Publications by authors named "Wargo M"

Sphingoid bases, including sphingosine, are important components of the antimicrobial barrier at epithelial surfaces where they can cause growth inhibition and killing of susceptible bacteria. is a common opportunistic pathogen that is less susceptible to sphingosine than many Gram-negative bacteria. Here, we determined that the deletion of the operon reduced growth in the presence of sphingosine.

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Sphingoid bases, including sphingosine, are important components of the antimicrobial barrier at epithelial surfaces where they can cause growth inhibition and killing of susceptible bacteria. is a common opportunistic pathogen that is less susceptible to sphingosine than many Gram-negative bacteria. Here, we determined that deletion of the operon reduced growth in the presence of sphingosine.

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Unlabelled: Hemolytic phospholipase C, PlcH, is an important virulence factor for . PlcH preferentially hydrolyzes sphingomyelin and phosphatidylcholine, and this hydrolysis activity drives tissue damage and inflammation and interferes with the oxidative burst of immune cells. Among other contributors, transcription of was previously shown to be induced by phosphate starvation via PhoB and the choline metabolite, glycine betaine, via GbdR.

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Despite significant progress in recent decades toward ameliorating the excess burden of diarrheal disease globally, childhood diarrhea remains a leading cause of morbidity and mortality in low-and-middle-income countries (LMICs). Recent large-scale studies of diarrhea etiology in these populations have revealed widespread co-infection with multiple enteric pathogens, in both acute and asymptomatic stool specimens. We applied methods from network science and ecology to better understand the underlying structure of enteric co-infection among infants in two large longitudinal birth cohorts in Bangladesh.

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Background: An emerging strategy to treat symptoms of gastrointestinal (GI) dysmotility utilizes the administration of isolated bacteria. However, the underlying mechanisms of action of these bacterial agents are not well established. Here, we elucidate a novel approach to promote intestinal motility by exploiting the biochemical capability of specific bacteria to produce the serotonin (5-HT) precursor, tryptophan (Trp).

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Aggregatibacter actinomycetemcomitans is a gram-negative bacterium associated with periodontal disease and a variety of disseminated extra-oral infections. Tissue colonization is mediated by fimbriae and non-fimbriae adhesins resulting in the formation of a sessile bacterial community or biofilm, which confers enhanced resistance to antibiotics and mechanical removal. The environmental changes experienced by A.

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Article Synopsis
  • * The interaction between these two ISS strains shows enhanced biofilm formation that is influenced by factors like starting inoculum and temperature but varies depending on growth media and does not appear to involve soluble mediators.
  • * Although the study improves knowledge about these bacteria in biofilm formation, the enhanced interactions observed in ISS strains are not necessarily applicable to similar strains found on Earth.
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Background: Dysregulation of gut microbiota-associated tryptophan metabolism has been observed in patients with multiple sclerosis. However, defining direct mechanistic links between this apparent metabolic rewiring and individual constituents of the gut microbiota remains challenging. We and others have previously shown that colonization with the gut commensal and putative probiotic species, Lactobacillus reuteri, unexpectedly enhances host susceptibility to experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis.

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Glutamine amidotransferase-1 domain-containing AraC-family transcriptional regulators (GATRs) are present in the genomes of many bacteria, including all species. The involvement of several characterized GATRs in amine-containing compound metabolism has been determined, but the full scope of GATR ligands and regulatory networks are still unknown. Here, we characterize 's detection of the animal-derived amine compound creatine, a compound particularly enriched in muscle and ciliated cells by a creatine-specific GATR, PP_3665, here named CahR (Creatine amidohydrolase Regulator).

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Obesity alters the risks and outcomes of inflammatory lung diseases. It is important to accurately recapitulate the obese state in animal models to understand these effects on the pathogenesis of disease. Diet-induced obesity is a commonly used model of obesity, but when applied to other disease models like acute respiratory distress syndrome, pneumonia, and asthma, it yields widely divergent.

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By integrating various simulation and experimental techniques, we discovered that antimicrobial peptides (AMPs) may achieve synergy at an optimal concentration and ratio, which can be caused by aggregation of the synergistic peptides. On multiple time and length scales, our studies obtain novel evidence of how peptide coaggregation in solution can affect the disruption of membranes by synergistic AMPs. Our findings provide crucial details about the complex molecular origins of AMP synergy, which will help guide the future development of synergistic AMPs as well as applications of anti-infective peptide cocktail therapies.

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Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical bronchoalveolar lavage fluid (BALF) samples, as a surrogate for the in vivo clinical lung environment, on MSC viability, gene expression, secreted cytokines, and mitochondrial function were compared with effects of BALF collected from healthy volunteers.

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Bacterial biofilms play a critical role in environmental processes, water treatment, human health, and food processing. They exhibit highly complex dynamics due to the interactions between the bacteria and the extracellular polymeric substance (EPS), water, and nutrients and minerals that make up the biofilm. We present a hybrid computational model in which the dynamics of discrete bacterial cells are simulated within a multiphase continuum, consisting of EPS and water as separate interacting phases, through which nutrients and minerals diffuse.

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Microbial biofilms are ubiquitous in drinking water systems, yet our understanding of drinking water biofilms lags behind our understanding of those in other environments. Here, a six-member model bacterial community was used to identify the interactions and individual contributions of each species to community biofilm formation. These bacteria were isolated from the International Space Station potable water system and include , , , ( and , but all six species are common members of terrestrial potable water systems.

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Mesenchymal stromal (stem) cells (MSCs) are increasingly demonstrated to ameliorate experimentally induced lung injuries through disease-specific anti-inflammatory actions, thus suggesting that different in vivo inflammatory environments can influence MSC actions. To determine the effects of different representative inflammatory lung conditions, human bone marrow-derived MSCs (hMSCs) were exposed to in vitro culture conditions from bronchoalveolar lavage fluid (BALF) samples obtained from patients with either the acute respiratory distress syndrome (ARDS) or with other lung diseases including acute respiratory exacerbations of cystic fibrosis (CF) (non-ARDS). hMSCs were subsequently assessed for time- and BALF concentration-dependent effects on mRNA expression of selected pro- and anti-inflammatory mediators, and for overall patterns of gene and mRNA expression.

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People with cystic fibrosis are susceptible to lung infections from a variety of bacteria, a number of which also reside in the potable water system, including , , , complex, and nontuberculosis Here, I propose chemical and physical aspects of the potable water system along with bacterial lifestyle strategies in this system that may enhance successful colonization of cystic fibrosis lungs by these bacteria, including iron and copper levels, lipids, and low growth rates within low-oxygen biofilms.

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Article Synopsis
  • The study focuses on characterizing the transcriptional responses of a Gram-negative pathogen found in cystic fibrosis (CF) lungs when exposed to a synthetic medium that simulates CF sputum.
  • Researchers identified 881 differentially expressed transcripts across three strains, highlighting metabolic pathways and stress responses, particularly increased peroxide resistance after exposure to the sputum medium.
  • The findings also revealed specific gene expression changes related to biofilm formation, particularly in the K279a strain, suggesting adaptations that enhance survival during CF lung infections.
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Introduction: The measurement of specific volatile organic compounds in breath has been proposed as a potential diagnostic for a variety of diseases. The most well-studied bacterial lung infection in the breath field is that caused by Pseudomonas aeruginosa.

Objectives: To determine a discriminatory core of molecules in the "breath-print" of mice during a lung infection with four strains of P.

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Stenotrophomonas maltophilia is an opportunistic pathogen causing airway infection in people with cystic fibrosis (CF). Here, we report the draft genome sequences of two S. maltophilia strains, AU30115 and AU32848, recovered from CF patients.

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Studies comparing endogenous and recombinant serum amyloid A (SAA) have generated conflicting data on the proinflammatory function of these proteins. In exploring this discrepancy, we found that in contrast to commercially sourced recombinant human SAA1 (hSAA1) proteins produced in , hSAA1 produced from eukaryotic cells did not promote proinflammatory cytokine production from human or mouse cells, induce Th17 differentiation, or stimulate TLR2. Proteomic analysis of -derived hSAA1 revealed the presence of numerous bacterial proteins, with several being reported or probable lipoproteins.

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The interactions between and the host environment at the site of infection are largely unknown. Pulmonary surfactant serves as an initial point of contact for inhaled bacteria entering the lung and is thought to contain molecular cues that aid colonization and pathogenesis. To gain insight into this ecological transition, we characterized the transcriptional response of MGH 78578 to purified pulmonary surfactant.

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The opportunistic pathogen Pseudomonas aeruginosa can metabolize carnitine and O-acylcarnitines, which are abundant in host muscle and other tissues. Acylcarnitines are metabolized to carnitine and a fatty acid. The liberated carnitine and its catabolic product, glycine betaine, can be used as osmoprotectants, to induce the secreted phospholipase C PlcH, and as sole carbon, nitrogen and energy sources.

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The common environmental bacterium and opportunistic pathogen encodes diverse metabolic pathways and associated regulatory networks allowing it to thrive in these different environments. In an effort to understand metabolism and detection of host-derived compounds, we previously identified CdhR and GbdR as members of the AraC transcription factor family that regulate catabolism of the quaternary amine compounds carnitine and glycine betaine, respectively. In this study, our goal was to further characterize regulation of carnitine catabolism by the transcription factor CdhR.

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Many infections are derived from residential, recreational, or surface water sources; thus, these environments represent an important preinfection niche. To better understand biology in these environments, we quantified transcriptional changes by microarray after exposure to diluted LB, diluted R2B, potable tap water, and freshwater from a eutrophic pond. Quantitative reverse transcription-PCR (qRT-PCR) confirmed the conservation of these responses in other water sources, and competition experiments were used to test the importance of three implicated metabolic pathways.

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The bacterial pathogen Pseudomonas aeruginosa undergoes adaptation and selection over the course of chronic respiratory tract infections which results in repeatedly-observed phenotypic changes that are proposed to enable its persistence. Two of the clinically significant P. aeruginosa phenotypic changes are loss of flagellar motility and modifications to LPS structure, including loss of O-antigen expression.

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