Polyphosphate Kinase Is Required for the Processes of Virulence and Persistence in Acinetobacter baumannii

Lv, Hongfa; Zhou, Yonglin; Liu, Baichen; Guan, Jian; Zhang, Peng; Deng, Xuming; Li, Dan; Wang, Jianfeng

doi:10.1128/spectrum.01230-22

Cited by 11 publications

(12 citation statements)

References 42 publications

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“…The Δ ppk1 and Δ ppk1 -Δ ppx mutants exhibited reduced biofilm formation compared to the WT strain. These results are consistent with previous reports in various models 28,66–69 . Interestingly, the use of mesalamine, a drug used in the treatment of ulcerative colitis that also inhibits PPK1 30 , showed similar levels of biomass reduction in the biofilm as observed in Δ ppk1 and Δ ppk1 -Δ ppx mutant cells, confirming the close association between biofilm formation and polyphosphates.…”

Section: Discussionsupporting

confidence: 94%

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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.

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Section: Discussionsupporting

confidence: 94%

“…S2B). PPK1 is the main enzyme responsible for synthesizing polyP in bacterial models such as P. aeruginosa and Acinetobacter baumannii 23,28 . However, its role in K. pneumoniae has not been extensively studied.…”

Section: Deleting Polyp Metabolism Genes Does Not Affect Viability An...mentioning

confidence: 99%

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

“…PPK1 is the main enzyme responsible for synthesizing polyP in bacterial models such as P. aeruginosa and Acinetobacter baumannii. , However, its role in K. pneumoniae has not been extensively studied.…”

Section: Resultsmentioning

confidence: 99%

“…PPK1 is the main enzyme responsible for synthesizing polyP in bacterial models such as P. aeruginosa and Acinetobacter baumannii. 24,28 However, its role in K. pneumoniae has not been extensively studied. Nutrient deprivation is a known condition that promotes the accumulation of polyP in bacteria.…”

Section: Mutants Lacking Genes Involved In Polyp Synthesis and Degrad...mentioning

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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“…In other pathogenic bacteria, it has been suggested that the production of storage compounds affects virulence. − This, together with the increased ROS sensitivity of the Δwax/dgat::kanR mutant, prompted us to analyze the effect of the absence of WS/DGAT on the survival of Galleria mellonella . Therefore, we grew the A. baumannii wild type and the Δwax/dgat::kanR mutant in the presence or absence of nitrogen limitation and used these cultures to infect G. mellonella .…”

Section: Resultsmentioning

confidence: 99%

Wax Ester and Triacylglycerol Production in Acinetobacter baumannii: Role in Osmostress Protection, Reactive Oxygen Species, and Antibiotic Sensitivity

Pfefferle,

Averhoff

2023

ACS Infect. Dis.

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Wax esters (WEs) are neutral lipids that are produced by many different bacteria as potential carbon and energy storage compounds. Comparatively little is known about the role of WE in pathogenic bacteria. The opportunistic pathogen Acinetobacter baumannii is a major cause of hospital-acquired infections worldwide. Salt and desiccation resistance foster A. baumannii infections such as urinary tract infections and allow for reinfection when bacteria are taken up from dry surfaces in the hospital environment. Here we report on WE and triacylglycerol (TAG) production in A. baumannii as a response to nitrogen limitation and high salt stress. Fatty acids and fatty alcohols with chain lengths of C16 and C18 were identified as the most prominent WE constituents. We identified the terminal key enzyme of WE biosynthesis, the bifunctional wax ester synthase/acylCoA:diacylglycerol acyltransferase (WS/DGAT) encoded by the wax/dgat gene, and demonstrated that transcription of wax/dgat and production of WS/DGAT are independent of the nitrogen concentration. A Δwax/dgat mutant was impaired in growth in the presence of high salt concentration and was more sensitive to imipenem and reactive oxygen species.

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Polyphosphate Kinase Is Required for the Processes of Virulence and Persistence in Acinetobacter baumannii

Abstract: A. baumannii was identified as a top-priority pathogen by the WHO due to its antibiotic resistance. Meanwhile, the pathogenicity of A. baumannii mediated by several vital virulence factors also cannot be ignored.

Cited by 11 publications

References 42 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

Wax Ester and Triacylglycerol Production in Acinetobacter baumannii: Role in Osmostress Protection, Reactive Oxygen Species, and Antibiotic Sensitivity

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