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Title: Mycobacterium hassiacum recovers from nitrogen starvation with up-regulation of a novel glucosylglycerate hydrolase and depletion of the accumulated glucosylglycerate
Authors: Alarico, Susana 
Costa, Maria Mafalda Santos 
Sousa, Marta S. 
Maranha, Ana 
Lourenço, Eva C.
Faria, Tiago Q. 
Ventura, M. Rita
Empadinhas, Nuno 
Issue Date: 24-Oct-2014
Publisher: Springer Nature
Project: We are grateful to the Mizutani Foundation for Glycoscience, Japan, for financial support through the Exploratory Grant 120123. We thank Dr. Igor Tiago for invaluable support on the construction and analysis of the phylogenetic tree. This work was supported by national funds through Fundaça˜o para a Cieˆncia e a Tecnologia (FCT) and by EU-FEDER funding through the Operational Competitiveness Programme – COMPETE (Grants FCOMP-01-0124-FEDER-014321 [PTDC/BIA-PRO/110523/2009], FCOMP-01-0124-FEDER-028359 [PTDC/BIA-MIC/2779/2012], and FCOMP-01-0124-FEDER-037276 [PEst-C/SAU/LA0001/2013-2014]. S. Alarico, A. Maranha and E. C. Lourenço acknowledge FCT fellowships SFRH/BPD/43321/2008 and SFRH/BD/74845/2010 and SFRH//BD/47702/2008. 
Serial title, monograph or event: Scientific Reports
Volume: 4
Issue: 1
Abstract: Some microorganisms accumulate glucosylglycerate (GG) during growth under nitrogen deprivation. However, the molecular mechanisms underlying the role of GG and the regulation of its levels in the nitrogen stress response are elusive. Since GG is required for biosynthesis of mycobacterial methylglucose lipopolysaccharides (MGLP) we examined the molecular mechanisms linking replenishment of assimilable nitrogen to nitrogen-starved M. hassiacum with depletion of GG accumulated during nitrogen deficiency. To probe the involvement of a newly identified glycoside hydrolase in GG depletion, we produced the mycobacterial enzyme recombinantly and confirmed the specific hydrolysis of GG (GG hydrolase, GgH) in vitro. We have also observed a pronounced up-regulation of GgH mRNA in response to the nitrogen shock, which positively correlates with GG depletion in vivo and growth stimulation, implicating GgH in the recovery process. Since GgH orthologs seem to be absent from most slowly-growing mycobacteria including M. tuberculosis, the disclosure of the GgH function allows reconfiguration of the MGLP pathway in rapidly-growing species and accommodation of this possible regulatory step. This new link between GG metabolism, MGLP biosynthesis and recovery from nitrogen stress furthers our knowledge on the mycobacterial strategies to endure a frequent stress faced in some environments and during long-term infection.
ISSN: 2045-2322
DOI: 10.1038/srep06766
Rights: openAccess
Appears in Collections:IIIUC - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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