Biofilms of Escherichia coli O157:H7 were developed on stainless steel chips in trypticase soy broth (TSB), 1/5 dilution of TSB, 0.1% Bacto peptone (BP) and a minimal salts medium (MSM) supplemented with 0.04% of one of the following carbon sources: glucose, glycerol, lactose, mannose, succinic acid, sodium pyruvate or lactic acid. It was found that biofilms developed faster and a higher number of adherent cells (ca. 10(6) CFU/cm2) were recovered when the organisms were grown in the low nutrient media. Regardless of the carbon source, biofilms developed in MSM consisted of shorter bacterial cells and thicker extracellular matrix (ECM), with glucose as the best substrate for stable biofilm formation. Fewer bacteria in initial attachment, non-hydrophobicity of bacterial cells, lack of ECM formation and easy detachment of the biofilm bacteria may contribute to poor biofilm formation in TSB. ECM is probably important for the stability of biofilms; however, at 10 degrees C and under anaerobic conditions, ECM seems to be unnecessary.

BACKGROUND

National reports of a dramatic rise in sepsis incidence are largely based on analyses of administrative databases. It is unclear if these estimates are biased by changes in coding practices over time.

METHODS

We calculated linear trends in the annual incidence of septicemia, sepsis, and severe sepsis at 2 academic hospitals from 2003 to 2012 using 5 different claims methods and compared case identification rates to selected objective clinical markers, including positive blood cultures, vasopressors, and/or lactic acid levels.

RESULTS

The annual incidence of hospitalizations with sepsis claims increased over the decade, ranging from a 54% increase for the method combining septicemia, bacteremia, and fungemia codes (P < .001 for linear trend) to a 706% increase for explicit severe sepsis/septic shock codes (P = .001). In contrast, the incidence of hospitalizations with positive blood cultures decreased by 17% (P = .006), and hospitalizations with positive blood cultures with concurrent vasopressors and/or lactic acidosis remained stable (P = .098). The sensitivity of sepsis claims for capturing hospitalizations with positive blood cultures with concurrent vasopressors and/or lactic acidosis increased (P < .001 for all methods), whereas the proportion of septicemia hospitalizations with positive blood cultures decreased from 50% to 30% (P < .001).

CONCLUSIONS

The incidence of hospitalizations with sepsis codes rose dramatically while hospitalizations with corresponding objective clinical markers remained stable or decreased. Coding for sepsis has become more inclusive, and septicemia diagnoses are increasingly being applied to patients without positive blood cultures. These changes likely explain some of the apparent rise in sepsis incidence and underscore the need for more reliable surveillance methods.

Enolase occurs as a cytoplasmic and a surface-associated protein in bacteria. Enolases of the bacterial pathogens Streptococcus pyogenes, Streptococcus pneumoniae and Staphylococcus aureus, as well as of the commensal lactic acid bacteria, Lactobacillus crispatus and Lactobacillus johnsonii, were purified as His(6)-fusion proteins from recombinant Escherichia coli. The fusion proteins were compared for putative virulence-associated functions, i.e., binding of human plasminogen, enhancement of plasminogen activation by human plasminogen activators, as well as binding to immobilized laminin, fibronectin and collagens. The individual enolases showed varying efficiencies in these functions. In particular, highly and equally effective interactions with plasminogen and laminin were seen with lactobacillar and staphylococcal enolases.

Streptococci are the primary component of the multispecies oral biofilm known as supragingival dental plaque; they grow by fermentation of sugars to organic acids, e.g., lactic acid. Veillonellae, a ubiquitous component of early plaque, are unable to use sugars; they ferment organic acids, such as lactate, to a mixture of shorter-chain-length acids, CO(2), and hydrogen. Certain veillonellae bind to (coaggregate with) streptococci in vitro. We show that, between 4 and 8 hours into plaque development, the dominant strains of Veillonella change in their phenotypic characteristics (coaggregation and antibody reactivity) as well as in their genotypic characteristics (16S RNA gene sequences as well as strain level fingerprint patterns). This succession is coordinated with the development of mixed-species bacterial colonies. Changes in community structure can occur very rapidly in natural biofilm development, and we suggest that this process may influence evolution within this ecosystem.

Lactococcus lactis NZ9000 and its parent MG1363 are the most commonly used lactic acid bacteria for expression and physiological studies. We noted unexpected but significant differences in the growth behaviors of both strains. We sequenced the entire genomes of the original NZ9000 and MG1363 strains using an ultradeep sequencing strategy. The analysis of the L. lactis NZ9000 genome yielded 79 differences, mostly point mutations, with the annotated genome sequence of L. lactis MG1363. Resequencing of the MG1363 strain revealed that 73 out of the 79 differences were due to errors in the published sequence. Comparative transcriptomic studies revealed several differences in the regulation of genes involved in sugar fermentation, which can be explained by two specific mutations in a region of the ptcC promoter with a key role in the regulation of cellobiose and glucose uptake.

Group B streptococcus (GBS) is an important human pathogen. In this study, we sought to identify mechanisms that may protect GBS from host defenses in addition to its capsular polysaccharide. A gene encoding a cell-surface-associated protein (cspA) was characterized from a highly virulent type III GBS isolate, COH1. Its sequence indicated that it is a subtilisin-like extracellular serine protease homologous to streptococcal C5a peptidases and caseinases of lactic acid bacteria. The wild-type strain cleaved the alpha chain of human fibrinogen, whereas a cspA mutant, TOH121, was unable to cleave fibrinogen. We observed aggregated material when COH1 was incubated with fibrinogen but not when the mutant strain was treated similarly. This suggested that the product(s) of fibrinogen cleavage have strong adhesive properties and may be similar to fibrin. The cspA gene was present among representative clinical isolates from all nine capsular serotypes, as revealed by Southern blotting. A cspA(-) mutant was ten times less virulent in a neonatal rat sepsis model of GBS infections, as measured by LD(50) analysis. In addition, the cspA(-) mutant was significantly more sensitive than the wild-type strain to opsonophagocytic killing by human neutrophils in vitro. Taken together, the results suggest that cleavage of fibrinogen by CspA may increase the lethality of GBS infection, potentially by protecting the bacterium from opsonophagocytic killing.

Considerable advances have been made in the genetics and molecular biology of lactic acid bacteria, including Lactococcus, Lactobacillus, Leuconostoc, Pediococcus and Streptococcus spp. These have resulted in the construction of constitutive gene expression cassettes, inducible gene expression systems, and specific protein targeting systems for these bacteria. These developments are important in the food industry where lactic acid bacteria can be exploited as food-grade cell factories.

The aim of the study was to investigate the effect of the size and PEG coating density of Poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) nano- and microparticles on their transport across the nasal mucosa. Particles were made of PLA-PEG copolymers of two different molecular weights (Mw: 37 and 28 kDa) and also PLA of Mw 28 kDa, and prepared using different techniques (simple emulsion (o/w), double emulsion (w/o/w), and nanoprecipitation techniques). The particles were characterized for their size, zeta potential, morphology [Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM)], and PEG coating efficiency. Additionally, the transport of rhodamine 6G-labelled PLA-PEG and PLA particles across the rat nasal mucosa was investigated by Confocal Laser Scanning Microscopy (CLSM). The results showed that the size of PLA-PEG nanoparticles varied between 150 and 300 nm and their zeta potential between -10 and -22 mV depending on both the polymer Mw and the preparation technique. Moreover, the PEG coating efficiency (amount of PEG on the surface with respect to the total amount of PEG in the particles) was high (between 75% and 92%) and affected by the PLA Mw and also by the particles preparation technique. The greatest PEG surface density was achieved for lowest Mw PLA-PEG, using the O/W emulsification technique. The CLSM images of nasal epithelia from rats showed the importance of the PEG coating density and the size on the transmucosal transport of the fluorescent nanoparticles. More specifically, PLA-PEG particles with a high PEG coating density and a small size were more significantly transported than noncoated PLA nanoparticles and also than PLA-PEG nanoparticles with a lower coating density. In conclusion, these results showed the important role that the PEG coating has on the efficacy of PLA-PEG nanoparticles as nasal drug carriers.

Solid tumors have been observed to develop an acidic extracellular environment, which is believed to occur as a result of lactic acid accumulation produced during aerobic and anaerobic glycolysis. Experiments using glycolysis-deficient ras-transfected Chinese hamster lung fibroblasts have been performed to test the hypothesis that lactic acid production within solid tumors is responsible for the development of tumor acidity. The variant cells have defects in glucose transport and in the glycolytic enzyme phosphoglucose isomerase with 1% activity compared to parental cells. Consequently, the in vitro rate of lactic acid production by variant cells was < 4% compared to parental cells. An in vitro correlation between lactic acid production and acidification of exposure medium was observed for parental and variant cells. Implantation of both cell lines into nude mice led to tumors with minimal difference in growth rate. As expected, variant cells died when exposed to hypoxic conditions in culture, and parental tumors were observed to have a larger fraction of cells resistant to radiation due to hypoxia (27%) than variant tumors (2%). Using pH microelectrodes, parental (n = 12) and variant (n = 12) tumors were observed to have extracellular pH (pHe) values of 6.65 +/- 0.07 and 6.78 +/- 0.04 (mean +/- SE, P = 0.13), respectively, whereas normal muscle had a pHe of 7.29 +/- 0.06 (P < 0.0001 for both cell lines). The lactic acid content of variant tumors was found to be similar to that in serum, whereas parental tumors had lactic acid content that was higher than in serum (P < 0.0001). We conclude that there was no correlation between lactic acid content and acidosis for these tumors derived from ras-transfected fibroblasts. These results provide evidence that the production of lactic acid via glycolysis is not the only mechanism responsible for the development of an acidic environment within solid tumors.

The importance of granular (lysosomal) enzymes from neutrophils in producing the tissue damage of acute inflammation has been suggested by much indirect and some direct evidence. This study has investigated the kinetics of release and subsequent fate of granular enzymes from phagocytizing human leukocytes The following observations are made: (a) During phagocytosis, the granular enzyme lysozyme is released from leukocytes into the extracellular medium. (b) Release of lysozyme increases as phagocytic challenge increases, but attains a maximum. (c) Release of lysozyme accompanies phagocytosis and is not a delayed event. (d) The lack of release of a nongranular enzyme, lactic dehydrogenase, indicates that cell damage is not a necessary condition of enzyme release. (e) Like lysozyme, beta-glucuronidase is released from phagocytizing leukocytes. Acid alpha-naphthyl phosphatase and cathepsin also appear to be released, but are not found in appreciable amounts in the extracellular medium, in part because of their lability in solution. These results support the concept that extracellular release of granular enzymes may be a useful secretory function of inflammatory leukocytes which becomes damaging to the host in certain circumstances.

Given that the microbiota of the healthy vagina plays an important role in the maintenance of health, it follows that an understanding of its composition and development may offer insights into the etiology and prevention of disease. In contrast to previous studies, this study exclusively investigated the structure and composition of adolescent vaginal bacterial communities. In this report, the vaginal bacterial communities of 90 menarcheal adolescents, ages 13-18y, were characterized using terminal restriction fragment length polymorphisms (T-RFLP) of 16S rRNA genes. Further characterization involved cluster analysis of the T-RFLP data to identify the number of different kinds of microbial communities found among the adolescents sampled, and phylogenetic analysis of 16S rRNA gene sequences cloned from samples representative of each cluster. We report the identification of four major clusters that accounted for 96.7% of the cohort. In general, these clusters could be divided into those dominated by Lactobacillus spp. and those dominated by a variety of lactic acid producing, anaerobic bacterial types such as Atopobium vaginae and Streptococcus spp. The compositional and structural similarity of the vaginal microbiota of menarcheal adolescents and adults suggests that the vaginal microbiota does not change significantly after the onset of menarche.

OBJECTIVE

The lack of specificity of chemotherapeutic agents to cancer tissue commonly leads to dose-limiting side effects and poor therapeutic results. Drug delivery systems promise to improve the deficiencies of chemotherapeutic treatment by modifying the biodistribution and pharmacokinetics of the drug in vivo. Here, we report the preparation, characterization and in vitro evaluation of a carrier for the chemotherapeutic drug doxorubicin based on acid-capped poly(lactic-co-glycolic acid) nanoparticles.

METHODS

Doxorubicin-loaded nanoparticles were prepared by nanoprecipitation with bovine serum albumin as the stabilizer. Nanoparticles were characterized and their interaction with MDA-MB-231 breast cancer cells was examined with confocal microscopy and a toxicological assay.

RESULTS

Spherical particles with an average diameter of 230 nm, a zeta-potential of -45 mV and a maximum drug loading of 5 wt% were prepared. Doxorubicin was found to be quickly released at endolysosomal pH of 4.0 but was released at a slower rate at pH 7.4. Nanoparticles were found to deliver the drug into cells quickly and in higher quantity than when presented in solution and were found to result in a therapeutic efficacy comparable to the free drug.

CONCLUSIONS

Nanoprecipitation was found to be a promising method for the preparation of nanoparticles with relatively high doxorubicin loading. The pH-dependent release behavior is discussed to possibly be a result of accelerated degradation of the polymer and decreasing ionic interaction between the drug and the polymer at acidic pH. Additional studies are needed to determine why increased nuclear localization of the drug when delivered in the form of nanoparticles did not result in increased therapeutic efficacy in vitro.

CONCLUSIONS

Nanoparticles formulated by nanoprecipitation of acid-ended poly(lactic-co-glycolic acid) were found to be able to control the release of doxorubicin in a pH-dependent manner and to effectively deliver high payloads of the drug in an active form to MDA-MB-231 breast cancer cells.

Everyone who has ever tried to radically change metabolic fluxes knows that it is often harder to determine which enzymes have to be modified than it is to actually implement these changes. In the more traditional genetic engineering approaches 'bottle-necks' are pinpointed using qualitative, intuitive approaches, but the alleviation of suspected 'rate-limiting' steps has not often been successful. Here the authors demonstrate that a model of pyruvate distribution in Lactococcus lactis based on enzyme kinetics in combination with metabolic control analysis clearly indicates the key control points in the flux to acetoin and diacetyl, important flavour compounds. The model presented here (available at http://jjj.biochem.sun.ac.za/wcfs.html) showed that the enzymes with the greatest effect on this flux resided outside the acetolactate synthase branch itself. Experiments confirmed the predictions of the model, i.e. knocking out lactate dehydrogenase and overexpressing NADH oxidase increased the flux through the acetolactate synthase branch from 0 to 75% of measured product formation rates.

Lactacin F is a nonlantibiotic, heat-stable, peptide bacteriocin produced by Lactobacillus johnsonii VPI11088. Molecular analysis of the lactacin F DNA region characterized a small operon that codes for three open reading frames, designated lafA, lafX, and ORFZ. The peptide encoded by lafA, the lactacin F structural gene, was compared with various peptide bacteriocins from lactic acid bacteria, and similarities were identified in the amino and carboxy termini of the propeptides. Site-directed mutagenesis of the LafA precursor at the two glycine residues in positions -1 and -2 defined an essential motif for processing of mature lactacin F. The involvement of the peptides encoded by lafX and ORFZ in bacteriocin expression was investigated by subcloning various fragments from the lactacin F region into the shuttle vector pGKV210. In addition to lafA, expression of lafX is essential to lactacin F activity. The lactacin F operon resembles the genetic organization of lactococcin M. Although no function has been assigned to ORFZ by genetic analysis, both peptide Z and the lactococcin M immunity protein are predicted to be integral membrane proteins with four putative transmembrane segments. Lactacin F activity, defined by bactericidal action on Lactobacillus delbrueckii, is dependent on the expression of two genes, lafA and lafX.

Yeast Saccharomyces cerevisiae is an important industrial host for production of enzymes, pharmaceutical and nutraceutical ingredients and recently also commodity chemicals and biofuels. Here, we review the advances in modeling and synthetic biology tools and how these tools can speed up the development of yeast cell factories. We also present an overview of metabolic engineering strategies for developing yeast strains for production of polymer monomers: lactic, succinic, and cis,cis-muconic acids. S. cerevisiae has already firmly established itself as a cell factory in industrial biotechnology and the advances in yeast strain engineering will stimulate development of novel yeast-based processes for chemicals production.

In this study, we describe composite scaffolds composed of synthetic and natural materials with physicochemical properties suitable for tissue engineering applications. Fibrous scaffolds were co-electrospun from a blend of a synthetic biodegradable polymer (poly(lactic-co-glycolic acid), PLGA, 10% solution) and two natural proteins, gelatin (denatured collagen, 8% solution) and alpha-elastin (20% solution) at ratios of 3:1:2 and 2:2:2 (v/v/v). The resulting PLGA-gelatin-elastin (PGE) fibers were homogeneous in appearance with an average diameter of 380 +/- 80 nm, which was considerably smaller than fibers made under identical conditions from the starting materials (PLGA, 780 +/- 200 nm; gelatin, 447 +/- 123 nm; elastin, 1060 +/- 170 nm). Upon hydration, PGE fibers swelled to an average fiber diameter of 963 +/- 132 nm, but did not disintegrate. Importantly, PGE scaffolds were stable in an aqueous environment without crosslinking and were more elastic than those made of pure elastin fibers. To investigate the cytocompatibility of PGE, we cultured H9c2 rat cardiac myoblasts and rat bone marrow stromal cells (BMSCs) on fibrous PGE scaffolds. We found that myoblasts grew equally as well or slightly better on the scaffolds than on tissue-culture plastic. Microscopic evaluation confirmed that myoblasts reached confluence on the scaffold surfaces while simultaneously growing into the scaffolds. Histological characterization of the PGE constructs indicated that BMSCs penetrated into the center of scaffolds and began proliferating shortly after seeding. Our results suggest that fibrous scaffolds made of PGE and similar biomimetic blends of natural and synthetic polymers may be useful for engineering soft tissues, such as heart, lung, and blood vessels.

Lactic acid bacteria (LAB) have been used for centuries in the fermentation of a variety of dairy products. The preservative ability of LAB in foods is attributed to the production of anti-microbial metabolites including organic acids and bacteriocins. Bacteriocins generally exert their anti-microbial action by interfering with the cell wall or the membrane of target organisms, either by inhibiting cell wall biosynthesis or causing pore formation, subsequently resulting in death. The incorporation of bacteriocins as a biopreservative ingredient into model food systems has been studied extensively and has been shown to be effective in the control of pathogenic and spoilage microorganisms. However, a more practical and economic option of incorporating bacteriocins into foods can be the direct addition of bacteriocin-producing cultures into food. This paper presents an overview of the potential for using bacteriocin-producing LAB in foods for the improvement of the safety and quality of the final product. It describes the different genera of LAB with potential as biopreservatives, and presents an up-to-date classification system for the bacteriocins they produce. While the problems associated with the use of some bacteriocin-producing cultures in certain foods are elucidated, so also are the situations in which incorporation of the bacteriocin-producer into model food systems have been shown to be very effective.

Lactic acid fermentation represents the easiest and the most suitable way for increasing the daily consumption of fresh-like vegetables and fruits. Literature data are accumulating, and this review aims at describing the main features of the lactic acid bacteria to be used for fermentation. Lactic acid bacteria are a small part of the autochthonous microbiota of vegetables and fruits. The diversity of the microbiota markedly depends on the intrinsic and extrinsic parameters of the plant matrix. Notwithstanding the reliable value of the spontaneous fermentation to stabilize and preserve raw vegetables and fruits, a number of factors are in favour of using selected starters. Two main options may be pursued for the controlled lactic acid fermentation of vegetables and fruits: the use of commercial/allochthonous and the use of autochthonous starters. Several evidences were described in favour of the use of selected autochthonous starters, which are tailored for the specific plant matrix. Pro-technological, sensory and nutritional criteria for selecting starters were reported as well as several functional properties, which were recently ascribed to autochthonous lactic acid bacteria. The main features of the protocols used for the manufacture of traditional, emerging and innovative fermented vegetables and fruits were reviewed. Tailored lactic acid bacteria starters completely exploit the potential of vegetables and fruits, which enhances the hygiene, sensory, nutritional and shelf life properties.

In isolated, blood perfused, supramaximally stimulated, isotonically working gastrocnemii of dogs lactic acid (LA) output and O2-consumption (V O2) were measured according to the Fick principle. Simultaneously concentration of muscle tissue was determined at rest and at different times during exercise. In one series of experiments metabolic alkalosis was induced by infusions of THAM of Na bicarbonate. As a result arterial pH increased to about 7.5 and standard [HCO3-1] to 31-35 mmol per 1. In another group of experiments metabolic acidosis was induced by HCl infusions. In these experiments pH decreased to 7.0-7.1 and standard [HO301] to 8-11 mmol per 1. During the first 3-4 min after the onset of exercise LA concentration of muscle tissue rose to 18-19 mumol per g wet weight in both series of experiments. During acidosis the highest average values for LA release from the muscle were about 1.1 mumoles per g per minute. During alkalosis LA permeation rate was nearly three times as high. As a consequence of increased rate of permeation, LA concentration of muscle tissue decreased more rapidly in alkalosis than in acidosis. In both series of experiments work per time and VO2 were practically equal during the first 5-6 min of exercise. Thereafter work per time and VO2 decreased more rapidly in acidosis than in alkalosis, a result which probably is due to higher LA concentration in muscle at this time in acidosis. It is concluded that LA permeation rate across muscle cell membrane is increased by high extracellular HCO3- concentration in combination with low H+ activity and vice versa.

Colorectal cancer is one of the most important causes of cancer morbidity and mortality in western countries [1]. A myriad of healthful effects have been attributed to the probiotic lactic acid bacteria; perhaps the most controversial remains that of anticancer activity. There is no direct experimental evidence for cancer suppression in humans as a result of consumption of lactic cultures in fermented or unfermented dairy products. However, there is a wealth of indirect evidence, based largely on laboratory studies, in the literature and this will be summarised in the present paper.

OBJECTIVE

The main reason for restoration failure is secondary caries caused by biofilm acids. Replacing the failed restorations accounts for 50-70% of all operative work. The objectives of this study were to incorporate a new quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) and nanoparticles of silver (NAg) into a primer and an adhesive, and to investigate their effects on antibacterial and dentin bonding properties.

METHODS

Scotchbond Multi-Purpose (SBMP) served as control. DMADDM was synthesized and incorporated with NAg into primer/adhesive. A dental plaque microcosm biofilm model with human saliva was used to investigate metabolic activity, colony-forming units (CFU), and lactic acid. Dentin shear bond strengths were measured.

RESULTS

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the new DMADDM were orders of magnitude lower than those of a previous quaternary ammonium dimethacrylate (QADM). Uncured primer with DMADDM had much larger inhibition zones than QADM (p<0.05). Cured primer/adhesive with DMADDM-NAg greatly reduced biofilm metabolic activity (p<0.05). Combining DMADDM with NAg in primer/adhesive resulted in less CFU than DMADDM alone (p<0.05). Lactic acid production by biofilms was reduced by 20-fold via DMADDM-NAg, compared to control. Incorporation of DMADDM and NAg into primer/adhesive did not adversely affect dentin bond strength.

CONCLUSIONS

A new antibacterial monomer DMADDM was synthesized and incorporated into primer/adhesive for the first time. The bonding agents are promising to combat residual bacteria in tooth cavity and invading bacteria at tooth-restoration margins to inhibit caries. DMADDM and NAg are promising for use into a wide range of dental adhesive systems and restoratives.

Bile salt hydrolysis is an important metabolic reaction in the bile salt metabolism of mammals. This reaction has a facilitating effect for bile salt excretion but can also be involved in various illnesses. In recent years interest has increased to use bile salt hydrolysis to influence the cholesterol metabolism of humans and farm animals. To understand the distribution and range of bile salt hydrolase activity in lactic acid bacteria, we screened more than 300 strains of the genera Bifidobacterium and Lactobacillus and the species Lactococcus lactis, Leuconostoc mesenteroides, and Streptococcus thermophilus. Results obtained for 273 strains showed that bile salt hydrolase activity is common in Bifidobacterium and Lactobacillus but absent in L. lactis, Leu. mesenteroides, and S. thermophilus. Nearly all bifidobacteria species and strains have bile salt hydrolase activity, whereas this activity can only be found in selected species of lactobacilli. A strong correlation can be observed between the habitat of a genus or species and the presence of bile salt hydrolase activity. Most often bile salt hydrolase activity is found in strains that have been isolated from the intestines or from feces from mammals--an environment rich in conjugated and unconjugated bile acids. Strains and species from other habitats like milk or vegetables--environments from which bile salts are absent--do normally not have bile salt hydrolase activity. In two independent assays, we established that bile salt hydrolase activity in bifidobacteria is, in general, much higher than in lactobacilli.

Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism.