Rv2577 of Mycobacterium tuberculosis Is a Virulence Factor With Dual Phosphatase and Phosphodiesterase Functions

Frontiers in Microbiology
Marina Andrea ForrelladF Bigi

Abstract

Tuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), is one of the ten leading causes of death worldwide affecting mainly developing countries. Mtb can persist and survive inside infected cells through modulation of host antibacterial attack, i.e., by avoiding the maturation of phagosome containing mycobacteria to more acidic endosomal compartment. In addition, bacterial phosphatases play a central role in the interplay between host cells and Mtb. In this study, we characterized the Rv2577 of Mtb as a potential alkaline phosphatase/phosphodiesterase enzyme. By an in vitro kinetic assay, we demonstrated that purified Rv2577 expressed in Mycobacterium smegmatis displays both enzyme activities, as evidenced by using the artificial substrates p-NPP and bis-(p-NPP). In addition, a three-dimensional model of Rv2577 allowed us to define the catalytic amino acid residues of the active site, which were confirmed by site-directed mutagenesis and enzyme activity analysis, being characteristic of a member of the metallophosphatase superfamily. Finally, a mutation introduced in Rv2577 reduced the replication of Mtb in mouse organs and impaired the arrest of phagosomes containing mycobacteria in early endosomes; which ind...Continue Reading

References

Oct 9, 2002·Microbiology·María P SantangeloFabiana Bigi
Nov 18, 2003·Molecular Microbiology·Ramandeep SinghAnil K Tyagi
Dec 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Gerhard SchenkLuke W Guddat
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Jul 14, 2009·Microbes and Infection·Federico C BlancoFabiana Bigi
Nov 17, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dennis WongYossef Av-Gay
Oct 19, 2012·Virulence·Marina A ForrelladFabiana Bigi
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Jan 21, 2014·Tuberculosis·Marina Andrea ForrelladFabiana Bigi
Aug 12, 2014·Cold Spring Harbor Perspectives in Medicine·Mary Jackson
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Nov 6, 2018·Nucleic Acids Research·Yasset Perez-RiverolJuan Antonio Vizcaíno

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Datasets Mentioned

BETA
PXD019769

Methods Mentioned

BETA
glycosylation
PCR
confocal microscopy
PMA

Software Mentioned

BLASTp
Patternlab
ExPASy
PROSITE
GraphPad Prism
ConSurf
GraphPad Prim
Fiji
tasser
COACH

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