8 results on '"Dumont, Ashley"'
Search Results
2. Author response: Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress
- Author
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Podkowik, Magdalena, primary, Perault, Andrew, additional, Putzel, Gregory, additional, Pountain, Andrew, additional, Kim, Jisun, additional, DuMont, Ashley, additional, Zwack, Erin, additional, Ulrich, Robert, additional, Kargounis, Theodora, additional, Zhou, Chunyi, additional, Haag, Andreas, additional, Shenderovich, Julia, additional, Wasserman, Gregory, additional, Kwon, Junbeom, additional, Chen, John, additional, Richardson, Anthony Robert, additional, Weiser, Jeff, additional, Nowosad, Carla, additional, Lun, Desmond, additional, Parker, Dane, additional, Pironti, Alejandro, additional, Zhao, Xilin, additional, Drlica, Karl, additional, Yanai, Itai, additional, Torres, Victor J, additional, and Shopsin, Bo, additional
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- 2024
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3. Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress
- Author
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Podkowik, Magdalena, primary, Perault, Andrew I., additional, Putzel, Gregory, additional, Pountain, Andrew, additional, Kim, Jisun, additional, Dumont, Ashley, additional, Zwack, Erin, additional, Ulrich, Robert J., additional, Karagounis, Theodora K., additional, Zhou, Chunyi, additional, Haag, Andreas F., additional, Shenderovich, Julia, additional, Wasserman, Gregory A., additional, Kwon, Junbeom, additional, Chen, John, additional, Richardson, Anthony R., additional, Weiser, Jeffrey N., additional, Nowosad, Carla R., additional, Lun, Desmond S., additional, Parker, Dane, additional, Pironti, Alejandro, additional, Zhao, Xilin, additional, Drlica, Karl, additional, Yanai, Itai, additional, Torres, Victor J., additional, and Shopsin, Bo, additional
- Published
- 2024
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4. Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.
- Author
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Podkowik, Magdalena, Perault, Andrew I., Putzel, Gregory, Pountain, Andrew, Jisun Kim, DuMont, Ashley L., Zwack, Erin E., Ulrich, Robert J., Karagounis, Theodora K., Chunyi Zhou, Haag, Andreas F., Shenderovich, Julia, Wasserman, Gregory A., Junbeom Kwon, John Chen, Richardson, Anthony R., Weiser, Jeffrey N., Nowosad, Carla R., Lun, Desmond S., and Parker, Dane
- Published
- 2024
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5. Prospective Randomized, Double-Blind, Placebo-Controlled Study of a Standardized Oral Pomegranate Extract on the Gut Microbiome and Short-Chain Fatty Acids.
- Author
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Sivamani, Raja K., Chakkalakal, Mincy, Pan, Adrianne, Nadora, Dawnica, Min, Mildred, Dumont, Ashley, Burney, Waqas A., and Chambers, Cindy J.
- Subjects
SHORT-chain fatty acids ,GUT microbiome ,POMEGRANATE ,MICROBIAL metabolites ,ANTHOCYANINS ,ELLAGIC acid ,MICROBIAL diversity - Abstract
Punica granatum L., commonly known as the pomegranate, is an abundant source of polyphenols, including hydrolyzable ellagitannins, ellagic acid, anthocyanins, and other bioactive phytochemicals shown to be effective in defending against oxidative stress, and has immunomodulatory activities. Ellagitannins, and their hydrolyzed product ellagic acid, interact with the gut microbiota to yield secondary metabolites known as urolithins that may have health benefits. The objective of this study was to determine the effects of supplementation with a standardized punicalagin-enriched pomegranate extract, Pomella
® (250 mg), on the gut microbiome, circulating short-chain fatty acids, and gut microbial-derived ellagitannin metabolite urolithins. A randomized, double-blind, placebo-controlled study was conducted over 4 weeks on healthy volunteers aged 25–55 years. Subjects were randomly assigned to receive either an oral supplement containing 75 mg of punicalagin or an oral placebo. Stool sample collection and venipuncture were performed to analyze the gut microbiome, SCFAs, and urolithin. There was no significant change in the gut microbial diversity in both cohorts after 4 weeks of intervention, but there was a significantly increased relative abundance of Coprococcus eutectus, Roseburia faecis, Roseburia inullnivorans, Ruminococcus bicirculans, Ruminococcus calidus, and Faecalibacterium prausnitzii. Pomegranate extract (PE) supplementation led to the augmentation of circulating propionate levels (p = 0.02) and an increasing trend for acetate levels (p = 0.12). The pomegranate extract (PE) supplementation group had an increased level of circulating urolithins compared to the placebo group (6.6% vs. 1.1%, p = 0.13). PE supplementation correlated with shifts in the gut microbiome and with higher circulating levels of propionate and acetate. Further studies should explore the implications in larger cohorts and over a longer duration. [ABSTRACT FROM AUTHOR]- Published
- 2024
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6. SARS-CoV-2 infection predisposes patients to coinfection with Staphylococcus aureus .
- Author
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Lubkin A, Bernard-Raichon L, DuMont AL, Valero Jimenez AM, Putzel GG, Gago J, Zwack EE, Olusanya O, Boguslawski KM, Dallari S, Dyzenhaus S, Herrmann C, Ilmain JK, Isom GL, Pawline M, Perault AI, Perelman S, Sause WE, Shahi I, St John A, Tierce R, Zheng X, Zhou C, Noval MG, O'Keeffe A, Podkowik M, Gonzales S, Inglima K, Desvignes L, Hochman SE, Stapleford KA, Thorpe LE, Pironti A, Shopsin B, Cadwell K, Dittmann M, and Torres VJ
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- Humans, Animals, Mice, Phylogeny, Female, New York City epidemiology, Male, Virulence, Middle Aged, Whole Genome Sequencing, Bacteremia microbiology, Disease Models, Animal, Aged, COVID-19 complications, COVID-19 microbiology, Coinfection microbiology, Coinfection virology, Staphylococcus aureus genetics, Staphylococcus aureus pathogenicity, Staphylococcal Infections microbiology, SARS-CoV-2 genetics
- Abstract
Severe COVID-19 has been associated with coinfections with bacterial and fungal pathogens. Notably, patients with COVID-19 who develop Staphylococcus aureus bacteremia exhibit higher rates of mortality than those infected with either pathogen alone. To understand this clinical scenario, we collected and examined S. aureus blood and respiratory isolates from a hospital in New York City during the early phase of the pandemic from both SARS-CoV-2+ and SARS-CoV-2- patients. Whole genome sequencing of these S. aureus isolates revealed broad phylogenetic diversity in both patient groups, suggesting that SARS-CoV-2 coinfection was not associated with a particular S. aureus lineage. Phenotypic characterization of the contemporary collection of S. aureus isolates from SARS-CoV-2+ and SARS-CoV-2- patients revealed no notable differences in several virulence traits examined. However, we noted a trend toward overrepresentation of S. aureus bloodstream strains with low cytotoxicity in the SARS-CoV-2+ group. We observed that patients coinfected with SARS-CoV-2 and S. aureus were more likely to die during the acute phase of infection when the coinfecting S. aureus strain exhibited high or low cytotoxicity. To further investigate the relationship between SARS-CoV-2 and S. aureus infections, we developed a murine coinfection model. These studies revealed that infection with SARS-CoV-2 renders mice susceptible to subsequent superinfection with low cytotoxicity S. aureus . Thus, SARS-CoV-2 infection sensitizes the host to coinfections, including S. aureus isolates with low intrinsic virulence., Importance: The COVID-19 pandemic has had an enormous impact on healthcare across the globe. Patients who were severely infected with SARS-CoV-2, the virus causing COVID-19, sometimes became infected with other pathogens, which is termed coinfection. If the coinfecting pathogen is the bacterium Staphylococcus aureus , there is an increased risk of patient death. We collected S. aureus strains that coinfected patients with SARS-CoV-2 to study the disease outcome caused by the interaction of these two important pathogens. We found that both in patients and in mice, coinfection with an S. aureus strain lacking toxicity resulted in more severe disease during the early phase of infection, compared with infection with either pathogen alone. Thus, SARS-CoV-2 infection can directly increase the severity of S. aureus infection., Competing Interests: V.J.T. has consulted for Janssen Research & Development, LLC, and has received honoraria from Genentech and Medimmune. He is also an inventor on patents and patent applications filed by New York University, which are currently under commercial license to Janssen Biotech Inc. Janssen Biotech Inc. had provided research funding and other payments associated with a licensing agreement. B.S. has consulted for Regeneron and MicroGenDx. K.C. has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie. R.T. completed a NYU-Regeneron postdoctoral training program in laboratory animal medicine.
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- 2024
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7. Microbiota and metabolic adaptation shape Staphylococcus aureus virulence and antimicrobial resistance during intestinal colonization.
- Author
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Zhou C, Pawline MB, Pironti A, Morales SM, Perault AI, Ulrich RJ, Podkowik M, Lejeune A, DuMont A, Stubbe FX, Korman A, Jones DR, Schluter J, Richardson AR, Fey PD, Drlica K, Cadwell K, Torres VJ, and Shopsin B
- Abstract
Depletion of microbiota increases susceptibility to gastrointestinal colonization and subsequent infection by opportunistic pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). How the absence of gut microbiota impacts the evolution of MRSA is unknown. The present report used germ-free mice to investigate the evolutionary dynamics of MRSA in the absence of gut microbiota. Through genomic analyses and competition assays, we found that MRSA adapts to the microbiota-free gut through sequential genetic mutations and structural changes that enhance fitness. Initially, these adaptations increase carbohydrate transport; subsequently, evolutionary pathways largely diverge to enhance either arginine metabolism or cell wall biosynthesis. Increased fitness in arginine pathway mutants depended on arginine catabolic genes, especially nos and arcC , which promote microaerobic respiration and ATP generation, respectively. Thus, arginine adaptation likely improves redox balance and energy production in the oxygen-limited gut environment. Findings were supported by human gut metagenomic analyses, which suggest the influence of arginine metabolism on colonization. Surprisingly, these adaptive genetic changes often reduced MRSA's antimicrobial resistance and virulence. Furthermore, resistance mutation, typically associated with decreased virulence, also reduced colonization fitness, indicating evolutionary trade-offs among these traits. The presence of normal microbiota inhibited these adaptations, preserving MRSA's wild-type characteristics that effectively balance virulence, resistance, and colonization fitness. The results highlight the protective role of gut microbiota in preserving a balance of key MRSA traits for long-term ecological success in commensal populations, underscoring the potential consequences on MRSA's survival and fitness during and after host hospitalization and antimicrobial treatment., Competing Interests: CONFLICTS OF INTERESTS B.S. has consulted for Basilea Pharmaceutica. V.J.T. has received honoraria from Pfizer and MedImmune and is an inventor on patents and patent applications filed by New York University, which are currently under commercial license to Janssen Biotech Inc. Janssen Biotech Inc. provides research funding and other payments associated with a licensing agreement. K.C. has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and AbbVie, consulted for or received honoraria from Vedanta, Genentech, and AbbVie, and is an inventor on US patent 10,722,600 and pro- visional patents 62/935,035 and 63/157,225. J.S. holds equity in Postbiotics Plus Research, has filed intellectual property applications related to the microbiome (reference numbers #63/299,607), and is on an advisory board and holds equity of Jona Health.
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- 2024
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8. Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.
- Author
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Podkowik M, Perault AI, Putzel G, Pountain A, Kim J, Dumont A, Zwack E, Ulrich RJ, Karagounis TK, Zhou C, Haag AF, Shenderovich J, Wasserman GA, Kwon J, Chen J, Richardson AR, Weiser JN, Nowosad CR, Lun DS, Parker D, Pironti A, Zhao X, Drlica K, Yanai I, Torres VJ, and Shopsin B
- Abstract
The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H
2 O2 , a crucial host defense against S. aureus . We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr increased both respiration and fermentation but decreased ATP levels and growth, suggesting that Δ agr cells assume a hyperactive metabolic state in response to reduced metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δ agr strains to lethal H2 O2 doses. Increased survival of wild-type agr cells during H2 O2 exposure required sodA , which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δ agr cells from killing by H2 O2 . Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived "memory" of agr -mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Nox2-/- ) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage., Competing Interests: Potential competing interests. B.S. has consulted for Basilea Pharmaceutica. V.J.T. has received honoraria from Pfizer and MedImmune, and is an inventor on patents and patent applications filed by New York University, which are currently under commercial license to Janssen Biotech Inc. Janssen Biotech Inc. provides research funding and other payments associated with a licensing agreement. All other authors: no competing interests declared.- Published
- 2024
- Full Text
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