Characterization of Central Carbon Metabolism of Streptococcus pneumoniae by Isotopologue Profiling

Härtel, Tobias; Eylert, Eva; Schulz, Christian; Petruschka, Lothar; Gierok, Philipp; Grubmüller, Stephanie; Lalk, Michael; Eisenreich, Wolfgang; Hammerschmidt, Sven

doi:10.1074/jbc.m111.304311

Cited by 70 publications

(108 citation statements)

References 68 publications

(120 reference statements)

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…1A). Pneumococci have been shown to be auxotrophic for cysteine when grown in chemically defined medium (CDM) (11). To determine if pneumococci are able to use GSH as a source of cysteine, and if this is dependent on GSH uptake via GshT as is the case in S. mutans, we conducted growth experiments in CDM.…”

Section: Identification Of the S Pneumoniae Glutathione Transportermentioning

confidence: 99%

Streptococcus pneumoniae Uses Glutathione To Defend against Oxidative Stress and Metal Ion Toxicity

2012

View full text Add to dashboard Cite

The thiol-containing tripeptide glutathione is an important cellular constituent of many eukaryotic and prokaryotic cells. In addition to its disulfide reductase activity, glutathione is known to protect cells from many forms of physiological stress. This report represents the first investigation into the role of glutathione in the Gram-positive pathogen Streptococcus pneumoniae. We demonstrate that pneumococci import extracellular glutathione using the ABC transporter substrate binding protein GshT. Mutation of gshT and the gene encoding glutathione reductase (gor) increases pneumococcal sensitivity to the superoxide generating compound paraquat, illustrating the importance of glutathione utilization in pneumococcal oxidative stress resistance. In addition, the gshT and gor mutant strains are hypersensitive to challenge with the divalent metal ions copper, cadmium, and zinc. The importance of glutathione utilization in pneumococcal colonization and invasion of the host is demonstrated by the attenuated phenotype of the gshT mutant strain in a mouse model of infection.

show abstract

Section: Identification Of the S Pneumoniae Glutathione Transportermentioning

confidence: 99%

Streptococcus pneumoniae Uses Glutathione To Defend against Oxidative Stress and Metal Ion Toxicity

2012

View full text Add to dashboard Cite

show abstract

“…13 C enrichments and isotopologue profiles of protein-bound amino acids were used to identify nutrient usage and metabolic pathways, even under complex environmental conditions. This technique was used to investigate the carbon metabolism of Listeria monocytogenes, Salmonella enterica, and Streptococcus pneumoniae (20)(21)(22)(23). There is growing evidence that central metabolic pathways are linked to virulence in particular pathogens.…”

mentioning

confidence: 99%

Growth Media Simulating Ileal and Colonic Environments Affect the Intracellular Proteome and Carbon Fluxes of Enterohemorrhagic Escherichia coli O157:H7 Strain EDL933

Polzin

Huber

Eylert

et al. 2013

Appl Environ Microbiol

Self Cite

View full text Add to dashboard Cite

In this study, the intracellular proteome of Escherichia coli O157:H7 strain EDL933 was analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) spectrometry after growth in simulated ileal environment media (SIEM) and simulated colonic environment media (SCEM) under aerobic and microaerobic conditions. Differentially expressed intracellular proteins were identified and allocated to functional protein groups. Moreover, metabolic fluxes were analyzed by isotopologue profiling with [U-13 C 6 ]glucose as a tracer. The results of this study show that EDL933 responds with differential expression of a complex network of proteins and metabolic pathways, reflecting the high metabolic adaptability of the strain. Growth in SIEM and SCEM is obviously facilitated by the upregulation of nucleotide biosynthesis pathway proteins and could be impaired by exposition to 50 M 6-mercaptopurine under aerobic conditions. Notably, various stress and virulence factors, including Shiga toxin, were expressed without having contact with a human host.

show abstract

“…Pneumococci further produce methionine biosynthesis enzymes (D39: Spd_0510 -Spd_0511; TIGR4 Sp_0585 -Sp_0586, MetE and MetF). The lack of methionine in a chemically defined medium affects growth of pneumococci and similar, the lack of the methionine binding lipoprotein MetQ impaired uptake of methionine 32,33 . This defect could be restored by the addition of high concentrations of methionine.…”

Section: Representative Resultsmentioning

confidence: 99%

“…The acquisition and uptake of methionine is of central importance for pneumococci to maintain fitness in their host niche 32,33 . The methionine ABC transporter lipoprotein is encoded in D39 by the spd_0151 gene (TIGR4: sp_0149) and named MetQ 32 .…”

Section: Representative Resultsmentioning

confidence: 99%

Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria

Saleh

Abdullah

Schulz

et al. 2014

JoVE

Self Cite

View full text Add to dashboard Cite

Pneumonia is one of the major health care problems in developing and industrialized countries and is associated with considerable morbidity and mortality. Despite advances in knowledge of this illness, the availability of intensive care units (ICU), and the use of potent antimicrobial agents and effective vaccines, the mortality rates remain high 1 . Streptococcus pneumoniae is the leading pathogen of community-acquired pneumonia (CAP) and one of the most common causes of bacteremia in humans. This pathogen is equipped with an armamentarium of surface-exposed adhesins and virulence factors contributing to pneumonia and invasive pneumococcal disease (IPD). The assessment of the in vivo role of bacterial fitness or virulence factors is of utmost importance to unravel S. pneumoniae pathogenicity mechanisms. Murine models of pneumonia, bacteremia, and meningitis are being used to determine the impact of pneumococcal factors at different stages of the infection. Here we describe a protocol to monitor in real-time pneumococcal dissemination in mice after intranasal or intraperitoneal infections with bioluminescent bacteria. The results show the multiplication and dissemination of pneumococci in the lower respiratory tract and blood, which can be visualized and evaluated using an imaging system and the accompanying analysis software. Video LinkThe video component of this article can be found at

show abstract

Characterization of Central Carbon Metabolism of Streptococcus pneumoniae by Isotopologue Profiling

Cited by 70 publications

References 68 publications

Streptococcus pneumoniae Uses Glutathione To Defend against Oxidative Stress and Metal Ion Toxicity

Streptococcus pneumoniae Uses Glutathione To Defend against Oxidative Stress and Metal Ion Toxicity

Growth Media Simulating Ileal and Colonic Environments Affect the Intracellular Proteome and Carbon Fluxes of Enterohemorrhagic Escherichia coli O157:H7 Strain EDL933

Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria

Contact Info

Product

Resources

About