Lactate dehydrogenase is the key enzyme for pneumococcal pyruvate metabolism and pneumococcal survival in blood.

Abstract:

: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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Gaspar P,Al-Bayati FA,Andrew PW,Neves AR,Yesilkaya H

doi

10.1128/IAI.02005-14

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

5099-109

issue

12

eissn

0019-9567

issn

1098-5522

pii

IAI.02005-14

journal_volume

82

pub_type

杂志文章
  • Immunogenic proteins of Trichomonas vaginalis as demonstrated by the immunoblot technique.

    abstract::Fifteen clinical isolates of Trichomonas vaginalis were evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with transfer to nitrocellulose and by immunoblots probed with human sera. All T. vaginalis isolates showed similar banding patterns by Coomassie brilliant blue and silver staining of the elec...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.51.1.250-253.1986

    authors: Garber GE,Proctor EM,Bowie WR

    更新日期:1986-01-01 00:00:00

  • An msbB homologue carried in plasmid pO157 encodes an acyltransferase involved in lipid A biosynthesis in Escherichia coli O157:H7.

    abstract::Escherichia coli O157:H7 carries a chromosomal msbB1 and a plasmid-encoded msbB2 gene. We characterized msbB2 function as a homologue of msbB1 by examination of wild-type organisms and mutant strains that lacked functional msbB1, msbB2, and both msbB1 and msbB2. The msbB double-mutant strain generated pentaacyl lipid ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.72.2.1174-1180.2004

    authors: Kim SH,Jia W,Bishop RE,Gyles C

    更新日期:2004-02-01 00:00:00

  • CyaC-mediated activation is important not only for toxic but also for protective activities of Bordetella pertussis adenylate cyclase-hemolysin.

    abstract::Bordetella pertussis adenylate cyclase-hemolysin (AC-Hly), encoded by the cyaA gene, belongs to the RTX family of toxins with extensive glycine-rich repeats in the carboxy-terminal portion. AC-Hly possesses both adenylate cyclase toxic and hemolytic activities that depend on a posttranslational modification mediated b...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.61.9.3583-3589.1993

    authors: Betsou F,Sebo P,Guiso N

    更新日期:1993-09-01 00:00:00

  • Influenza virus population dynamics in the respiratory tract of experimentally infected mice.

    abstract::Virus population dynamics in the lungs, trachea, and nasopharynx of Swiss-ICR mice were studied after respiratory challenge with mouse-adapted preparations of strain A2/Aichi/2/68 influenza virus. Markedly higher doses of virus were required to produce infection with nasopharyngeal challenge than with bronchoalveolar ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.13.2.438-447.1976

    authors: Larson EW,Dominik JW,Rowberg AH,Higbee GA

    更新日期:1976-02-01 00:00:00

  • Clostridium difficile toxins A and B directly stimulate human mast cells.

    abstract::Clostridium difficile toxins A and B (TcdA and TcdB) are the causative agents of antibiotic-associated pseudomembranous colitis. Mucosal mast cells play a crucial role in the inflammatory processes underlying this disease. We studied the direct effects of TcdA and TcdB on the human mast cell line HMC-1 with respect to...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00195-07

    authors: Meyer GK,Neetz A,Brandes G,Tsikas D,Butterfield JH,Just I,Gerhard R

    更新日期:2007-08-01 00:00:00

  • Interleukin-25 (IL-25) promotes efficient protective immunity against Trichinella spiralis infection by enhancing the antigen-specific IL-9 response.

    abstract::Mammalian hosts often develop distinct immune response against the diverse parasitic helminths that have evolved for immune evasion. Interleukin-25 (IL-25), an IL-17 cytokine family member, plays a key role in initiating the protective immunity against several parasitic helminths; however, the involvement and underlyi...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00646-13

    authors: Angkasekwinai P,Srimanote P,Wang YH,Pootong A,Sakolvaree Y,Pattanapanyasat K,Chaicumpa W,Chaiyaroj S,Dong C

    更新日期:2013-10-01 00:00:00

  • Cooperation, quorum sensing, and evolution of virulence in Staphylococcus aureus.

    abstract::The virulence and fitness in vivo of the major human pathogen Staphylococcus aureus are associated with a cell-to-cell signaling mechanism known as quorum sensing (QS). QS coordinates the production of virulence factors via the production and sensing of autoinducing peptide (AIP) signal molecules by the agr locus. Her...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.01216-13

    authors: Pollitt EJ,West SA,Crusz SA,Burton-Chellew MN,Diggle SP

    更新日期:2014-03-01 00:00:00

  • Production and partial characterization of a Vibrio fluvialis cytotoxin.

    abstract::Conditions are described for the production of an extracellular cytotoxin or CHO cell-killing factor by Vibrio fluvialis, a recently recognized enteric pathogen. The cell-killing factor was ammonium sulfate precipitable, heat labile, and inactivated by proteases, and had an isoelectric point (estimated by sucrose dens...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.46.3.773-777.1984

    authors: Wall VW,Kreger AS,Richardson SH

    更新日期:1984-12-01 00:00:00

  • Interleukin-12 modulates the protective immune response in SCID mice infected with Histoplasma capsulatum.

    abstract::Infection with Histoplasma capsulatum results in a subclinical infection in immunocompetent hosts due to an effective cellular immune response. By contrast, immunodeficient individuals can have a severe disseminated and potentially fatal disease. In a previous study, it was demonstrated that normal mice infected intra...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.65.3.936-942.1997

    authors: Zhou P,Sieve MC,Tewari RP,Seder RA

    更新日期:1997-03-01 00:00:00

  • Role of protein A in the serum-soft agar technique.

    abstract::Formation of compact colonies of Staphylococcus aureus in serum-soft agar is mainly a result of a reaction between protein A and the Fc-part of immunoglobulin G and not a clumping factor-fibrinogen reaction. ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.6.4.583-586.1972

    authors: Forsum U,Forsgren A,Hjelm E

    更新日期:1972-10-01 00:00:00

  • Correlation of DNA, RNA, and protein content by flow cytometry in normal and Coxiella burnetii-infected L929 cells.

    abstract::L929 cell populations persistently infected for more than 600 days exhibited cell cycle distributions and generation times similar to those of uninfected cells. The RNA and protein contents of these long-term-infected cells, as determined by flow cytometry and correlated with the cell cycle, were likewise approximatel...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.55.7.1731-1733.1987

    authors: Baca OG,Crissman HA

    更新日期:1987-07-01 00:00:00

  • Th1-directing adjuvants increase the immunogenicity of oligosaccharide-protein conjugate vaccines related to Streptococcus pneumoniae type 3.

    abstract::Oligosaccharide (OS)-protein conjugates are promising candidate vaccines against encapsulated bacteria, such as Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae. Although the effects of several variables such as OS chain length and protein carrier have been studied, little is known about th...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.71.12.6915-6920.2003

    authors: Lefeber DJ,Benaissa-Trouw B,Vliegenthart JF,Kamerling JP,Jansen WT,Kraaijeveld K,Snippe H

    更新日期:2003-12-01 00:00:00

  • Vacuole acidification is not required for survival of Salmonella enterica serovar typhimurium within cultured macrophages and epithelial cells.

    abstract::Phagosome acidification is an important component of the microbicidal response by infected eukaryotic cells. Thus, intracellular pathogens that reside within phagosomes must either block phagosome acidification or be able to survive at low pH. In this work, we studied the effect of phagosomal acidification on the surv...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.68.9.5401-5404.2000

    authors: Steele-Mortimer O,St-Louis M,Olivier M,Finlay BB

    更新日期:2000-09-01 00:00:00

  • Role of capsule and suilysin in mucosal infection of complement-deficient mice with Streptococcus suis.

    abstract::Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3(-/-) mice demonst...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00080-14

    authors: Seitz M,Beineke A,Singpiel A,Willenborg J,Dutow P,Goethe R,Valentin-Weigand P,Klos A,Baums CG

    更新日期:2014-06-01 00:00:00

  • Salmonella enterica serovar Pullorum persists in splenic macrophages and in the reproductive tract during persistent, disease-free carriage in chickens.

    abstract::Salmonella enterica serovar Pullorum is worldwide a poultry pathogen of considerable economic importance, particularly in those countries with a developing poultry industry. In addition to the characteristic high mortality rates among young chicks, one of the features of Salmonella serovar Pullorum infection is that i...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.69.12.7873-7879.2001

    authors: Wigley P,Berchieri A Jr,Page KL,Smith AL,Barrow PA

    更新日期:2001-12-01 00:00:00

  • Immunogenicity in a mouse model of a conjugate vaccine made with a synthetic single repeating unit of type 14 pneumococcal polysaccharide coupled to CRM197.

    abstract::Oligosaccharides (OSs) related to the pneumococcal type 14 capsular polysaccharide (Pn14PS) were studied for their ability to inhibit the binding between anti-PS14 antisera and native PS14. A synthetic tetrasaccharide corresponding to the repeating unit of the Pn14PS, a hexasaccharide mimic, and an octasaccharide frag...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.70.9.5107-5114.2002

    authors: Mawas F,Niggemann J,Jones C,Corbel MJ,Kamerling JP,Vliegenthart JF

    更新日期:2002-09-01 00:00:00

  • Host defenses in murine malaria: analysis of plasmodial infection-caused defects in macrophage microbicidal capacities.

    abstract::Macrophage-dependent killing of facultative intracellular bacteria was markedly impaired by overt erythrocytic Plasmodium yoelii or Plasmodium berghei infection of mice. P. yoelii infection was capable of ablating not only the macrophage microbicidal capacity of "normal" animals but also the bactericidal capacities of...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.31.1.396-407.1981

    authors: Murphy JR

    更新日期:1981-01-01 00:00:00

  • Failure to detect cell-mediated cytotoxicity against Chlamydia trachomatis-infected cells.

    abstract::Mice were infected with Chlamydia trachomatis (L2/434) and at various intervals after infection their lymphoid cells were tested directly for cytotoxic activity against Chlamydia-infected L929 cells. In a modified cell-mediated lympholysis assay, splenic, lymph node, and peritoneal exudate cells did not significantly ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.39.3.1271-1274.1983

    authors: Pavia CS,Schachter J

    更新日期:1983-03-01 00:00:00

  • Systemic and mucosal immune responses after intranasal administration of recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing glutathione S-transferase from Schistosoma haematobium.

    abstract::A major goal of current vaccine development is the induction of strong immune responses against protective antigens delivered by mucosal routes. One of the most promising approaches in that respect relies on the use of live recombinant vaccine carriers. In this study, Mycobacterium bovis BCG was engineered to produce ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.66.12.5669-5676.1998

    authors: Kremer L,Dupré L,Riveau G,Capron A,Locht C

    更新日期:1998-12-01 00:00:00

  • Transposon Sequencing of Brucella abortus Uncovers Essential Genes for Growth In Vitro and Inside Macrophages.

    abstract::Brucella abortus is a class III zoonotic bacterial pathogen able to survive and replicate inside host cells, including macrophages. Here we report a multidimensional transposon sequencing analysis to identify genes essential for Brucella abortus growth in rich medium and replication in RAW 264.7 macrophages. The const...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.00312-18

    authors: Sternon JF,Godessart P,Gonçalves de Freitas R,Van der Henst M,Poncin K,Francis N,Willemart K,Christen M,Christen B,Letesson JJ,De Bolle X

    更新日期:2018-07-23 00:00:00

  • Virulence criteria for Brucella abortus strains as determined by interferon regulatory factor 1-deficient mice.

    abstract::Interferon regulatory factor 1-deficient (IRF-1(-/-)) mice infected with virulent Brucella abortus 2308 at 5 x 10(5) CFU developed acute hepatitis similar to many natural hosts but, unlike natural hosts, IRF-1(-/-) mice were unable to resolve infection and died. In contrast, IRF-1(-/-) mice survived when infected at 5...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.70.12.7004-7012.2002

    authors: Ko J,Gendron-Fitzpatrick A,Ficht TA,Splitter GA

    更新日期:2002-12-01 00:00:00

  • New type of exfoliatin obtained from staphylococcal strains, belonging to phage groups other than group II, isolated from patients with impetigo and Ritter's disease.

    abstract::Four strains of Staphylococcus aureus of a phage type other than the second group, isolated from patients with impetigo and Ritter's disease, were found to produce an exotoxin similar to those reported by Melish et al. (1972), Kapral and Miller (1971), and Arbuthnott et al. (1973). This toxin could elicit a general ex...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.10.4.851-861.1974

    authors: Kondo I,Sakurai S,Sarai Y

    更新日期:1974-10-01 00:00:00

  • Identification and functional characterization of chicken toll-like receptor 5 reveals a fundamental role in the biology of infection with Salmonella enterica serovar typhimurium.

    abstract::Toll-like receptors (TLRs) are a major component of the pattern recognition receptor repertoire that detect invading microorganisms and direct the vertebrate immune system to eliminate infection. In chickens, the differential biology of Salmonella serovars (systemic versus gut-restricted localization) correlates with ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.73.4.2344-2350.2005

    authors: Iqbal M,Philbin VJ,Withanage GS,Wigley P,Beal RK,Goodchild MJ,Barrow P,McConnell I,Maskell DJ,Young J,Bumstead N,Boyd Y,Smith AL

    更新日期:2005-04-01 00:00:00

  • Roles of peripheral leukocytes and tissue macrophages in antibacterial resistance induced by free or liposome-encapsulated muramyl tripeptide phosphatidylethanolamide.

    abstract::Administration of free muramyl tripeptide phosphatidylethanolamide (MTPPE) or liposome-encapsulated MTPPE (LE-MTPPE) in a twofold-lower dose at 24 h before bacterial inoculation resulted in clearance of intravenously inoculated Klebsiella pneumoniae by tissue macrophages, whereas in control mice, bacteria were not eff...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.60.11.4891-4897.1992

    authors: Melissen PM,van Vianen W,Bakker-Woudenberg IA

    更新日期:1992-11-01 00:00:00

  • Purification and analysis with monoclonal antibodies of P2, the major outer membrane protein of nontypable Haemophilus influenzae.

    abstract::The protein P2 comprises a large proportion of the outer membrane of nontypable Haemophilus influenzae and functions as a porin. In view of the importance of the protein as a surface antigen, the present study was designed to purify and analyze P2 with particular emphasis on detection of antigenic determinants express...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.56.5.1084-1089.1988

    authors: Murphy TF,Bartos LC

    更新日期:1988-05-01 00:00:00

  • Phosphoinositide 3 kinase mediates Toll-like receptor 4-induced activation of NF-kappa B in endothelial cells.

    abstract::Many of the proinflammatory effects of gram-negative bacteria are elicited by the interaction of bacterial lipopolysaccharide (LPS) with Toll-like receptor 4 (TLR4) expressed on host cells. TLR4 signaling leads to activation of NF-kappa B and transcription of many genes involved in the inflammatory response. In this s...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.71.8.4414-4420.2003

    authors: Li X,Tupper JC,Bannerman DD,Winn RK,Rhodes CJ,Harlan JM

    更新日期:2003-08-01 00:00:00

  • Recombinant human bactericidal/permeability-increasing protein (rBPI23) is a universal lipopolysaccharide-binding ligand.

    abstract::A recombinant 23-kDa protein (rBPI23) derived from human bactericidal/permeability-increasing protein (BPI) possesses potent endotoxin-neutralizing abilities in vitro and in vivo. Binding of rBPI23 to those endotoxins (lipopolysaccharides [LPSs]) encountered clinically would be a prerequisite for efficacy in decreasin...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.62.8.3564-3567.1994

    authors: Appelmelk BJ,An YQ,Thijs BG,MacLaren DM,de Graaff J

    更新日期:1994-08-01 00:00:00

  • Macrophage activation during experimental murine brucellosis: a basis for chronic infection.

    abstract::Evidence is presented that the chronicity of infection in CBA mice after injection of Brucella abortus 19 is related to a number of factors: (i) the relative resistance of B. abortus to macrophage killing, which allowed some bacteria to survive the peak of macrophage activity occurring at 14 days; (ii) the decline in ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.23.2.197-205.1979

    authors: Cheers C,Pagram F

    更新日期:1979-02-01 00:00:00

  • Intravaginal and intranasal immunizations are equally effective in inducing vaginal antibodies and conferring protection against vaginal candidiasis.

    abstract::Oophorectomized, estrogen-treated rats were immunized by the intravaginal or intranasal route with a mannoprotein extract (MP) or secreted aspartyl proteinases (Sap) of Candida albicans, with or without cholera toxin as a mucosal adjuvant. Both routes of immunization were equally effective in (i) inducing anti-MP and ...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/iai.70.5.2725-2729.2002

    authors: De Bernardis F,Boccanera M,Adriani D,Girolamo A,Cassone A

    更新日期:2002-05-01 00:00:00

  • Inability of pyrogenic, purified Bordetella pertussis lipid A to induce interleukin-1 release by human monocytes.

    abstract::Free lipid A of Bordetella pertussis, Neisseria meningitidis, and Escherichia coli lipopolysaccharide (LPS) was prepared by hydrolysis in acetate buffer (pH 4.5); in addition, lipid A from B. pertussis and E. coli was prepared by hydrolysis in mineral acid (HCl). The precipitates obtained were purified by extraction m...

    journal_title:Infection and immunity

    pub_type: 杂志文章

    doi:10.1128/IAI.54.2.465-471.1986

    authors: Caroff M,Cavaillon JM,Fitting C,Haeffner-Cavaillon N

    更新日期:1986-11-01 00:00:00