucose monitoring; Danger in administering glucose; Advice in the application of blood glucose monitoring.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics