title: Impact of glycemic control on capsular polysaccharide biosynthesis and opsonophagocytosis of Klebsiella pneumoniae: Implications for invasive syndrome in patients with diabetes mellitus.
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.
authors.affiliation: a Division of Infectious Diseases, Kaohsiung Chang Gung Memorial Hospital , Kaohsiung , Taiwan.|b Chang Gung University College of Medicine , Kaohsiung , Taiwan.
authors.forename: Chen-Hsiang
authors.initials: CH
authors.lastname: Lee
authors.affiliation: c Department of Pharmacology , Kaohsiung Chang Gung Memorial Hospital , Kaohsiung , Taiwan.
authors.forename: I-Ling
authors.initials: IL
authors.lastname: Chen
authors.affiliation: b Chang Gung University College of Medicine , Kaohsiung , Taiwan.|d Division of Gastroenterology, Kaohsiung Chang Gung Memorial Hospital , Kaohsiung , Taiwan.
authors.forename: Seng-Kee
authors.initials: SK
authors.lastname: Chuah
authors.affiliation: b Chang Gung University College of Medicine , Kaohsiung , Taiwan.|d Division of Gastroenterology, Kaohsiung Chang Gung Memorial Hospital , Kaohsiung , Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Tai
authors.affiliation: a Division of Infectious Diseases, Kaohsiung Chang Gung Memorial Hospital , Kaohsiung , Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Chang
authors.affiliation: a Division of Infectious Diseases, Kaohsiung Chang Gung Memorial Hospital , Kaohsiung , Taiwan.
authors.forename: Fang-Ju
authors.initials: FJ
authors.lastname: Chen
authors.affiliation: b Chang Gung University College of Medicine , Kaohsiung , Taiwan.|e Division of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital , Kaohsiung , Taiwan.
authors.forename: Jung-Fu
authors.initials: JF
authors.lastname: Chen
mesh_terms: D000368:Aged; D016470:Bacteremia / Q000382:microbiology / Q000503:physiopathology; D016667:Bacterial Capsules / Q000187:drug effects / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D048909:Diabetes Complications / Q000382:microbiology*; D003920:Diabetes Mellitus / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007710:Klebsiella Infections / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D007711:Klebsiella pneumoniae / Q000737:chemistry / Q000187:drug effects / Q000472:pathogenicity*; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis; D011446:Prospective Studies; D065288:Serogroup
chemical_list: D001786:Blood Glucose; D005947:Glucose; D006442:Glycated Hemoglobin; D011135:Polysaccharides, Bacterial; C517652:hemoglobin A1c protein, human
keywords: K. pneumoniae; capsular polysaccharide; diabetes mellitus; glycated hemoglobin; phagocytosis