ABSTRACT
Klebsiella pneumoniae (KP), with production of abundant capsular polysaccharide (CPS), is capable of causing invasive syndrome. Environmental glucose stimuli may increase CPS biosynthesis. We aimed to investigate the relationship between glycemic control and KP-mediated invasive syndrome in diabetic patients and the effect of glucose on CPS biosynthesis. Diabetic patients with community-acquired KP bacteremia were included to study the risk factors of invasive syndrome. KP-M1, a serotype-K1 KP clinical isolate, was used to examine the CPS biosynthesis and cps gene expression, and the effect of exogenous glucose on bacterial phagocytosis and killing. We found that invasive syndrome was significantly more common in diabetic patients who were infected with strains expressing the K1 serotype (adjusted odds ratio [AOR], 8.32; 95% confidence interval [CI], 1.56−44.24; p=0.01), and had poor glycemic control (HbA1c ≥9%; AOR, 5.66; 95% CI, 2.01−15.92; p<0.01). Pre-incubation of KP-M1 in media containing different gradient glucose concentrations enhanced CPS biosynthesis and cps gene expression in high glucose (0.5%) concentration, which leads to increasing bacterial resistance to phagocytosis and killing. High glucose levels reflected by poor glycemic control may stimulate CPS biosynthesis and cps gene expression of highly virulent KP, which increase resistance to phagocytosis and contribute to development of invasive syndrome.
Acknowledgments
We are grateful to Leung Kei Siu, PhD, National Health Research Institutes, for kindly providing the K. pneumoniae strain DT-X. Dr. Chien-Ching Hung at the Department of Internal Medicine, National Taiwan University Hospital is acknowledged for his critical review of this manuscript.
Funding
This work was funded by grants from the Ministry of Science and Technology of Taiwan (MOST 101-2314-B-182A-061-MY3 and MOST 104-2314-B-182A-051-MY2) and Chang Gung Memorial Hospital, Taiwan (CMRPG8D1211).