Genetic and Functional Analysis of the
            <i>pks</i>
            Gene in Clinical Klebsiella pneumoniae Isolates

Luo, Chaoxi; Chen, Y. S.; Hu, Xueyuan; Chen, Shanjian; Lin, Yu; Liu, Xiaoqian; Yang, Bin

doi:10.1128/spectrum.00174-23

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…However, this explanation does not fully account for the increased proteins from the fim operon, indicating the involvement of broader regulatory mechanisms. A recent study has reported a direct correlation between biofilm formation and the colibactin operon in isolates of E. coli and K. pneumoniae 71,72 . Furthermore, since it has been demonstrated that the inactivation of PPK by mutagenesis reduces the promoter activity of clbB (the gene that encodes for an essential enzyme for colistin biosynthesis) and decreases the production level of colibactin 73 , it is possible that the absence of this enzyme also leads to a decrease in biofilm formation through this pathway.…”

Section: Discussionmentioning

confidence: 98%

Effects of Polyphosphate metabolism Mutations on Biofilm, Capsule Formation and Virulence Traits in Hypervirulent ST23Klebsiella pneumoniaeSGH10

Rojas,

Marcoleta,

Gálvez

et al. 2023

Preprint

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The emergence of hypervirulent Klebsiella pneumoniae (hvKP) strains poses a significant threat to public health due to their high mortality rates and propensity to cause severe community-acquired infections in otherwise healthy individuals. The ability of hvKP to form biofilms and produce a protective capsule contributes to its enhanced virulence and is a significant challenge to effective antibiotic treatment. Therefore, understanding the molecular mechanisms underlying hvKP virulence and biofilm formation is crucial for developing new therapeutic strategies. Polyphosphate Kinase 1 (PPK1) is an enzyme responsible for inorganic polyphosphate synthesis and plays a vital role in regulating various physiological processes in bacteria. In this study, we investigated the impact of polyP metabolism on the biofilm and capsule formation and virulence traits in hvKP using Dictyostelium discoideum amoeba as a model host. We found that the PPK1 null-mutant was impaired in biofilm and capsule formation and showed attenuated virulence in D. discoideum compared to the wild-type strain. We performed a shotgun proteomic analysis of the PPK1 mutant and wild-type strain to gain further insight into the underlying molecular mechanism. The results revealed that the PPK1 mutant had a differential expression of proteins (DEP) involved in capsule synthesis (Wzi - Ugd), biofilm formation (MrkC-D-H), synthesis of the colibactin genotoxin precursor (ClbB), as well as proteins associated with the synthesis and modification of lipid A (ArnB -LpxC - PagP). These proteomic findings corroborate the phenotypic observations and indicate that the PPK1 mutation is associated with impaired biofilm and capsule formation and attenuated virulence in hypervirulent K. pneumoniae. Overall, our study highlights the importance of polyP synthesis in regulating extracellular biomolecules and virulence in K. pneumoniae and provides insights into potential therapeutic targets for treating K. pneumoniae infections.

show abstract

Section: Discussionmentioning

confidence: 98%

Effects of Polyphosphate metabolism Mutations on Biofilm, Capsule Formation and Virulence Traits in Hypervirulent ST23Klebsiella pneumoniaeSGH10

Rojas,

Marcoleta,

Gálvez

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…coli and K. pneumoniae. , Furthermore, since it has been demonstrated that the inactivation of PPK by mutagenesis reduces the promoter activity of clbB (the gene that encodes for an essential enzyme for colistin biosynthesis) and decreases the production level of colibactin, it is possible that the absence of this enzyme also leads to a decrease in biofilm formation through this pathway. Recently, a phenotypic switch between type III fimbriae and the hypermucoviscous capsule in response to iron levels has been reported in the SGH10 strain. , The iron-regulated outer membrane protein IroP, encoded in the virulence plasmid, inhibits the expression of the mrk operon under low iron conditions, inhibiting biofilm formation.…”

Section: Discussionmentioning

confidence: 99%

Inorganic Polyphosphate Affects Biofilm Assembly, Capsule Formation, and Virulence of Hypervirulent ST23 Klebsiella pneumoniae

Rojas,

Marcoleta,

Gálvez-Silva

et al. 2024

ACS Infect. Dis.

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The emergence of hypervirulent Klebsiella pneumoniae (hvKP) strains poses a significant threat to public health due to high mortality rates and propensity to cause severe communityacquired infections in healthy individuals. The ability to form biofilms and produce a protective capsule contributes to its enhanced virulence and is a significant challenge to effective antibiotic treatment. Polyphosphate kinase 1 (PPK1) is an enzyme responsible for inorganic polyphosphate synthesis and plays a vital role in regulating various physiological processes in bacteria. In this study, we investigated the impact of polyP metabolism on the biofilm and capsule formation and virulence traits in hvKP using Dictyostelium discoideum amoeba as a model host. We found that the PPK1 null mutant was impaired in biofilm and capsule formation and showed attenuated virulence in D. discoideum compared to the wild-type strain. We performed a proteomic analysis to gain further insights into the underlying molecular mechanism. The results revealed that the PPK1 mutant had a differential expression of proteins involved in capsule synthesis (Wzi-Ugd), biofilm formation (MrkC-D-H), synthesis of the colibactin genotoxin precursor (ClbB), as well as proteins associated with the synthesis and modification of lipid A (ArnB-LpxC-PagP). These proteomic findings corroborate the phenotypic observations and indicate that the PPK1 mutation is associated with impaired biofilm and capsule formation and attenuated virulence in hvKP. Overall, our study highlights the importance of polyP synthesis in regulating extracellular biomolecules and virulence in K. pneumoniae and provides insights into potential therapeutic targets for treating K. pneumoniae infections.

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“…30 Recently, surveys from different areas indicated that the infection of colibactin-producing K. pneumoniae (pks-positive K. pneumoniae) was scaled up rapidly. 31 A patient encountered recurrent infections with CG23-I hvKP. The isolates all have colibactin genes; one of the isolates, with duplication of the initiator tRNAfMet gene, grew faster in a poor nutritional environment and exhibited enhanced virulence.…”

Section: Colibactinmentioning

confidence: 99%

Hypervirulent Klebsiella pneumoniae

Zou

Yang

2021

N Engl J Med

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Hypervirulent Klebsiella pneumoniae (hvKP), especially multidrug-resistant hvKP (MDR-hvKP) infections, are distributed globally, and lead to several outbreaks with high pathogenicity and mortality in immunocompetent individuals. This is usually characterized by a rapidly metastatic spread resulting in multiple pyogenic tissue abscesses. To date, even though the explanation of hypervirulent factors of hvKP has been identified, it still remains to be fully understood. The most common key virulence agents of hvKP included (1) siderophore systems for iron acquisition, (2) increased capsule production, (3) the colibactin toxin, (4) hypermucoviscosity, and so on. Several hypervirulence factors have been renewed, and the evolution of MDR-hvKP has been deeply explored recently. We aim to describe a chain of key virulence agents attributed to the lethality of hvKP and MDR-hvKP. In this review, recent advances in renewed factors in hypervirulence were summarized, and potential therapeutic targets are explored. Novel co-existence of hypervirulence agents and multidrug-resistant elements, even the superplasmid, was screened. Superplasmid simultaneously harbours hypervirulence and multidrug-resistant genes and can mobile autonomously by its complete conjugative elements. Research into related immunity has also gained traction, which may cause multiple invasive infections with higher mortality rates than classical ones, such as neutrophil-and complement-mediated activity. The evolution of virulence and multidrug resistance is accelerating. More reliable methods for identifying hvKP or MDR-hvKP must be investigated. Furthermore, it is critical to investigate innovative treatment targets in the future.

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Genetic and Functional Analysis of the pks Gene in Clinical Klebsiella pneumoniae Isolates

Cited by 5 publications

References 30 publications

Effects of Polyphosphate metabolism Mutations on Biofilm, Capsule Formation and Virulence Traits in Hypervirulent ST23Klebsiella pneumoniaeSGH10

Effects of Polyphosphate metabolism Mutations on Biofilm, Capsule Formation and Virulence Traits in Hypervirulent ST23Klebsiella pneumoniaeSGH10

Inorganic Polyphosphate Affects Biofilm Assembly, Capsule Formation, and Virulence of Hypervirulent ST23 Klebsiella pneumoniae

Hypervirulent Klebsiella pneumoniae

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