Epidemiological Features and Impact of High Glucose Level on Virulence Gene Expression and Serum Resistance of Klebsiella pneumoniae Causing Liver Abscess in Diabetic Patients

Abstract

Purpose Klebsiella pneumoniae ( K. pneumoniae ) is a Gram-negative bacterium that is predominantly associated with liver abscesses in global diabetic patients. High levels of glucose in the surrounding of K. pneumonia increase its pathogenicity including capsular polysaccharide (CPS) and fimbriae. Other important virulent factors include outer membrane protein A (ompA) and regulator mucoid phenotype A (rmpA). The objective of this investigation was to elucidate the effects of high glucose on rmpA and ompA gene expression and serum resistance of K. pneumoniae causing liver abscess. Patients and Methods The clinical history of 57 patients suffering from K. pneumoniae -caused liver abscesses (KLA) was acquired and their clinical and laboratory manifestations in the presence or absence of diabetes were analyzed. The antimicrobial susceptibility, serotypes, and virulence genes were tested. Clinical isolates of 3 serotype-K1 hypervirulent K. pneumoniae (hvKP) were used to detect the effect of exogenous high glucose on rmpA, ompA , and clbB genes expression, and bacterial serum resistance. Results KLA patients with diabetes showed higher C-reactive protein (CRP) compared to non-diabetic KLA patients. Furthermore, the diabetic group showed increased incidences of sepsis and invasive infections, and their length of hospital stay was also prolonged. Pre-incubation of K. pneumoniae in high glucose (0.5%) concentration up-regulated rmpA, ompA , and clbB genes expression. However, cAMP supplementation, which was inhibited by environmental glucose, reversed the increase of rmpA and ompA in a cAMP-dependent manner. Moreover, hvKP strains incubated in high glucose also exhibited enhanced protection from serum killing. Conclusion High glucose levels reflected by poor glycemic control has increased gene expression of rmpA and ompA in hvKP by the cAMP signaling pathway and enhanced its resistance to serum killing, thus providing a new and reasonable explanation for the high incidences of sepsis and invasive infections in KLA patients with diabetes.

The causal relationship between bacterial pneumonia and diabetes: a two-sample mendelian randomization study

“…Consequently, this upregulation contributes to enhanced resistance against the immune system via the cAMP signaling pathway. 14 These observational studies provide preliminary evidence on potential exposure factors associated with bacterial pneumonia in individuals with diabetes. In previous observational studies, the presence of reverse causality has posed a challenge, rendering it arduous to ascertain a causal association between bacterial pneumonia and diabetes.…”

Long Term Characteristics of Clinical Distribution and Resistance Trends of Carbapenem-Resistant and Extended-Spectrum β-Lactamase Klebsiella pneumoniae Infections: 2014–2022 [Response to Letter]

“…It has been reported that carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has caused fatal hospital infection. 3 And hyperglycemia increases the gene expression of RmpA and ompA in hvKP through cAMP signaling pathway, 4 which will increase the cost of treatment and extend the length of hospital stay.…”

Demographics and prognosis of patients with pyogenic liver abscess due to Klebsiella pneumonia or other species

“…However, the prevalence of PLA from Klebsiella pneumoniae (KP) infection has increased significantly in China and Southeast Asia during recent years, and several studies reported that KP accounted for more than half of the positive culture results in Asian patients with PLA [ [4] , [5] , [6] ]. It is now believed that this significantly higher proportion of cases with KP pyogenic liver abscess (KPPLA) is related to improvements in pathogenic testing, increased susceptibility to KP infection, and the increased incidence of diabetes mellitus [ 7 ].…”

“…The use of effective antibiotic therapies, improvements in diagnostic imaging, and adoption of less invasive interventions, especially the widespread application of percutaneous needle aspiration (PNA) and pigtail catheter drainage (PCD), have reduced the mortality rate of patients with PLA, and it is now only about 6–14 % [ 1 , 8 ]. However, liver abscesses caused by KP infections are prone to invasive liver abscess syndrome, and infections by hypervirulent KP (hvKP) and the emergence of drug-resistant KP have dramatically increased the hospitalization costs and mortality of patients with PLA [ 7 , 9 ]. Some studies showed that PLA caused by other pathogens is relatively uncommon in China, although there have been no direct and extensive comparisons between the KPPLA and non- Klebsiella pneumoniae pyogenic liver abscess (non-KPPLA) in the Chinese population [ 4 , 10 , 11 ].…”