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Abstract Bacterial communities are integral constituents of tobacco products. They originate from tobacco plants and are acquired during manufacturing processes, where they play a role in the production of tobacco-specific nitrosamines.... more
Abstract Bacterial communities are integral constituents of tobacco products. They originate from tobacco plants and are acquired during manufacturing processes, where they play a role in the production of tobacco-specific nitrosamines. In addition, tobacco bacterial constituents may play an important role in the development of infectious and chronic diseases among users. Nevertheless, tobacco bacterial communities have been largely unexplored, and the influence of tobacco flavor additives such as menthol (a natural antimicrobial) on tobacco bacterial communities is unclear. To bridge this knowledge gap, time series experiments including 5 mentholated and non-mentholated commercially available cigarettes—Marlboro red (non-menthol), Marlboro menthol, Newport menthol box, Newport menthol gold, and Newport non-menthol—were conducted. Each brand was stored under three different temperature and relative humidity conditions. To characterize bacterial communities, total DNA was extracted on days 0 and 14. Resulting DNA was purified and subjected to PCR of the V3V4 region of the 16S rRNA gene, followed by sequencing on the Illumina HiSeq platform and analysis using the QIIME, phyloseq, metagenomeSeq, and DESeq software packages. Ordination analyses showed that the bacterial community composition of Marlboro cigarettes was different from that of Newport cigarettes. Additionally, bacterial profiles significantly differed between mentholated and non-mentholated Newports. Independently of storage conditions, tobacco brands were dominated by Proteobacteria , with the most dominant bacterial genera being Pseudomonas , unclassified Enterobacteriaceae , Bacillus , Erwinia , Sphingomonas , Acinetobacter , Agrobacterium , Staphylococcus , and Terribacillus . These data suggest that the bacterial communities of tobacco products differ across brands and that mentholation of tobacco can alter bacterial community composition of select brands. Key Points • Bacterial composition differed between the two brands of cigarettes. • Mentholation impacts cigarette microbiota. • Pseudomonas and Bacillus dominated the commercial cigarettes. Graphical abstract
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ABSTRACTBackgroundDespite ongoing improvements in regimens to prevent allograft rejection, most cardiac and other organ grafts eventually succumb to chronic vasculopathy, interstitial fibrosis, or endothelial changes, and eventually graft... more
ABSTRACTBackgroundDespite ongoing improvements in regimens to prevent allograft rejection, most cardiac and other organ grafts eventually succumb to chronic vasculopathy, interstitial fibrosis, or endothelial changes, and eventually graft failure. The events leading to chronic rejection are still poorly understood and the gut microbiota is a known driving force in immune dysfunction. We previously showed that gut microbiota dysbiosis profoundly influences the outcome of vascularized cardiac allografts and subsequently identified biomarker species associated with these differential graft outcomes.MethodsIn this study, we further detailed the multifaceted immunomodulatory properties of pro-tolerogenic and pro-inflammatory bacterial species over time, using our clinically relevant model of allogenic heart transplantation.ResultsIn addition to tracing longitudinal changes in the recipient gut microbiome over time, we observed thatBifidobacterium pseudolongum (Bifido)induced an early ant...
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ABSTRACTThe beneficial effects attributed to Bifidobacterium are thought to arise from their host immunomodulatory capabilities, which are likely to be species- and even strain-specific. However, their strain-specificity in direct and... more
ABSTRACTThe beneficial effects attributed to Bifidobacterium are thought to arise from their host immunomodulatory capabilities, which are likely to be species- and even strain-specific. However, their strain-specificity in direct and indirect immune modulation remain largely uncharacterized. We have shown that B. pseudolongum UMB-MBP-01, a murine isolate, is capable of suppressing inflammation and reducing fibrosis in vivo. To ascertain the mechanism driving this activity and to determine if it is specific to UMB-MBP-01, we compared it to B. pseudolongum type strain ATCC25526 of porcine origin using a combination of in vitro and in vivo experimentation and comparative genomics approaches. Despite many shared features, we demonstrate that these two strains possess distinct genetic repertoires in carbohydrate assimilation, differential activation signatures and cytokine responses in innate immune cells, and differential effects on lymph node morphology with unique local and systemic ...
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Abstract Bacterial communities are integral constituents of tobacco products. They originate from tobacco plants and are acquired during manufacturing processes, where they play a role in the production of tobacco-specific nitrosamines.... more
Abstract Bacterial communities are integral constituents of tobacco products. They originate from tobacco plants and are acquired during manufacturing processes, where they play a role in the production of tobacco-specific nitrosamines. In addition, tobacco bacterial constituents may play an important role in the development of infectious and chronic diseases among users. Nevertheless, tobacco bacterial communities have been largely unexplored, and the influence of tobacco flavor additives such as menthol (a natural antimicrobial) on tobacco bacterial communities is unclear. To bridge this knowledge gap, time series experiments including 5 mentholated and non-mentholated commercially available cigarettes—Marlboro red (non-menthol), Marlboro menthol, Newport menthol box, Newport menthol gold, and Newport non-menthol—were conducted. Each brand was stored under three different temperature and relative humidity conditions. To characterize bacterial communities, total DNA was extracted on days 0 and 14. Resulting DNA was purified and subjected to PCR of the V3V4 region of the 16S rRNA gene, followed by sequencing on the Illumina HiSeq platform and analysis using the QIIME, phyloseq, metagenomeSeq, and DESeq software packages. Ordination analyses showed that the bacterial community composition of Marlboro cigarettes was different from that of Newport cigarettes. Additionally, bacterial profiles significantly differed between mentholated and non-mentholated Newports. Independently of storage conditions, tobacco brands were dominated by Proteobacteria , with the most dominant bacterial genera being Pseudomonas , unclassified Enterobacteriaceae , Bacillus , Erwinia , Sphingomonas , Acinetobacter , Agrobacterium , Staphylococcus , and Terribacillus . These data suggest that the bacterial communities of tobacco products differ across brands and that mentholation of tobacco can alter bacterial community composition of select brands. Key Points • Bacterial composition differed between the two brands of cigarettes. • Mentholation impacts cigarette microbiota. • Pseudomonas and Bacillus dominated the commercial cigarettes. Graphical abstract
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Lipopolysaccharide (LPS) is the major component of the outer membrane of gram-negative bacteria and consists of three distinct structural domains: lipid A, a nonrepeating “core” oligosaccharide, and a distal repeated O-antigen... more
Lipopolysaccharide (LPS) is the major component of the outer membrane of gram-negative bacteria and consists of three distinct structural domains: lipid A, a nonrepeating “core” oligosaccharide, and a distal repeated O-antigen polysaccharide. This chapter discusses the structure of the three regions, in order, as they extend out from the outer membrane, focusing on regulated alterations, modifications, and/or substitutions. The biosynthetic enzymes are either constitutively active or regulated by a variety of two-component regulatory systems, including PhoR/PhoB, PmrA/PmrB and/or PhoP/PhoQ. Deletion of IpxT in Escherichia coli resulted in an increase in sensitivity to the cationic antimicrobial peptides (AMPs) polymyxin B, although experiments elucidating roles for lpxT in overall pathogenesis have yet to be undertaken. The chapter explores the regulation of one particular modification, that of phosphorylcholine (ChoP), on Haemophilus and Neisseria lipooligosaccharide (LOS). Regulation of LPS core biosynthesis is not well understood, although some of the regulatory mechanisms for biosynthesis of Kdo and inner and outer core are emerging. The current evidence based on genetic and biophysical interaction studies of the Lpt proteins supports the transenvelope model. Further studies into the regulation of LPS should help provide a link between signals in the environment and the resulting outer membrane composition that are likely to have the most impact on host-pathogen interactions.
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SummaryStrains of Pseudomonas aeruginosa (PA) isolated from the airways of cystic fibrosis patients constitutively add palmitate to lipid A, the membrane anchor of lipopolysaccharide. The PhoPQ regulated enzyme PagP is responsible for the... more
SummaryStrains of Pseudomonas aeruginosa (PA) isolated from the airways of cystic fibrosis patients constitutively add palmitate to lipid A, the membrane anchor of lipopolysaccharide. The PhoPQ regulated enzyme PagP is responsible for the transfer of palmitate from outer membrane phospholipids to lipid A. This enzyme had previously been identified in many pathogenic Gram‐negative bacteria, but in PA had remained elusive, despite abundant evidence that its lipid A contains palmitate. Using a combined genetic and biochemical approach, we identified PA1343 as the PA gene encoding PagP. Although PA1343 lacks obvious primary structural similarity with known PagP enzymes, the β‐barrel tertiary structure with an interior hydrocarbon ruler appears to be conserved. PA PagP transfers palmitate to the 3′ position of lipid A, in contrast to the 2 position seen with the enterobacterial PagP. Palmitoylated PA lipid A alters host innate immune responses, including increased resistance to some anti...
Research Interests: Microbiology, Cystic Fibrosis, Biology, Cytokines, Molecular Microbiology, and 15 moreInnate immunity, Medicine, Biological Sciences, Lipopolysaccharide, Phylogeny, Humans, Mutation, Antimicrobial Cationic Peptides, Pseudomonas Aeruginosa, Protein Conformation, Amino Acid Sequence, Lipid A, Molecular Sequence Data, Lipoylation, and Medical and Health Sciences
Research Interests: Microbiology, Chemistry, Biomedical Engineering, Biofilms, Chitosan, and 15 morePorifera, Orthopaedic, Medicine, Vancomycin, Biofilm, Mice, Animals, Staphylococcus aureus, Candida albicans, Drug Delivery Systems, Clinical Sciences, Sponge, Antifungal Agents, Musculoskeletal system, and Polyethylene Glycols
Staphylococcus aureus causes intramammary infections (IMIs), which are refractory to antibiotic treatment and frequently result in chronic mastitis. IMIs are the leading cause of conventional antibiotic use in dairy farms. Phage therapy... more
Staphylococcus aureus causes intramammary infections (IMIs), which are refractory to antibiotic treatment and frequently result in chronic mastitis. IMIs are the leading cause of conventional antibiotic use in dairy farms. Phage therapy represents an alternative to antibiotics to help better manage mastitis in cows, reducing the global spread of resistance. A mouse mastitis model of S. aureus IMI was used to study the efficacy of a new cocktail of five lytic S. aureus-specific phages (StaphLyse™), administered either via the intramammary (IMAM) route or intravenously (IV). The StaphLyse™ phage cocktail was stable in milk for up to one day at 37 °C and up to one week at 4 °C. The phage cocktail was bactericidal in vitro against S. aureus in a dose-dependent manner. A single IMAM injection of this cocktail given 8 h after infection reduced the bacterial load in the mammary glands of lactating mice infected with S. aureus, and as expected, a two-dose regimen was more effective. Prophyl...
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The beneficial effects attributed to Bifidobacterium are largely attributed to their immunomodulatory capabilities, which are likely to be species- and even strain-specific. However, their strain-specificity in direct and indirect immune... more
The beneficial effects attributed to Bifidobacterium are largely attributed to their immunomodulatory capabilities, which are likely to be species- and even strain-specific. However, their strain-specificity in direct and indirect immune modulation remain largely uncharacterized. We have shown that B. pseudolongum UMB-MBP-01, a murine isolate, is capable of suppressing inflammation and reducing fibrosis in vivo. To ascertain the mechanism driving this activity and to determine if it is specific to UMB-MBP-01, we compared it to B. pseudolongum type strain ATCC25526 of porcine origin using a combination of in vitro and in vivo experimentation and comparative genomics approaches. Despite many shared features, we demonstrate that these two strains possess distinct genetic repertoires in carbohydrate assimilation, differential activation signatures and cytokine responses in innate immune cells, and differential effects on lymph node morphology with unique local and systemic leukocyte dis...
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16S rRNA gene sequences of all samples presented by group. (XLS 255 kb)
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List of Supplementary Figures and Tables. Figure S1. Rarefaction curves for each product. Figure S2. PCoA analysis plots of weighted and unweighted Unifrac computed distances between cigarette products. Figure S3. Pseudomonas phylogenetic... more
List of Supplementary Figures and Tables. Figure S1. Rarefaction curves for each product. Figure S2. PCoA analysis plots of weighted and unweighted Unifrac computed distances between cigarette products. Figure S3. Pseudomonas phylogenetic tree. Figure S4. Actinobacter phylogenetic tree. Figure S5. Stenotrophomonas phylogenetic tree. Figure S6. Anoxybacillus phylogenetic tree. Figure S7. Deinococcus phylogenetic tree. Figure S8. Vagococcus phylogenetic tree. Figure S9. Thermus phylogenetic tree. Figure S10. Proteus phylogenetic tree. Table S1. OTUs at statistically significantly different relative abundances between mentholated Camel King and non-mentholated Camel King. FC denotes fold change. (DOCX 1485 kb)
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The etiology of vulvar lichen sclerosus (LS) remains unclear; however, alterations in cutaneous and gut microbiota may be contributing to the pathogenesis of this inflammatory condition. To explore this hypothesis, we conducted a pilot... more
The etiology of vulvar lichen sclerosus (LS) remains unclear; however, alterations in cutaneous and gut microbiota may be contributing to the pathogenesis of this inflammatory condition. To explore this hypothesis, we conducted a pilot case-control study, obtaining dermal swab and stool samples from prepubertal girls with vulvar LS (n = 5), girls with nonspecific vulvovaginitis (n = 5), and healthy controls (n = 3). Samples (n = 56) were subjected to total DNA extractions. Resulting DNA was purified, subjected to PCR (targeting the V3V4 region of the 16S rRNA gene), sequenced, and analyzed using QIIME, MetagenomeSeq, and DESeq2 software packages. Our findings showed that there were significant differences in the cutaneous and gut microbiotas of girls with LS compared to controls. On the skin, girls with LS had a statistically significantly higher relative abundance of Porphyromonas spp., Parvimonas spp., Peptoniphilus spp., Prevotella spp., Dialister spp., and Peptostreptococcus spp...
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Background Staphylococcus aureus is a leading cause of infectious morbidity and mortality in neonates. Few data exist on the association of the nasal microbiome and susceptibility to neonatal S. aureus colonization and infection. Methods... more
Background Staphylococcus aureus is a leading cause of infectious morbidity and mortality in neonates. Few data exist on the association of the nasal microbiome and susceptibility to neonatal S. aureus colonization and infection. Methods We performed 2 matched case–control studies (colonization cohort—neonates who did and did not acquire S. aureus colonization; bacteremia cohort—neonates who did [colonized neonates] and did not [controls] acquire S. aureus colonization and neonates with S. aureus bacteremia [bacteremic neonantes]). Neonates in 2 intensive care units were enrolled and matched on week of life at time of colonization or infection. Nasal samples were collected weekly until discharge and cultured for S. aureus, and the nasal microbiome was characterized using 16S rRNA gene sequencing. Results In the colonization cohort, 43 S. aureus–colonized neonates were matched to 82 controls. At 1 week of life, neonates who acquired S. aureus colonization had lower alpha diversity (W...
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Summary We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated,... more
Summary We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities.
Research Interests: Developmental Biology, Global Health, Biology, Built Environment, Metagenomics, and 15 moreMedicine, Antibiotic Resistance, Biological Sciences, NGS, Cell, Microbial Genetics, AMR, Antimicrobial resistance, Geospatial Analysis, Microbiome, BGC, De Novo Genome Assembly, Metagenome, Medical and Health Sciences, and Resistome
Even with antiretroviral therapy, children born to HIV-infected (HI) mothers are at a higher risk of early-life infections and morbidities including dental disease. The increased risk of dental caries in HI children suggest... more
Even with antiretroviral therapy, children born to HIV-infected (HI) mothers are at a higher risk of early-life infections and morbidities including dental disease. The increased risk of dental caries in HI children suggest immune-mediated changes in oral bacterial communities, however, the impact of perinatal HIV exposure on the oral microbiota remains unclear. We hypothesized that the oral microbiota of HI and perinatally HIV-exposed-but-uninfected (HEU) children will significantly differ from HIV-unexposed-and-uninfected (HUU) children. Saliva samples from 286 child-participants in Nigeria, aged ≤ 6 years, were analyzed using 16S rRNA gene sequencing. Perinatal HIV infection was significantly associated with community composition (HI vs. HUU—p = 0.04; HEU vs. HUU—p = 0.11) however, immune status had stronger impacts on bacterial profiles (p < 0.001). We observed age-stratified associations of perinatal HIV exposure on community composition, with HEU children differing from HUU...
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Research Interests: Microbiology, Pediatrics, Diversity, Gastroenterology, Biotechnology, and 15 moreCancer, Ecology, Cell Biology, Infectious Diseases, Medicine, Multidisciplinary, Neonatal Necrotizing Enterocolitis, Internal Medicine, Irritable Bowel Syndrome, PLoS one, Microbiome, Feces, PN, Parenteral Nutrition, and Dysbiosis
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Chronic rhinosinusitis is an inflammatory disorder in which the role of bacteria remains uncertain. While sinus outflow obstruction is often an initiating event, mucosal inflammation and dysbiosis may persist or develop in sinuses with... more
Chronic rhinosinusitis is an inflammatory disorder in which the role of bacteria remains uncertain. While sinus outflow obstruction is often an initiating event, mucosal inflammation and dysbiosis may persist or develop in sinuses with widely patent surgical openings. Understanding of the relationship between dysbiosis and chronic sinus inflammation is obfuscated by inter-individual microbiota variability and likely intra-individual temporal variation that has yet to be defined. In this study, long-term microbiota stability is investigated within surgically-opened maxillary sinuses of individuals with and without sinus inflammatory disease. Maxillary sinus swabs were performed in 35 subjects with longstanding maxillary antrostomies. Subjects with and without active chronic maxillary sinusitis were included. Repeat swabs were obtained from the same sinuses after a prolonged interval (mean 719 ± 383 days). Patients were categorized based on the inflammatory status of the sinus mucosa ...
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Here, we report the complete genome sequence of Bifidobacterium pseudolongum strain UMB-MBP-01, isolated from the feces of C57BL/6J mice. This strain was identified in microbiome profiling studies and associated with improved transplant... more
Here, we report the complete genome sequence of Bifidobacterium pseudolongum strain UMB-MBP-01, isolated from the feces of C57BL/6J mice. This strain was identified in microbiome profiling studies and associated with improved transplant outcome in a murine model of cardiac heterotypic transplantation.
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The nose, throat, and skin over the subclavian and femoral veins are the body sites which harbor the bacteria which most commonly cause health care-associated infection. We assessed the effect of nursing home residence on the microbiota... more
The nose, throat, and skin over the subclavian and femoral veins are the body sites which harbor the bacteria which most commonly cause health care-associated infection. We assessed the effect of nursing home residence on the microbiota of these body sites in older adults. We found that the microbiota composition of the different body sites was similar between nursing home and community participants, but we identified differences in relative abundance levels. We found remarkable similarities in the bacterial communities of different body sites in older adults who lived in nursing homes compared to those in the community among people who had not been on antibiotics for the past 3 months. We also found that the femoral skin microbiota had evidence of stool contamination in the nursing home residents, providing a rationale for improved skin hygiene. Taken together, it appears that the health care environment does not alter the microbiota to the extent that antibiotics do.
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Tobacco products, specifically cigarettes, are home to microbial ecosystems that may play an important role in the generation of carcinogenic tobacco-specific nitrosamines (TSNAs), as well as the onset of multiple adverse human health... more
Tobacco products, specifically cigarettes, are home to microbial ecosystems that may play an important role in the generation of carcinogenic tobacco-specific nitrosamines (TSNAs), as well as the onset of multiple adverse human health effects associated with the use of these products. Therefore, we conducted time-series experiments with five commercially available brands of cigarettes that were either commercially mentholated, custom-mentholated, user-mentholated, or non-mentholated. To mimic user storage conditions, the cigarettes were incubated for 14 days under three different temperatures and relative humidities (i.e., pocket, refrigerator, and room). Overall, 360 samples were collected over the course of 2 weeks and total DNA was extracted, PCR amplified for the V3V4 hypervariable region of the 16S rRNA gene and sequenced using Illumina MiSeq. A subset of samples (n = 32) was also analyzed via liquid chromatography with tandem mass spectrometry for two TSNAs: N'-nitrosonorn...
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There is a paucity of data regarding the microbial constituents of tobacco products and their impacts on public health. Moreover, there has been no comparative characterization performed on the bacterial microbiota associated with the... more
There is a paucity of data regarding the microbial constituents of tobacco products and their impacts on public health. Moreover, there has been no comparative characterization performed on the bacterial microbiota associated with the addition of menthol, an additive that has been used by tobacco manufacturers for nearly a century. To address this knowledge gap, we conducted bacterial community profiling on tobacco from user- and custom-mentholated/non-mentholated cigarette pairs, as well as a commercially-mentholated product. Total genomic DNA was extracted using a multi-step enzymatic and mechanical lysis protocol followed by PCR amplification of the V3-V4 hypervariable regions of the 16S rRNA gene from five cigarette products (18 cigarettes per product for a total of 90 samples): Camel Crush, user-mentholated Camel Crush, Camel Kings, custom-mentholated Camel Kings, and Newport Menthols. Sequencing was performed on the Illumina MiSeq platform and sequences were processed using th...
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Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) lung disease causes airway neutrophilia and hyperinflammation without effective bacterial clearance. We evaluated the immunostimulatory activities of lipid A, the membrane... more
Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) lung disease causes airway neutrophilia and hyperinflammation without effective bacterial clearance. We evaluated the immunostimulatory activities of lipid A, the membrane anchor of LPS, isolated from mutants of PA that synthesize structural variants, present in the airways of patients with CF, to determine if they correlate with disease severity and progression. In a subset of patients with a severe late stage of CF disease, a unique hepta-acylated lipid A, hepta-1855, is synthesized. In primary human cell cultures, we found that hepta-1855 functioned as a potent TLR4 agonist by priming neutrophil respiratory burst and stimulating strong IL-8 from monocytes and neutrophils. hepta-1855 also had a potent survival effect on neutrophils. However, it was less efficient in stimulating neutrophil granule exocytosis and also less potent in triggering proinflammatory TNF-α response from monocytes. In PA isolates that do not synth...
Research Interests: Immunology, Cystic Fibrosis, Biology, Medicine, Toll like receptor signaling, and 13 moreHumans, Chronic Disease, Pseudomonas aeruginosa, Lipopolysaccharides, Exocytosis, Disease Progression, Pseudomonas Aeruginosa, Acylation, Structure activity Relationship, Lipid A, Respiratory Burst, neutrophilia, and Opportunistic Infections
Research Interests: Microbiology, Biofilms, Genomics, Computational Biology, Comparative Genomics, and 15 moreCystic Fibrosis, Biology, Medicine, Biological Sciences, Humans, Mutation, Chronic Disease, Gene Order, Genotype, Microbial Sensitivity Tests, Bronchiectasis, Gene expression profiling, Molecular Sequence Data, alleles, and Medical and Health Sciences
With an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging. Patients with infection or colonization due to colistin-resistant A.... more
With an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging. Patients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry. Twenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate ...
Research Interests: Microbiology, Electronic Health Records, Medicine, Biological Sciences, Humans, and 15 moreFemale, Male, Aged, Middle Aged, Adult, Colistin, Carbapenem, Carbapenems, Microbial Sensitivity Tests, Ampicillin, Acinetobacter baumannii, Lipid A, Clinical Infectious Diseases, Acinetobacter Infections, and Medical and Health Sciences
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Pathogen transmission cycles require many steps: initial colonization, growth and persistence, shedding, and transmission to new hosts. Alterations in the membrane components of the bacteria, including lipid A, the membrane anchor of... more
Pathogen transmission cycles require many steps: initial colonization, growth and persistence, shedding, and transmission to new hosts. Alterations in the membrane components of the bacteria, including lipid A, the membrane anchor of lipopolysaccharide, could affect any of these steps via its structural role protecting bacteria from host innate immune defenses, including antimicrobial peptides and signaling through Toll-like receptor 4 (TLR4). To date, lipid A has been shown to affect only the within-host dynamics of infection, not the between-host dynamics of transmission. Here, we investigate the effects of lipid A modification in a mouse infection and transmission model. Disruption of the Bordetella bronchiseptica locus ( BB4268 ) revealed that ArnT is required for addition of glucosamine (GlcN) to B. bronchiseptica lipid A. ArnT modification of lipid A did not change its TLR4 agonist activity in J774 cells, but deleting arnT decreased resistance to killing by cationic antimicrob...