Targeting protein tyrosine phosphatases for the development of antivirulence agents: Yersinia spp. and Mycobacterium tuberculosis as prototypes

Protein phosphorylation mediated by protein kinases and phosphatases has a central regulatory function in many cellular processes in eukaryotes and prokaryotes. As a result, several diseases caused by imbalance in phosphorylation levels are known, especially due to protein tyrosine phosphatases (PTP...

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Published in:Biochimica et biophysica acta. Proteins and proteomics 2022-05, Vol.1870 (5), p.140782-140782, Article 140782
Main Author: Menegatti, Angela Camila Orbem
Format: Article
Language:English
Subjects:
Antimicrobial resistance
Antivirulence strategy
Drug Design
Enzyme Inhibitors
Inhibition
Mycobacterium tuberculosis
Protein Tyrosine Phosphatases
PTP
Yersinia - metabolism
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Summary:Protein phosphorylation mediated by protein kinases and phosphatases has a central regulatory function in many cellular processes in eukaryotes and prokaryotes. As a result, several diseases caused by imbalance in phosphorylation levels are known, especially due to protein tyrosine phosphatases (PTPs) activity, an important family of signaling enzymes. Furthermore, over the last decades several studies have shown the main role of PTPs in pathogenic bacteria: they are associated with growth, cell division, cell wall biosynthesis, biofilm formation, metabolic processes, as well as virulence factor. In this way, PTPs have ascended as targets for antibacterial drug design, particularly in view of the antibiotic resistance in pathogenic bacteria, which demands novel therapeutics strategies. Targeting secreted PTPs is an antivirulence strategy to combat the emergence of antimicrobial resistance (AMR). This review focuses on the recent advances in understanding the role of PTPs and the approaches to target them, with an emphasis in Yersinia spp. and Mycobacterium tuberculosis pathogenesis. [Display omitted] •Antivirulence is a promising strategy to combat antimicrobial resistance.•Antivirulence agents do not target bacterial growth pathways, they target virulence factors.•Protein tyrosine phosphatases (PTPs) are key virulence factors in many pathogens.•Mycobacterium tuberculosis and Yersinia secreted PTPs are required for bacterial survival within host.•Bacterial PTPs are attractive targets for drug development.
ISSN:1570-9639
1878-1454
DOI:10.1016/j.bbapap.2022.140782