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Identified Virulence Factors of Francisella : Metabolic adaptation


AnsP  

Related genes: ansP;
Keywords: Metabolic adaptation;
Characteristics:
Belongs to the Phagosomal transporter (Pht) subclass of major facilitator superfamily that is exclusively found among intracellular pathogenic bacteria
Functions:
AnsP permease contributes to bacterial multiplication by providing asparagine for protein synthesis
References:
Gesbert G, et al., 2014. Asparagine assimilation is critical for intracellular replication and dissemination of Francisella. Cell Microbiol 16(3):434-49.


ArgP  

Related genes: argP;
Keywords: Metabolic adaptation;
Characteristics:
ArgP is the closest paralogue of Francisella GadC within the APC (amino acid-polyamine-organocation) family of transporter
Functions:
High affinity arginine transporter mediating arginine uptake that is crucial for efficient phagosomal escape
References:
Ramond E, et al., 2015. Importance of host cell arginine uptake in Francisella phagosomal escape and ribosomal protein amounts. Mol Cell Proteomics 14(4):870-81.


Biotin synthesis  

Related genes: bioA; bioB; bioC; bioD; bioF; bioJ; bplA;
Keywords: Metabolic adaptation;
Characteristics:
Biotin is an important enzyme cofactor that acts as a covalently bound prosthetic group
Biotin plays critical roles in central metabolic processes involving carboxylation, decarboxylation and transcarboxylation
F. novicida has evolved two distinct biotin protein ligases BplA and BirA with specific roles. Only BplA is required for pathogenicity
Figures:
Genetic organization of biotin synthesis-related genes and working model for the Francisella biotin biosynthesis pathway. (From: Feng Y, et al., 2014. A Francisella virulence factor catalyses an essential reaction of biotin synthesis. Mol Microbiol 91(2):300-14.)

Functions:
Critical for rapid phagosomal escape. Sequestration of biotin could restrict Francisella to the phagosome, blocking their escape and preventing them from reaching their replicative niche in the cytoplasm
References:
Napier BA, et al., 2012. Link between intraphagosomal biotin and rapid phagosomal escape in Francisella. Proc Natl Acad Sci U S A 109(44):18084-9.
Feng Y, et al., 2014. A Francisella virulence factor catalyses an essential reaction of biotin synthesis. Mol Microbiol 91(2):300-14.
Feng Y, et al., 2015. The Atypical Occurrence of Two Biotin Protein Ligases in Francisella novicida Is Due to Distinct Roles in Virulence and Biotin Metabolism. MBio 6(3):e00591.


GadC  

Related genes: gadC;
Keywords: Metabolic adaptation;
Functions:
Glutamate permease GadC helps the bacterium to resist the oxidative stress generated by the NADPH oxidase.This transporter is critically required for proper bacterial phagosomal escape
References:
Ramond E, et al., 2014. Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape. PLoS Pathog 10(1):e1003893.


GGT (γ-glutamyl transpeptidase)  

Related genes: ggt;
Keywords: Metabolic adaptation;
Functions:
Cleavage of cysteine containing peptides (glutathione and γ-glutamyl-cysteine peptides) by GGT activity thus provides the essential source of cysteine required for intracellular multiplication
References:
Alkhuder K, et al., 2009. Glutathione provides a source of cysteine essential for intracellular multiplication of Francisella tularensis. PLoS Pathog 5(1):e1000284.


IleP  

Related genes: ileP;
Keywords: Metabolic adaptation;
Characteristics:
Belongs to the Phagosomal transporter (Pht) subclass of major facilitator superfamily that is exclusively found among intracellular pathogenic bacteria
Functions:
Mediating isoleucine uptake tha is vital for bacterial intracellular multiplication and virulence
References:
Gesbert G, et al., 2015. Importance of branched-chain amino acid utilization in Francisella intracellular adaptation. Infect Immun 83(1):173-83.


Purine biosynthesis  

Related genes: purCD; purM;
Keywords: Metabolic adaptation;
Characteristics:
The purMCD locus encodes three enzymes (phosphoribosylaminoimidazol synthetase, SAICAR synthetase, and phosphoribosylamine-glycine ligase) required for the de novo synthesis of purine nucleotides.
Functions:
Required for bacterial cytosolic replication
References:
Pechous R, et al., 2006. Construction and characterization of an attenuated purine auxotroph in a Francisella tularensis live vaccine strain. Infect Immun 74(8):4452-61.
Pechous RD, et al., 2008. A Francisella tularensis Schu S4 purine auxotroph is highly attenuated in mice but offers limited protection against homologous intranasal challenge. PLoS One 3(6):e2487.


Pyrimidine biosynthesis  

Related genes: carA; carB; pyrB;
Keywords: Metabolic adaptation;
Characteristics:
CarB, CarA, and PyrB encode the large and small subunits of carbamoylphosphate synthetase and aspartate carbamoyl transferase, respectively. These enzymes catalyze the first two steps in the pyrimidine nucleotide biosynthetic pathway in many bacteria, including Francisella, and are required for the virulence of several pathogens, including Salmonella and E. coli
Functions:
Mediating bacterial resistance to reactive oxygen species (ROS) that is important for phagosomal escape
References:
Schulert GS, et al., 2009. Francisella tularensis genes required for inhibition of the neutrophil respiratory burst and intramacrophage growth identified by random transposon mutagenesis of strain LVS. Infect Immun 77(4):1324-36.








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