Finding of the Low Molecular Weight Inhibitors of Resuscitation Promoting Factor Enzymatic and Resuscitation Activity

@article{Demina2009FindingOT,
  title={Finding of the Low Molecular Weight Inhibitors of Resuscitation Promoting Factor Enzymatic and Resuscitation Activity},
  author={G. Demina and V. Makarov and V. Nikitushkin and O. Ryabova and G. Vostroknutova and E. Salina and M. Shleeva and A. Goncharenko and A. Kaprelyants},
  journal={PLoS ONE},
  year={2009},
  volume={4}
}
Background Resuscitation promoting factors (RPF) are secreted proteins involved in reactivation of dormant actinobacteria, including Mycobacterium tuberculosis. They have been considered as prospective targets for the development of new anti-tuberculosis drugs preventing reactivation of dormant tubercle bacilli, generally associated with latent tuberculosis. However, no inhibitors of Rpf activity have been reported so far. The goal of this study was to find low molecular weight compounds… Expand
Resuscitation Promoting Factors: a Family of Microbial Proteins in Survival and Resuscitation of Dormant Mycobacteria
TLDR
Molecular and structural studies conducted on Rpf proteins, their role in the resuscitation of dormant bacteria, in the reactivation of latent infection and identification of low molecular weight inhibitors of resuscitation promoting factors are described. Expand
Molecular determinants of inactivation of the resuscitation promoting factor B from Mycobacterium tuberculosis
TLDR
It is proved that the substitution of 4-benzoyl-2-nitrophenyl thiocyanate group of NPT7 implies a complete loss of RpfB inactivation, with the final aim of developing second-generation inhibitors of therapeutic interest in TB eradication strategy. Expand
Resuscitation-promoting factors (Rpf): in search of inhibitors.
TLDR
Recent progress in understanding of molecular mechanisms of Rpf biological activity is described and recently characterised nitrophenylthiocyanate compounds could be considered as a promising scaffold for generation of therapeutic agents targeting reactivation of latent tuberculosis. Expand
Defining New Drug Targets Through Protein-Protein Interaction: Interaction of Resuscitation Promoting Factors with SucA of TCA Cycle in M. tuberculosis H37Rv
TLDR
It is hypothesized that during transition from nonculturable to resuscitation phase mycobacteria cleaves its hard breaking cell wall by endopeptidase RipA interacting with Rpf B and increases its metabolic energy generation by evoking TCA cycle and could serve as prospective target along with R pfs and RipA for development of new anti-tuberculosis drugs preventing reactivation of dormant bacilli. Expand
Computational investigation of phytomolecules as resuscitation-promoting factor B (RpfB) inhibitors for clinical suppression of Mycobacterium tuberculosis dormancy reactivation.
TLDR
The findings of this study indicated that phytomolecules are capable to efficiently inhibit the RpfB, which is vital for reactivation of dormant Mtb. Expand
Rpf proteins are the factors of reactivation of the dormant forms of actinobacteria
TLDR
The unique ability of Rpf proteins to resuscitate the dormant forms of mycobacteria and to stimulate their proliferation would allow these proteins to occupy their niche in medicine–in diagnostics and in creation of antituberculosis subunit vaccines. Expand
Elucidating the enzymatic function of resuscitation promoting factor B, RpfB, from Mycobacterium tuberculosis
ELUCIDATING THE ENZYMATIC FUNCTION OF RESUSCITATION PROMOTING FACTOR B, RPFB, FROM MYCOBACTERIUM TUBERCULOSIS Jonathan Joseph Samson Advisor: University of Guelph, 2015 Professor A. J. Clarke TheExpand
Benzoylphenyl thiocyanates are new, effective inhibitors of the mycobacterial resuscitation promoting factor B protein
TLDR
P dispensability of the nitro group in the NPT’s structure for inhibition of the enzymatic and biological activities of the Rpf protein molecules is demonstrated. Expand
Peptidoglycan fragments stimulate resuscitation of “non-culturable” mycobacteria
TLDR
It was observed that PG-dependent resuscitation activity was suppressed by means of a specific Rpf inhibitor (4-benzoyl-2-nitrophenylthiocyanate), which provides additional support for the second of these possibilities. Expand
Protective and therapeutic effects of the resuscitation-promoting factor domain and its mutants against Mycobacterium tuberculosis in mice.
TLDR
It is demonstrated that replacement of E54 by different amino acids in RpFD distinctively influenced its resuscitation-promoting activities and Th1-type immune responses induced in mice, suggesting Rpfd2 as a novel effective vaccine candidate against Mtb. Expand
...
1
2
3
4
...

References

SHOWING 1-10 OF 40 REFERENCES
A family of autocrine growth factors in Mycobacterium tuberculosis
TLDR
It is shown here that the five cognate proteins from M. tuberculosis have very similar characteristics and properties to those of Rpf, and may provide novel opportunities for preventing and controlling mycobacterial infections. Expand
Proteins of the Rpf (resuscitation promoting factor) family are peptidoglycan hydrolases
TLDR
The data indicate that Rpf is a peptidoglycan-hydrolyzing enzyme, and strongly suggest that this specific activity is responsible for its growth promotion and resuscitation activity. Expand
The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro
TLDR
Results from this study are indicative of a hierarchy in terms of function and/or potency with the Rpf family, with R pfB and rpfE ranking above Rp fD, with the latter persisting better than the former in late‐stage infection. Expand
The structure of a resuscitation-promoting factor domain from Mycobacterium tuberculosis shows homology to lysozymes
TLDR
Biochemical studies and solution structure data indicate that a conserved active site glutamate is important for resuscitation activity, and indicate that oligosaccharide cleavage is probably the signal for revival from dormancy. Expand
Resuscitation factors from mycobacteria: homologs of Micrococcus luteus proteins.
TLDR
The mycobacterial Rpfs demonstrate resuscitation activities similar to those of the M. luteus Rpf and promoted recovery of extensively washed Mycobacterium smegmatis bacteria inoculated into Sauton medium. Expand
The role of resuscitation promoting factors in pathogenesis and reactivation of Mycobacterium tuberculosis during intra-peritoneal infection in mice
TLDR
An intraperitoneal infection model in mice is developed that models chronic infection with similar properties in mouse lungs as those observed in the murine aerosol infection model and finds that rpf proteins may have a significant physiological role for development of chronic TB infection and its reactivation in vivo. Expand
Muralytic activity of Micrococcus luteus Rpf and its relationship to physiological activity in promoting bacterial growth and resuscitation
TLDR
The muralytic activities of the Rpf mutants were correlated with their abilities to stimulate bacterial culturability and resuscitation, consistent with the view that the biological activity of RpF results directly or indirectly from its ability to cleave bonds in bacterial peptidoglycan. Expand
A bacterial cytokine.
TLDR
A proteinaceous autocrine or paracrine bacterial growth factor or cytokine, which promotes the resuscitation and growth of dormant, nongrowing cells of the same organism, is described. Expand
Crystal structure of the resuscitation-promoting factor (DeltaDUF)RpfB from M. tuberculosis.
TLDR
Interestingly, sequence comparisons indicate that these structural features are also shared by G5 domains involved in biofilm formation, which suggests that the RpfB G5 domain has a cell-wall adhesive function, which allows the catalytic domain to be properly oriented for the cleavage reaction. Expand
The rpf gene of Micrococcus luteus encodes an essential secreted growth factor
TLDR
Rpf is the first example of a truly secreted protein that is essential for bacterial growth, and if the Rpf‐like proteins elaborated by Mycobacterium tuberculosis and other mycobacteria prove similarly essential, interference with their proper functioning may offer novel opportunities for protecting against, and treating, tuberculosis. Expand
...
1
2
3
4
...