Dataset Information

Accumulation of inorganic polyphosphate mediates metabolic downshift and antibiotic tolerance in Mycobacterium tuberculosis

ABSTRACT: The stringent response, involving the regulatory molecules inorganic polyphosphate (poly P) and (p)ppGpp, is believed to mediate Mycobacterium tuberculosis persistence. In this study, we identified a novel exopolyphosphatase responsible for poly P hydrolysis. Using two different poly P-accumulating M. tuberculosis recombinant strains, we found that increased poly P content drives the organisms into early growth arrest, and contributes to tolerance to the cell wall-active agent isoniazid, increased resistance to stress conditions, and improved survival in macrophages. Transcriptomic and metabolomics analysis revealed metabolic downshift manifested by reduced expression of the transcriptional and translational machinery, and shift from utilization of glucose as a carbon source. In summary, regulation of the poly P balance is critical for persister formation in M. tuberculosis.

ORGANISM(S): Mycobacterium tuberculosis CDC1551

PROVIDER: GSE57868 | GEO | 2015/02/20

SECONDARY ACCESSION(S): PRJNA248293

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description: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.

Dataset Information

Accumulation of inorganic polyphosphate mediates metabolic downshift and antibiotic tolerance in Mycobacterium tuberculosis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets