scholarly journals The ClpCP Complex Modulates Respiratory Metabolism inStaphylococcus aureusand Is Regulated in a SrrAB-Dependent Manner

2019 ◽  
Vol 201 (15) ◽  
Author(s):  
Ameya A. Mashruwala ◽  
Brian J. Eilers ◽  
Amanda L. Fuchs ◽  
Javiera Norambuena ◽  
Carly A. Earle ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Energy Metabolism ◽  
Energy Homeostasis ◽  
Protein Complexes ◽  
Present Report ◽  
Bacterial Pathogen ◽  
Dependent Manner ◽  
Content Type ◽  
Fermentative Growth ◽  
Increased Sensitivity

ABSTRACTThestaphylococcalrespiratoryregulator (SrrAB) modulates energy metabolism inStaphylococcus aureus. Studies have suggested that regulated protein catabolism facilitates energy homeostasis. Regulated proteolysis inS. aureusis achieved through protein complexes composed of a peptidase (ClpQ or ClpP) in association with an AAA+family ATPase (typically, ClpC or ClpX). In the present report, we tested the hypothesis that SrrAB regulates a Clp complex to facilitate energy homeostasis inS. aureus. Strains deficient in one or more Clp complexes were attenuated for growth in the presence of puromycin, which causes enrichment of misfolded proteins. A ΔsrrABstrain had increased sensitivity to puromycin. Epistasis experiments suggested that the puromycin sensitivity phenotype of the ΔsrrABstrain was a result of decreased ClpC activity. Consistent with this, transcriptional activity ofclpCwas decreased in the ΔsrrABmutant, and overexpression ofclpCsuppressed the puromycin sensitivity of the ΔsrrABstrain. We also found that ClpC positively influenced respiration and that it did so upon association with ClpP. In contrast, ClpC limited fermentative growth, while ClpP was required for optimal fermentative growth. Metabolomics studies demonstrated that intracellular metabolic profiles of the ΔclpCand ΔsrrABmutants were distinct from those of the wild-type strain, supporting the notion that both ClpC and SrrAB affect central metabolism. We propose a model wherein SrrAB regulates energy homeostasis, in part, via modulation of regulated proteolysis.IMPORTANCEOxygen is used as a substrate to derive energy by the bacterial pathogenStaphylococcus aureusduring infection; however,S. aureuscan also grow fermentatively in the absence of oxygen. To successfully cause infection,S. aureusmust tailor its metabolism to take advantage of respiratory activity. Different proteins are required for growth in the presence or absence of oxygen; therefore, when cells transition between these conditions, several proteins would be expected to become unnecessary. In this report, we show that regulated proteolysis is used to modulate energy metabolism inS. aureus. We report that the ClpCP protein complex is involved in specifically modulating aerobic respiratory growth but is dispensable for fermentative growth.

scholarly journals The Phosphoenolpyruvate:Sugar Phosphotransferase System Is Involved in Sensitivity to the Glucosylated Bacteriocin Sublancin

2015 ◽  
Vol 59 (11) ◽  
pp. 6844-6854 ◽  
Author(s):  
C. V. Garcia De Gonzalo ◽  
E. L. Denham ◽  
R. A. T. Mars ◽  
J. Stülke ◽  
W. A. van der Donk ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Mode Of Action ◽  
Phosphotransferase System ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Distinct Mechanism ◽  
Genomic Studies ◽  
Increased Sensitivity ◽  
Bacterial Sensitivity

ABSTRACTThe mode of action of a group of glycosylated antimicrobial peptides known as glycocins remains to be elucidated. In the current study of one glycocin, sublancin, we identified the phosphoenolpyruvate:sugar phosphotransferase system (PTS) ofBacillusspecies as a key player in bacterial sensitivity. Sublancin kills several Gram-positive bacteria, such asBacillusspecies andStaphylococcus aureus, including methicillin-resistantS. aureus(MRSA). Unlike other classes of bacteriocins for which the PTS is involved in their mechanism of action, we show that the addition of PTS-requiring sugars leads to increased resistance rather than increased sensitivity, suggesting that sublancin has a distinct mechanism of action. Collectively, our present mutagenesis and genomic studies demonstrate that the histidine-containing phosphocarrier protein (HPr) and domain A of enzyme II (PtsG) in particular are critical determinants for bacterial sensitivity to sublancin.

scholarly journals Candida albicans Impacts Staphylococcus aureus Alpha-Toxin Production via Extracellular Alkalinization

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Olivia A. Todd ◽  
Mairi C. Noverr ◽  
Brian M. Peters
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Quorum Sensing ◽  
Bacterial Pathogen ◽  
Toxin Production ◽  
Extracellular Ph ◽  
Morbidity And Mortality ◽  
Alpha Toxin ◽  
Content Type

ABSTRACT Candida albicans and Staphylococcus aureus are common causes of nosocomial infections with severe morbidity and mortality. Murine polymicrobial intra-abdominal infection (IAI) with C. albicans and S. aureus results in acute mortality dependent on the secreted cytolytic effector alpha-toxin. Here, we confirmed that alpha-toxin is elevated during polymicrobial growth compared to monomicrobial growth in vitro. Therefore, this study sought to unravel the mechanism by which C. albicans drives enhanced staphylococcal alpha-toxin production. Using a combination of functional and genetic approaches, we determined that an intact agr quorum sensing regulon is necessary for enhanced alpha-toxin production during coculture and that a secreted candidal factor likely is not implicated in elevating agr activation. As the agr system is pH sensitive, we observed that C. albicans raises the pH during polymicrobial growth and that this correlates with increased agr activity and alpha-toxin production. Modulation of the pH could predictably attenuate or activate agr activity during coculture. By using a C. albicans mutant deficient in alkalinization (stp2Δ/Δ), we confirmed that modulation of the extracellular pH by C. albicans can drive agr expression and toxin production. Additionally, the use of various Candida species (C. glabrata, C. dubliniensis, C. tropicalis, C. parapsilosis, and C. krusei) demonstrated that those capable of raising the extracellular pH correlated with elevated agr activity and alpha-toxin production during coculture. Overall, we demonstrate that alkalinization of the extracellular pH by the Candida species leads to sustained activation of the staphylococcal agr system. IMPORTANCE Candida albicans and Staphylococcus aureus are commonly coisolated from central venous catheters and deep-seated infections, including intra-abdominal sepsis. Thus, they represent a significant cause of nosocomial morbidity and mortality. Yet how these organisms behave in the context of polymicrobial growth remains poorly understood. In this work, we set out to determine the mechanism by which activation of the staphylococcal agr quorum sensing system and production of its major virulence effector alpha-toxin is enhanced during coculture with C. albicans. Surprisingly, we likely ruled out that a secreted candidal factor drives this process. Instead, we demonstrated that alkalinization of the extracellular milieu by C. albicans and other Candida species correlated with elevated agr activity. Thus, we propose a mechanism where modulation of the extracellular pH by fungal opportunists can indirectly alter virulence of a bacterial pathogen. Uncovering molecular events that drive interkingdom pathogenicity mechanisms may enhance surveillance and treatment for devastating polymicrobial infections.

scholarly journals Disruption of Glycolysis by Nutritional Immunity Activates a Two-Component System That Coordinates a Metabolic and Antihost Response by Staphylococcus aureus

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Paola K. Párraga Solórzano ◽  
Jiangwei Yao ◽  
Charles O. Rock ◽  
Thomas E. Kehl-Fie
Keyword(s):  
Staphylococcus Aureus ◽  
Metabolic Flux ◽  
Bacterial Species ◽  
Critical Role ◽  
Dependent Manner ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Nutritional Immunity ◽  
Two Component

ABSTRACT During infection, bacteria use two-component signal transduction systems to sense and adapt to the dynamic host environment. Despite critically contributing to infection, the activating signals of most of these regulators remain unknown. This also applies to the Staphylococcus aureus ArlRS two-component system, which contributes to virulence by coordinating the production of toxins, adhesins, and a metabolic response that enables the bacterium to overcome host-imposed manganese starvation. Restricting the availability of essential transition metals, a strategy known as nutritional immunity, constitutes a critical defense against infection. In this work, expression analysis revealed that manganese starvation imposed by the immune effector calprotectin or by the absence of glycolytic substrates activates ArlRS. Manganese starvation imposed by calprotectin also activated the ArlRS system even when glycolytic substrates were present. A combination of metabolomics, mutational analysis, and metabolic feeding experiments revealed that ArlRS is activated by alterations in metabolic flux occurring in the latter half of the glycolytic pathway. Moreover, calprotectin was found to induce expression of staphylococcal leukocidins in an ArlRS-dependent manner. These studies indicated that ArlRS is a metabolic sensor that allows S. aureus to integrate multiple environmental stresses that alter glycolytic flux to coordinate an antihost response and to adapt to manganese starvation. They also established that the latter half of glycolysis represents a checkpoint to monitor metabolic state in S. aureus. Altogether, these findings contribute to understanding how invading pathogens, such as S. aureus, adapt to the host during infection and suggest the existence of similar mechanisms in other bacterial species. IMPORTANCE Two-component regulatory systems enable bacteria to adapt to changes in their environment during infection by altering gene expression and coordinating antihost responses. Despite the critical role of two-component systems in bacterial survival and pathogenesis, the activating signals for most of these regulators remain unidentified. This is exemplified by ArlRS, a Staphylococcus aureus global regulator that contributes to virulence and to resisting host-mediated restriction of essential nutrients, such as manganese. In this report, we demonstrate that manganese starvation and the absence of glycolytic substrates activate ArlRS. Further investigations revealed that ArlRS is activated when the latter half of glycolysis is disrupted, suggesting that S. aureus monitors flux through the second half of this pathway. Host-imposed manganese starvation also induced the expression of pore-forming toxins in an ArlRS-dependent manner. Cumulatively, this work reveals that ArlRS acts as a sensor that links nutritional status, cellular metabolism, and virulence regulation.

scholarly journals Inhibition of Staphylococcus aureus Invasion into Bovine Mammary Epithelial Cells by Contact with Live Lactobacillus casei

2012 ◽  
Vol 79 (3) ◽  
pp. 877-885 ◽  
Author(s):  
Damien S. Bouchard ◽  
Lucie Rault ◽  
Nadia Berkova ◽  
Yves Le Loir ◽  
Sergine Even
Keyword(s):  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Lactobacillus Casei ◽  
Mammary Epithelial Cells ◽  
Control Strategies ◽  
Mammary Epithelial ◽  
Dairy Herds ◽  
Dependent Manner ◽  
Content Type ◽  
Bovine Mammary Epithelial Cells

ABSTRACTStaphylococcus aureusis a major pathogen that is responsible for mastitis in dairy herds.S. aureusmastitis is difficult to treat and prone to recurrence despite antibiotic treatment. The ability ofS. aureusto invade bovine mammary epithelial cells (bMEC) is evoked to explain this chronicity. One sustainable alternative to treat or prevent mastitis is the use of lactic acid bacteria (LAB) as mammary probiotics. In this study, we tested the ability ofLactobacillus caseistrains to prevent invasion of bMEC by twoS. aureusbovine strains, RF122 and Newbould305, which reproducibly induce acute and moderate mastitis, respectively.L. caseistrains affected adhesion and/or internalization ofS. aureusin a strain-dependent manner. Interestingly,L. caseiCIRM-BIA 667 reducedS. aureusNewbould305 and RF122 internalization by 60 to 80%, and this inhibition was confirmed for two otherL. caseistrains, including one isolated from bovine teat canal. The protective effect occurred without affecting bMEC morphology and viability. Once internalized, the fate ofS. aureuswas not affected byL. casei. It should be noted thatL. caseiwas internalized at a low rate but survived in bMEC cells with a better efficiency than that ofS. aureusRF122. Inhibition ofS. aureusadhesion was maintained with heat-killedL. casei, whereas contact between liveL. caseiandS. aureusor bMEC was required to preventS. aureusinternalization. This first study of the antagonism of LAB towardS. aureusin a mammary context opens avenues for the development of novel control strategies against this major pathogen.

scholarly journals Eradication of Methicillin-Resistant Staphylococcus aureus and of Enterobacteriaceae Expressing Extended-Spectrum Beta-Lactamases on a Model Pig Farm

2015 ◽  
Vol 81 (21) ◽  
pp. 7633-7643 ◽  
Author(s):  
Ricarda Maria Schmithausen ◽  
Sophia Ricarda Kellner ◽  
Sophia Veronika Schulze-Geisthoevel ◽  
Sylvia Hack ◽  
Steffen Engelhart ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Present Report ◽  
Protein A ◽  
Complete Removal ◽  
Drug Resistant ◽  
Methicillin Resistant ◽  
Content Type ◽  
Extended Spectrum ◽  
Extended Spectrum Beta Lactamases ◽  
Mrsa Strains

ABSTRACTColonization of livestock with bacteria resistant to antibiotics is considered a risk for the entry of drug-resistant pathogens into the food chain. For this reason, there is a need for novel concepts to address the eradication of drug-resistant commensals on farms. In the present report, we evaluated the decontamination measures taken on a farm contaminated with methicillin-resistantStaphylococcus aureus(MRSA) andEnterobacteriaceaeexpressing extended-spectrum β-lactamases (ESBL-E). The decontamination process preceded the conversion from piglet breeding to gilt production. Microbiological surveillance showed that the decontamination measures eliminated the MRSA and ESBL-E strains that were detected on the farm before the complete removal of pigs, cleaning and disinfection of the stable, and construction of an additional stable meeting high-quality standards. After pig production was restarted, ESBL-E remained undetectable over 12 months, but MRSA was recovered from pigs and the environment within the first 2 days. However,spa(Staphylococcus aureusprotein A gene) typing revealed acquisition of an MRSA strain (type t034) that had not been detected before decontamination. Interestingly, we observed that a farmworker who had been colonized with the prior MRSA strain (t2011) acquired the new strain (t034) after 2 months. In summary, this report demonstrates that decontamination protocols similar to those used here can lead to successful elimination of contaminating MRSA and ESBL-E in pigs and the stable environment. Nevertheless, decontamination protocols do not prevent the acquisition of new MRSA strains.

scholarly journals Four-Component Staphylococcus aureus Vaccine 4C-Staph Enhances Fcγ Receptor Expression in Neutrophils and Monocytes and Mitigates S. aureus Infection in Neutropenic Mice

2015 ◽  
Vol 83 (8) ◽  
pp. 3157-3163 ◽  
Author(s):  
Antonina Torre ◽  
Marta Bacconi ◽  
Chiara Sammicheli ◽  
Bruno Galletti ◽  
Donatello Laera ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Pathogen ◽  
Receptor Expression ◽  
Effective Vaccine ◽  
Infection Model ◽  
Fcγ Receptor ◽  
Air Pouch ◽  
Content Type ◽  
Specific Antibodies ◽  
Immune Correlates

Staphylococcus aureusis a human bacterial pathogen causing a variety of diseases. The occurrence of multidrug-resistant strains ofStaphylococcus aureusunderlines the need for a vaccine. Defining immune correlates of protection may support the design of an effective vaccine. We used a murineStaphylococcus aureusinfection model, in which bacteria were inoculated in an air pouch generated on the back of the animal. Analysis of the air-pouch content in mice immunized or not with an adjuvanted multiantigen vaccine formulation, four-componentS. aureusvaccine (4C-Staph), prior to infection allowed us to measure bacteria, cytokines, and 4C-Staph-specific antibodies and to analyze host immune cells recruited to the infection site. Immunization with 4C-Staph resulted in accumulation of antigen-specific antibodies in the pouch and mitigated the infection. Neutrophils were the most abundant cells in the pouch, and they showed the upregulation of Fcγ receptor (FcγR) following immunization with 4C-Staph. Reduction of the infection was also obtained in mice immunized with 4C-Staph and depleted of neutrophils; these mice showed an increase in monocytes and macrophages. Upregulation of the FcγR and the presence of antigen-specific antibodies induced by immunization with 4C-Staph may contribute to increase bacterial opsonophagocytosis. Protection in neutropenic mice indicated that an effective vaccine could activate alternative protection mechanisms compensating for neutropenia, a condition often occurring inS. aureus-infected patients.

scholarly journals Purified Streptococcus pneumoniae Endopeptidase O (PepO) Enhances Particle Uptake by Macrophages in a Toll-Like Receptor 2- and miR-155-Dependent Manner

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Hua Yao ◽  
Hong Zhang ◽  
Kai Lan ◽  
Hong Wang ◽  
Yufeng Su ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Host Defense ◽  
Defense Response ◽  
Dependent Manner ◽  
Toll Like Receptor ◽  
Content Type ◽  
Host Defense Response ◽  
Toll Like Receptor 2 ◽  
In Cells

ABSTRACT Insights into the host-microbial virulence factor interaction, especially the immune signaling mechanisms, could provide novel prevention and treatment options for pneumococcal diseases. Streptococcus pneumoniae endopeptidase O (PepO) is a newly discovered and ubiquitously expressed pneumococcal virulence protein. A PepO-mutant strain showed impaired adherence to and invasion of host cells compared with the isogenic wild-type strain. It is still unknown whether PepO is involved in the host defense response to pneumococcal infection. Here, we demonstrated that PepO could enhance phagocytosis of Streptococcus pneumoniae and Staphylococcus aureus by peritoneal exudate macrophages (PEMs). Further studies showed that PepO stimulation upregulated the expression of microRNA-155 (miR-155) in PEMs in a time- and dose-dependent manner. PepO-induced enhanced phagocytosis was decreased in cells transfected with an inhibitor of miR-155, while it was increased in cells transfected with a mimic of miR-155. We also revealed that PepO-induced upregulation of miR-155 in PEMs was mediated by Toll-like receptor 2 (TLR2)–NF-κB signaling and that the increased expression of miR-155 downregulated expression of SHIP1. Taken together, these results indicate that PepO induces upregulation of miR-155 in PEMs, contributing to enhanced phagocytosis and host defense response to pneumococci and Staphylococcus aureus.

scholarly journals Complete Bypass of Restriction Systems for Major Staphylococcus aureus Lineages

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Ian R. Monk ◽  
Jai J. Tree ◽  
Benjamin P. Howden ◽  
Timothy P. Stinear ◽  
Timothy J. Foster
Keyword(s):  
Staphylococcus Aureus ◽  
Plasmid Dna ◽  
High Efficiency ◽  
Recombinant Dna ◽  
Genetic Manipulation ◽  
Bacterial Pathogen ◽  
Type I ◽  
Content Type ◽  
E Coli ◽  
Adenine Methylation

ABSTRACTStaphylococcus aureusis a prominent global nosocomial and community-acquired bacterial pathogen. A strong restriction barrier presents a major hurdle for the introduction of recombinant DNA into clinical isolates ofS. aureus. Here, we describe the construction and characterization of the IMXXB series ofEscherichia colistrains that mimic the type I adenine methylation profiles ofS. aureusclonal complexes 1, 8, 30, and ST93. The IMXXB strains enable direct, high-efficiency transformation and streamlined genetic manipulation of majorS. aureuslineages.IMPORTANCEThe genetic manipulation of clinicalS. aureusisolates has been hampered due to the presence of restriction modification barriers that detect and subsequently degrade inappropriately methylated DNA. Current methods allow the introduction of plasmid DNA into a limited subset ofS. aureusstrains at high efficiency after passage of plasmid DNA through the restriction-negative, modification-proficient strain RN4220. Here, we have constructed and validated a suite ofE. colistrains that mimic the adenine methylation profiles of different clonal complexes and show high-efficiency plasmid DNA transfer. The ability to bypass RN4220 will reduce the cost and time involved for plasmid transfer intoS. aureus. The IMXXB series ofE. colistrains should expedite the process of mutant construction in diverse genetic backgrounds and allow the application of new techniques to the genetic manipulation ofS. aureus.

scholarly journals MsaB and CodY Interact To RegulateStaphylococcus aureusCapsule in a Nutrient-Dependent Manner

2018 ◽  
Vol 200 (17) ◽  
Author(s):  
Justin L. Batte ◽  
Gyan S. Sahukhal ◽  
Mohamed O. Elasri
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Nutrient Sensing ◽  
Nutrient Concentrations ◽  
Dependent Manner ◽  
Regulatory Relationship ◽  
Content Type ◽  
Capsule Production ◽  
Branched Chain ◽  
Complex Regulatory Network

ABSTRACTStaphylococcus aureushas a complex regulatory network for controlling the production of capsule polysaccharide. InS. aureus, capsule production is controlled by several regulators in response to various environmental stimuli. Previously, we described MsaB as a new regulator that specifically binds to thecappromoter in a growth phase- or nutrient-dependent manner. In addition to MsaB, several other regulators have also been shown to bind the same region. In this study, we examined the interactions between MsaB and other nutrient-sensing regulators (CodY and CcpE) with respect to binding to thecappromoter in a nutrient-dependent manner. We observed thatmsaABCRandccpEinteract in a complex fashion to regulate capsule production. However, we confirmed thatccpEdoes not bindcapdirectly. We also defined the regulatory relationship betweenmsaABCRand CodY. When nutrients (branched-chain amino acids) are abundant, CodY binds to the promoter region of thecapoperon and represses its transcription. However, when nutrient concentrations decrease, MsaB, rather than CodY, binds to thecappromoter. Binding of MsaB to thecappromoter activates transcription of thecapoperon. We hypothesize that this same mechanism may be used byS. aureusto regulate other virulence factors.IMPORTANCEFindings from this study define the mechanism of regulation of capsule production inStaphylococcus aureus. Specifically, we show that two key regulators, MsaB and CodY, coordinate their functions to control the expression of capsule in response to nutrients.S. aureusfine-tunes the production of capsule by coordinating the activity of several regulators and by sensing nutrient levels. This study demonstrates the importance of incorporating multiple inputs prior to the expression of costly virulence factors, such as capsule.

scholarly journals Glycolytic Dependency of High-Level Nitric Oxide Resistance and Virulence in Staphylococcus aureus

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Nicholas P. Vitko ◽  
Nicole A. Spahich ◽  
Anthony R. Richardson
Keyword(s):  
Nitric Oxide ◽  
Staphylococcus Aureus ◽  
Innate Immunity ◽  
Bacterial Pathogen ◽  
No Production ◽  
Low Oxygen ◽  
Acid Fermentation ◽  
Independent Manner ◽  
Content Type ◽  
The Impact

ABSTRACTStaphylococcus aureusis a prolific human pathogen capable of causing severe invasive disease with a myriad of presentations. The ability ofS. aureusto cause infection is strongly linked with its capacity to overcome the effects of innate immunity, whether by directly killing immune cells or expressing factors that diminish the impact of immune effectors. One such scenario is the induction of lactic acid fermentation byS. aureusin response to host nitric oxide (NO·). This fermentative activity allowsS. aureusto balance redox during NO·-induced respiration inhibition. However, little is known about the metabolic substrates and pathways that support this activity. Here, we identify glycolytic hexose catabolism as being essential forS. aureusgrowth in the presence of high levels of NO·. We determine that glycolysis supportsS. aureusNO· resistance by allowing for ATP and precursor metabolite production in a redox-balanced and respiration-independent manner. We further demonstrate that glycolysis is required for NO· resistance during phagocytosis and that increased levels of extracellular glucose limit the effectiveness of phagocytic killing by enhancing NO· resistance. Finally, we demonstrate thatS. aureusglycolysis is essential for virulence in both sepsis and skin/soft tissue models of infection in a time frame consistent with the induction of innate immunity and host NO· production.IMPORTANCEStaphylococcus aureusis a leading human bacterial pathogen capable of causing a wide variety of diseases that, as a result of antibiotic resistance, are very difficult to treat. The frequency ofS. aureustissue invasion suggests that this bacterium has evolved to resist innate immunity and grow using the nutrients present in otherwise sterile host tissue. We have identified glycolysis as an essential component ofS. aureusvirulence and attribute its importance to promoting nitric oxide resistance and growth under low oxygen conditions. Our data suggest that diabetics, a patient population characterized by excess serum glucose, may be more susceptible toS. aureusas a result of increased glucose availability. Furthermore, the essential nature ofS. aureusglycolysis indicates that a newly developed glycolysis inhibitor may be a highly effective treatment forS. aureusinfections.

Sign in / Sign up

Export Citation Format

Share Document