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Lactate dehydrogenase is the key enzyme for pneumococcal pyruvate metabolism and
pneumococcal survival in blood
#MMPMID25245810
Gaspar P
; Al-Bayati FA
; Andrew PW
; Neves AR
; Yesilkaya H
Infect Immun
2014[Dec]; 82
(12
): 5099-109
PMID25245810
show ga
Streptococcus pneumoniae is a fermentative microorganism and causes serious
diseases in humans, including otitis media, bacteremia, meningitis, and
pneumonia. However, the mechanisms enabling pneumococcal survival in the host and
causing disease in different tissues are incompletely understood. The available
evidence indicates a strong link between the central metabolism and pneumococcal
virulence. To further our knowledge on pneumococcal virulence, we investigated
the role of lactate dehydrogenase (LDH), which converts pyruvate to lactate and
is an essential enzyme for redox balance, in the pneumococcal central metabolism
and virulence using an isogenic ldh mutant. Loss of LDH led to a dramatic
reduction of the growth rate, pinpointing the key role of this enzyme in
fermentative metabolism. The pattern of end products was altered, and lactate
production was totally blocked. The fermentation profile was confirmed by in vivo
nuclear magnetic resonance (NMR) measurements of glucose metabolism in nongrowing
cell suspensions of the ldh mutant. In this strain, a bottleneck in the
fermentative steps is evident from the accumulation of pyruvate, revealing LDH as
the most efficient enzyme in pyruvate conversion. An increase in ethanol
production was also observed, indicating that in the absence of LDH the redox
balance is maintained through alcohol dehydrogenase activity. We also found that
the absence of LDH renders the pneumococci avirulent after intravenous infection
and leads to a significant reduction in virulence in a model of pneumonia that
develops after intranasal infection, likely due to a decrease in energy
generation and virulence gene expression.
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