Details

Autor(en) / Beteiligte

• Pitzer, Joshua E
• Zeczycki, Tonya N
• Baumgartner, John E
• Martin, Daniel W
• Roop, 2nd, R Martin
• O’Toole, George

Titel

The Manganese-Dependent Pyruvate Kinase PykM Is Required for Wild-Type Glucose Utilization by Brucella abortus 2308 and Its Virulence in C57BL/6 Mice

Ist Teil von

• Journal of bacteriology, 2018-12, Vol.200 (24)

Ort / Verlag

United States: American Society for Microbiology

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Pyruvate kinase plays a central role in glucose catabolism in bacteria, and efficient utilization of this hexose has been linked to the virulence of strains in mice. The brucellae produce a single pyruvate kinase which is an ortholog of the manganese (Mn)-dependent pyruvate kinase PykM. A biochemical analysis of the pyruvate kinase and phenotypic analysis of a mutant defective in high-affinity Mn import indicate that this enzyme is an authentic PykM ortholog which functions as a Mn-dependent enzyme The loss of PykM has a negative impact on the capacity of the parental 2308 strain to utilize glucose, fructose, and galactose but not on its ability to utilize ribose, xylose, arabinose, or erythritol, and a mutant displays significant attenuation in C57BL/6 mice. Although the enzyme pyruvate phosphate dikinase (PpdK) can substitute for the loss of pyruvate kinase in some bacteria and is also an important virulence determinant in , a phenotypic analysis of 2308 and isogenic , , and mutants indicates that PykM and PpdK make distinctly different contributions to carbon metabolism and virulence in these bacteria. Mn plays a critical role in the physiology and virulence of strains, and the results presented here suggest that one of the important roles that the high-affinity Mn importer MntH plays in the pathogenesis of these strains is supporting the function of the Mn-dependent kinase PykM. A better understanding of how the brucellae adapt their physiology and metabolism to sustain their intracellular persistence in host macrophages will provide knowledge that can be used to design improved strategies for preventing and treating brucellosis, a disease that has a significant impact on both the veterinary and public health communities worldwide.