Cyclic AMP-CRP Modulates the Cell Morphology of Klebsiella pneumoniae in High-Glucose Environment

Liu, Long; Li, Feiyu; Xu, Li; Wang, Jingjie; Li, Yaqian; Yuan, Jing; Wang, Hui; Yang, Ruiping; Li, Bei

doi:10.3389/fmicb.2019.02984

Cited by 12 publications

(12 citation statements)

References 52 publications

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“…Further, CRP has been implicated in the regulation of multiple stress and virulence factors, together with antibiotic resistance. 53–55 , 63–65 Using an isogenic Δ crp mutant we could not observe, at least in the tested experimental conditions, any role for this gene in modulating fitness in an immune-activated scenario; however, we report that crp is per se crucial to establish colonization of the gut in the first place. This is in keeping with our failure to detect glucose in the mouse intestine via metabolomics approaches.…”

Section: Discussioncontrasting

confidence: 58%

Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation

David,

Czauderna,

Cheng

et al. 2024

Gut Microbes

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Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is a significant threat to public health worldwide. The primary reservoir for CR-Kp is the intestinal tract. There, the bacterium is usually present at low density but can bloom following antibiotic treatment, mostly in hospital settings. The impact of disturbances in the intestinal environment on the fitness, survival, expansion, and drug susceptibility of this pathogen is not well-understood, yet it may be relevant to devise strategies to tackle CR-Kp colonization and infection. Here, we adopted an in vivo model to examine the transcriptional adaptation of a CR-Kp clinical isolate to immune activation in the intestine. We report that as early as 6 hours following host treatment with anti-CD3 antibody, CR-Kp underwent rapid transcriptional changes including downregulation of genes involved in sugar utilization and amino acid biosynthesis and upregulation of genes involved in amino acid uptake and catabolism, antibiotic resistance, and stress response. In agreement with these findings, treatment increased the concentration of oxidative species and amino acids in the mouse intestine. Genes encoding for proteins containing the domain of unknown function (DUF) 1471 were strongly upregulated, however their deletion did not impair CR-Kp fitness i n vivo upon immune activation. Transcription factor enrichment analysis identified the global regulator cAMP-Receptor Protein, CRP, as a potential orchestrator of the observed transcriptional signature. In keeping with the recognized role of CRP in regulating utilization of alternative carbon sources, crp deletion in CR-Kp resulted in strongly impaired gut colonization, although this effect was not amplified by immune activation. Thus, following intestinal colonization, which occurs in a CRP-dependent manner, CR-Kp can rapidly respond to immune cues by implementing a well-defined and complex transcriptional program whose direct relevance toward bacterial fitness warrants further investigation. Additional analyses utilizing this model may identify key factors to tackle CR-Kp colonization of the intestine.

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Section: Discussioncontrasting

confidence: 58%

Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation

David,

Czauderna,

Cheng

et al. 2024

Gut Microbes

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“…Studies of a strain of K. pneumoniae strain NTUH-K2044 showed that the mutant with the Δcrp deletion was characterized by increased HMV and ability to form biofilms and produce fimbriae [76,98]. Excess glucose in the external environment decreased the CRP level, leading to increased cps gene expression [79].…”

Section: Hypermucoviscosity and Regulators Of Capsule Synthesismentioning

confidence: 99%

Molecular Epidemiology of Hypervirulent K. pneumoniae and Problems of Health-Care Associated Infections

et al. 2022

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The review describes virulence factors of hypervirulent K. pneumoniae (hvKp) including genes determining its virulence and discusses their role in the development of health-care associated infections. The contribution of individual virulence factors and their combination to the development of the hypervirulence and the prospects of using these factors as biomarkers and therapeutic targets are described. Virulence factors of hvKp and “classical” K. pneumoniae strains (cKp) with no hypervirulence genes were compared. The mechanisms of biofilm formation by hvKp and high incidence of its antibiotic resistance are of particular importance for in health care institutions. Therefore, the development of methods for hvKp identification allowing early prevention of severe hvKp infection and novel approaches to abrogate its spreading are new challenges for epidemiology, infection diseases, and critical care medicine. New technologies including bacteriological and molecular studies make it possible to develop innovative strategies to diagnose and treat infection caused by hvKp. These include monitoring of both genetic biomarkers of hvKp and resistance plasmid that carry of virulence genes and antibiotic resistance genes, creation of immunological agents for the prevention and therapy of hvKp (vaccines, monoclonal antibodies) as well as personalized hvKp-specific phage therapies and pharmaceuticals enhancing the effect of antibiotics. A variety of approaches can reliably prepare our medicine for a new challenge: spreading of life-threatening health-care associated infections caused by antibiotic-resistant hvKp strains.

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“…However, there was no significant difference in the level of transcription in the high-glucose environment. 35 Therefore, the regulation of ompA by high glucose is still controversial. This investigation revealed that high glucose enhanced the mRNA of ompA and the addition of exogenous cAMP suppressed its enhancement.…”

Section: Discussionmentioning

confidence: 99%

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

Tang¹,

Wang²,

Cao³

et al. 2023

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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.

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Cyclic AMP-CRP Modulates the Cell Morphology of Klebsiella pneumoniae in High-Glucose Environment

Cited by 12 publications

References 52 publications

Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation

Intestinal carbapenem-resistant Klebsiella pneumoniae undergoes complex transcriptional reprogramming following immune activation

Molecular Epidemiology of Hypervirulent K. pneumoniae and Problems of Health-Care Associated Infections

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

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