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      Exposure of a 23F Serotype Strain of Streptococcus pneumoniae to Cigarette Smoke Condensate Is Associated with Selective Upregulation of Genes Encoding the Two-Component Regulatory System 11 (TCS11)

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          Abstract

          Alterations in whole genome expression profiles following exposure of the pneumococcus (strain 172, serotype 23F) to cigarette smoke condensate (160  μ g/mL) for 15 and 60 min have been determined using the TIGR4 DNA microarray chip. Exposure to CSC resulted in the significant ( P < 0.014–0.0006) upregulation of the genes encoding the two-component regulatory system 11 (TCS11), consisting of the sensor kinase, hk11, and its cognate response regulator, rr11, in the setting of increased biofilm formation. These effects of cigarette smoke on the pneumococcus may contribute to colonization of the airways by this microbial pathogen.

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          Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team.

          Approximately half of otherwise healthy adults with invasive pneumococcal disease are cigarette smokers. We conducted a population-based case-control study to assess the importance of cigarette smoking and other factors as risk factors for pneumococcal infections. We identified immunocompetent patients who were 18 to 64 years old and who had invasive pneumococcal disease (as defined by the isolation of Streptococcus pneumoniae from a normally sterile site) by active surveillance of laboratories in metropolitan Atlanta, Baltimore, and Toronto. Telephone interviews were conducted with 228 patients and 301 control subjects who were reached by random-digit dialing. Fifty-eight percent of the patients and 24 percent of the control subjects were current smokers. Invasive pneumococcal disease was associated with cigarette smoking (odds ratio, 4.1; 95 percent confidence interval, 2.4 to 7.3) and with passive smoking among nonsmokers (odds ratio, 2.5; 95 percent confidence interval, 1.2 to 5.1) after adjustment by logistic-regression analysis for age, study site, and independent risk factors such as male sex, black race, chronic illness, low level of education, and living with young children who were in day care. There were dose-response relations for the current number of cigarettes smoked per day, pack-years of smoking, and time since quitting. The adjusted population attributable risk was 51 percent for cigarette smoking, 17 percent for passive smoking, and 14 percent for chronic illness. Cigarette smoking is the strongest independent risk factor for invasive pneumococcal disease among immunocompetent, nonelderly adults. Because of the high prevalence of smoking and the large population attributable risk, programs to reduce both smoking and exposure to environmental tobacco smoke have the potential to reduce the incidence of pneumococcal disease.
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            Human Pathogens Abundant in the Bacterial Metagenome of Cigarettes

            Background Many studies have evaluated chemical, heavy metal, and other abiotic substances present in cigarettes and their roles in the development of lung cancer and other diseases, yet no studies have comprehensively evaluated bacterial diversity of cigarettes and the possible impacts of these microbes on respiratory illnesses in smokers and exposed nonsmokers. Objectives The goal of this study was to explore the bacterial metagenomes of commercially available cigarettes. Methods A 16S rRNA-based taxonomic microarray and cloning and sequencing were used to evaluate total bacterial diversity of four brands of cigarettes. Normalized microarray data were compared using principal component analysis and hierarchical cluster analysis to evaluate potential differences in microbial diversity across cigarette brands. Results Fifteen different classes of bacteria and a broad range of potentially pathogenic organisms were detected in all cigarette samples. Most notably, we detected Acinetobacter, Bacillus, Burkholderia, Clostridium, Klebsiella, Pseudomonas aeruginosa, and Serratia in ≥ 90% of all cigarette samples. Other pathogenic bacteria detected included Campylobacter, Enterococcus, Proteus, and Staphylococcus. No significant variability in bacterial diversity was observed across the four different cigarette brands. Conclusions Previous studies have shown that smoking is associated with colonization by pathogenic bacteria and an increased risk of lung infections. However, this is the first study to show that cigarettes themselves could be the direct source of exposure to a wide array of potentially pathogenic microbes among smokers and other people exposed to secondhand smoke. The overall public health implications of these findings are unclear at this time, and future studies are necessary to determine whether bacteria in cigarettes could play important roles in the development of both infectious and chronic respiratory diseases.
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              A genomic analysis of two-component signal transduction in Streptococcus pneumoniae.

              A genomics-based approach was used to identify the entire gene complement of putative two-component signal transduction systems (TCSTSs) in Streptococcus pneumoniae. A total of 14 open reading frames (ORFs) were identified as putative response regulators, 13 of which were adjacent to genes encoding probable histidine kinases. Both the histidine kinase and response regulator proteins were categorized into subfamilies on the basis of phylogeny. Through a systematic programme of mutagenesis, the importance of each novel TCSTS was determined with respect to viability and pathogenicity. One TCSTS was identified that was essential for the growth of S. pneumoniaeThis locus was highly homologous to the yycFG gene pair encoding the essential response regulator/histidine kinase proteins identified in Bacillus subtilis and Staphylococcus aureus. Separate deletions of eight other loci led in each case to a dramatic attenuation of growth in a mouse respiratory tract infection model, suggesting that these signal transduction systems are important for the in vivo adaptation and pathogenesis of S. pneumoniae. The identification of conserved TCSTSs important for both pathogenicity and viability in a Gram-positive pathogen highlights the potential of two-component signal transduction as a multicomponent target for antibacterial drug discovery.
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                Author and article information

                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi Publishing Corporation
                2314-6133
                2314-6141
                2014
                11 June 2014
                : 2014
                : 976347
                Affiliations
                1Medical Research Council Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Pretoria 0001, South Africa
                2Tshwane Academic Division of the National Health Laboratory Service, 1 Modderfontein Road, Sandringham, Johannesburg 2192, South Africa
                3Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK
                4Institute for Microbiology and Infection, School of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK
                5Divisions of Haematology and Pulmonology, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand and Charlotte Maxeke Johannesburg Academic Hospital, Private Bag 3,WITS, Johannesburg 2050, South Africa
                Author notes

                Academic Editor: Angel Cataldi

                Author information
                http://orcid.org/0000-0001-9227-6124
                Article
                10.1155/2014/976347
                4071851
                740d95e7-fa32-4b46-9cc7-8807b59f10a3
                Copyright © 2014 Riana Cockeran et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 February 2014
                : 15 May 2014
                : 21 May 2014
                Funding
                Funded by: http://dx.doi.org/10.13039/501100001321 National Research Foundation
                Funded by: http://dx.doi.org/10.13039/501100001322 South African Medical Research Council
                Categories
                Research Article

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