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Background. Pneumococcal serotypes are represented by a varying number of clonal lineages with different genetic contents, potentially affecting invasiveness. However, genetic variation within the same genetic lineage may be larger than anticipated. Methods. A total of 715 invasive and carriage isolates from children in the same region and during the same period were compared using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Bacterial genome sequencing, functional assays, and in vivo virulence mice studies were performed. Results. Clonal types of the same serotype but also intraclonal variants within clonal complexes (CCs) showed differences in invasive-disease potential. CC138, a common CC, was divided into several PFGE patterns, partly explained by number, location, and type of temperate bacteriophages. Whole-genome sequencing of 4 CC138 isolates representing PFGE clones with different invasive-disease potentials revealed intraclonal sequence variations of the virulence-associated proteins pneumococcal surface protein A (PspA) and pneumococcal choline-binding protein C (PspC). A carrier isolate lacking PcpA exhibited decreased virulence in mice, and there was a differential binding of human factor H, depending on invasiveness. Conclusions. Pneumococcal clonal types but also intraclonal variants exhibited different invasive-disease potentials in children. Intraclonal variants, reflecting different prophage contents, showed differences in major surface antigens. This suggests ongoing immune selection, such as that due to PspC-mediated complement resistance through varied human factor H binding, that may affect invasiveness in children.

Siderocalin is a secreted protein that binds to siderophores to prevent bacterial iron acquisition. While it has been shown to inhibit the growth of Mycobacterium tuberculosis (M.tb) in extracellular cultures, its effect on this pathogen within macrophages is not clear. Here, we show that siderocalin expression is upregulated following M.tb infection of mouse macrophage cell lines and primary murine alveolar macrophages. Furthermore, siderocalin added exogenously as a recombinant protein or overexpressed in the RAW264.7 macrophage cell line inhibited the intracellular growth of the pathogen. A variant form of siderocalin, which is expressed only in the macrophage cytosol, inhibited intracellular M.tb growth as effectively as the normal, secreted form, an observation that provides mechanistic insight into how siderocalin might influence iron acquisition by the bacteria in the phagosome. Our findings are consistent with an important role for siderocalin in protection against M.tb infection and suggest that exogenously administered siderocalin may have therapeutic applications in tuberculosis.

Siderocalin is a secreted protein that binds to siderophores to prevent bacterial iron acquisition. While it has been shown to inhibit the growth of Mycobacterium tuberculosis (M.tb) in extracellular cultures, its effect on this pathogen within macrophages is not clear. Here, we show that siderocalin expression is upregulated following M.tb infection of mouse macrophage cell lines and primary murine alveolar macrophages. Furthermore, siderocalin added exogenously as a recombinant protein or overexpressed in the RAW264.7 macrophage cell line inhibited the intracellular growth of the pathogen. A variant form of siderocalin, which is expressed only in the macrophage cytosol, inhibited intracellular M.tb growth as effectively as the normal, secreted form, an observation that provides mechanistic insight into how siderocalin might influence iron acquisition by the bacteria in the phagosome. Our findings are consistent with an important role for siderocalin in protection against M.tb infection and suggest that exogenously administered siderocalin may have therapeutic applications in tuberculosis.

Tuberculosis (TB) remains the leading cause of death from a largely preventable and curable infectious disease, with an estimated 1.7 million deaths in 2006. Global prospects for TB control are challenged by the emergence of drug-resistant strains, especially those that are multidrug resistant (MDR) and extensively drug resistant (XDR).

BACKGROUND: The incidence and severity of invasive group A streptococcal infection demonstrate great variability over time, which at least, in part, seems to be related to group A streptococcal type distribution among the human population. METHODS: An enhanced surveillance study of invasive group A streptococcal infection (746 isolates) was performed in Sweden from April 2002 through December 2004. Noninvasive isolates from either the throat or skin (773 isolates) were collected in parallel for comparison. Clinical and epidemiological data were obtained from 88% of patients with invasive disease and were related to isolate characteristics, including T type, emm sequence type, and the presence of 9 superantigen genes, as well as pulsed-field gel electrophoresis pattern comparisons of selected isolates. RESULTS: The annual incidence was 3.0 cases per 100,000 population. Among the patients with invasive disease, 11% developed streptococcal toxic shock syndrome, and 9.5% developed necrotizing fasciitis. The overall case-fatality rate was 14.5%, and 39% of the patients with streptococcal toxic shock syndrome died (P<.001). The T3/13/B3264 cluster accounted for 33% of invasive and 25% of noninvasive isolates. Among this most prevalent type cluster, emm types 89 and 81 dominated. Combined results from pulsed-field gel electrophoresis, emm typing, and superantigen gene profiling identified subgroups within specific emm types that are significantly more prone to cause invasive disease than were other isolates of the same type. CONCLUSIONS: This study revealed a changing epidemiology of invasive group A streptococcal infection in Sweden, with emergence of new emm types that were previously not described. The results also suggest that some clones may be particularly prone to cause invasive disease.

Streptococcus pneumoniae, also known as the pneumococcus, is a human specific bacterium and causes infections like otitis media, sinusitis, pneumonia, sepsis and meningitis. However, these bacteria are also frequent colonizers of the nasopharynx of healthy individuals, especially children. The major virulence factor in pneumococci is the polysaccharide capsule, which protects against phagocytosis. The death of pneumococci releases high amounts of potent mediators of inflammation. The innate immune system constitutes the first line of host defense against microbial infections. Pattern recognition receptors such as the Toll-Like Receptors (TLRs) mediate innate immune responses upon recognition of bacterial components through adaptor molecules such as MyD88. The overarching goal of the present work was to understand underlying mechanisms in the microbe as well as in the host that contribute to the transition from a local commensal microbe-host interaction to a systemic infection, and the innate immune responses associated with both local microbial control and development of invasive disease. Clinical isolates from patients with invasive disease and from healthy children attending day-care centers were collected in the Stockholm area during 1997. The isolates were characterized using molecular fingerprinting methods such as Pulsed Field Gel Electrophoresis and Multi Locus Sequence Typing. Further, we characterized the virulence of these isolates in mouse infection models. By using wild type mice and mice deficient in the different TLRs and MyD88 we investigated the role of these molecules for resistance against pneumococcal infection. A novel technique using biophotonic real-time in vivo imaging has been applied to understand the infection process within living animals. We found that 40 % of the children attending day-care centers harbored pneumococci; 20 % of the isolates were non-susceptible to penicillin. We could observe cases of spread between children of pneumococ

Streptococcus pneumoniae, also known as the pneumococcus, is a human specific bacterium and causes infections like otitis media, sinusitis, pneumonia, sepsis and meningitis. However, these bacteria are also frequent colonizers of the nasopharynx of healthy individuals, especially children. The major virulence factor in pneumococci is the polysaccharide capsule, which protects against phagocytosis. The death of pneumococci releases high amounts of potent mediators of inflammation. The innate immune system constitutes the first line of host defense against microbial infections. Pattern recognition receptors such as the Toll-Like Receptors (TLRs) mediate innate immune responses upon recognition of bacterial components through adaptor molecules such as MyD88. The overarching goal of the present work was to understand underlying mechanisms in the microbe as well as in the host that contribute to the transition from a local commensal microbe-host interaction to a systemic infection, and the innate immune responses associated with both local microbial control and development of invasive disease. Clinical isolates from patients with invasive disease and from healthy children attending day-care centers were collected in the Stockholm area during 1997. The isolates were characterized using molecular fingerprinting methods such as Pulsed Field Gel Electrophoresis and Multi Locus Sequence Typing. Further, we characterized the virulence of these isolates in mouse infection models. By using wild type mice and mice deficient in the different TLRs and MyD88 we investigated the role of these molecules for resistance against pneumococcal infection. A novel technique using biophotonic real-time in vivo imaging has been applied to understand the infection process within living animals. We found that 40 % of the children attending day-care centers harbored pneumococci; 20 % of the isolates were non-susceptible to penicillin. We could observe cases of spread between children of pneumococ

Streptococcus pneumoniae, also known as the pneumococcus, is a human specific bacterium and causes infections like otitis media, sinusitis, pneumonia, sepsis and meningitis. However, these bacteria are also frequent colonizers of the nasopharynx of healthy individuals, especially children. The major virulence factor in pneumococci is the polysaccharide capsule, which protects against phagocytosis. The death of pneumococci releases high amounts of potent mediators of inflammation. The innate immune system constitutes the first line of host defense against microbial infections. Pattern recognition receptors such as the Toll-Like Receptors (TLRs) mediate innate immune responses upon recognition of bacterial components through adaptor molecules such as MyD88. The overarching goal of the present work was to understand underlying mechanisms in the microbe as well as in the host that contribute to the transition from a local commensal microbe-host interaction to a systemic infection, and the innate immune responses associated with both local microbial control and development of invasive disease. Clinical isolates from patients with invasive disease and from healthy children attending day-care centers were collected in the Stockholm area during 1997. The isolates were characterized using molecular fingerprinting methods such as Pulsed Field Gel Electrophoresis and Multi Locus Sequence Typing. Further, we characterized the virulence of these isolates in mouse infection models. By using wild type mice and mice deficient in the different TLRs and MyD88 we investigated the role of these molecules for resistance against pneumococcal infection. A novel technique using biophotonic real-time in vivo imaging has been applied to understand the infection process within living animals. We found that 40 % of the children attending day-care centers harbored pneumococci; 20 % of the isolates were non-susceptible to penicillin. We could observe cases of spread between children of pneumococ

Streptococcus pneumoniae, also known as the pneumococcus, is a human specific bacterium and causes infections like otitis media, sinusitis, pneumonia, sepsis and meningitis. However, these bacteria are also frequent colonizers of the nasopharynx of healthy individuals, especially children. The major virulence factor in pneumococci is the polysaccharide capsule, which protects against phagocytosis. The death of pneumococci releases high amounts of potent mediators of inflammation. The innate immune system constitutes the first line of host defense against microbial infections. Pattern recognition receptors such as the Toll-Like Receptors (TLRs) mediate innate immune responses upon recognition of bacterial components through adaptor molecules such as MyD88. The overarching goal of the present work was to understand underlying mechanisms in the microbe as well as in the host that contribute to the transition from a local commensal microbe-host interaction to a systemic infection, and the innate immune responses associated with both local microbial control and development of invasive disease. Clinical isolates from patients with invasive disease and from healthy children attending day-care centers were collected in the Stockholm area during 1997. The isolates were characterized using molecular fingerprinting methods such as Pulsed Field Gel Electrophoresis and Multi Locus Sequence Typing. Further, we characterized the virulence of these isolates in mouse infection models. By using wild type mice and mice deficient in the different TLRs and MyD88 we investigated the role of these molecules for resistance against pneumococcal infection. A novel technique using biophotonic real-time in vivo imaging has been applied to understand the infection process within living animals. We found that 40 % of the children attending day-care centers harbored pneumococci; 20 % of the isolates were non-susceptible to penicillin. We could observe cases of spread between children of pneumococ

Streptococcus pneumoniae, also known as the pneumococcus, is a human specific bacterium and causes infections like otitis media, sinusitis, pneumonia, sepsis and meningitis. However, these bacteria are also frequent colonizers of the nasopharynx of healthy individuals, especially children. The major virulence factor in pneumococci is the polysaccharide capsule, which protects against phagocytosis. The death of pneumococci releases high amounts of potent mediators of inflammation. The innate immune system constitutes the first line of host defense against microbial infections. Pattern recognition receptors such as the Toll-Like Receptors (TLRs) mediate innate immune responses upon recognition of bacterial components through adaptor molecules such as MyD88. The overarching goal of the present work was to understand underlying mechanisms in the microbe as well as in the host that contribute to the transition from a local commensal microbe-host interaction to a systemic infection, and the innate immune responses associated with both local microbial control and development of invasive disease. Clinical isolates from patients with invasive disease and from healthy children attending day-care centers were collected in the Stockholm area during 1997. The isolates were characterized using molecular fingerprinting methods such as Pulsed Field Gel Electrophoresis and Multi Locus Sequence Typing. Further, we characterized the virulence of these isolates in mouse infection models. By using wild type mice and mice deficient in the different TLRs and MyD88 we investigated the role of these molecules for resistance against pneumococcal infection. A novel technique using biophotonic real-time in vivo imaging has been applied to understand the infection process within living animals. We found that 40 % of the children attending day-care centers harbored pneumococci; 20 % of the isolates were non-susceptible to penicillin. We could observe cases of spread between children of pneumococ

How can small and medium sized enterprises (SMEs) stay competitive in the future when the challenge from low-cost countries is getting more and more severe? One possibility is to enter collaborative settings with other companies and in that way increase the supplier capabilities. But, in that case, which factors are most important when creating efficient supply networks? Technical foresights and roadmaps exemplify several issues that are important to develop to be successful in the future, such as to have an environmental consciousness for product and production. It is also important to create collaboration between suppliers as a mean to become more interesting as partners for systems integrators. This is a process for small and medium sized enterprises in their efforts to meet the increasing global competition. Collaborations between independent enterprises are however not easily created. Several factors will affect suppliers’ ability to create these collaborative networks and make them strong enough to enable competitive strength towards threats from actors on the global market. This article describes the most important success factors for these collaborative networks.

Streptococcus pneumoniae, also known as the pneumococcus, is a human specific bacterium and causes infections like otitis media, sinusitis, pneumonia, sepsis and meningitis. However, these bacteria are also frequent colonizers of the nasopharynx of healthy individuals, especially children. The major virulence factor in pneumococci is the polysaccharide capsule, which protects against phagocytosis. The death of pneumococci releases high amounts of potent mediators of inflammation. The innate immune system constitutes the first line of host defense against microbial infections. Pattern recognition receptors such as the Toll-Like Receptors (TLRs) mediate innate immune responses upon recognition of bacterial components through adaptor molecules such as MyD88. The overarching goal of the present work was to understand underlying mechanisms in the microbe as well as in the host that contribute to the transition from a local commensal microbe-host interaction to a systemic infection, and the innate immune responses associated with both local microbial control and development of invasive disease. Clinical isolates from patients with invasive disease and from healthy children attending day-care centers were collected in the Stockholm area during 1997. The isolates were characterized using molecular fingerprinting methods such as Pulsed Field Gel Electrophoresis and Multi Locus Sequence Typing. Further, we characterized the virulence of these isolates in mouse infection models. By using wild type mice and mice deficient in the different TLRs and MyD88 we investigated the role of these molecules for resistance against pneumococcal infection. A novel technique using biophotonic real-time in vivo imaging has been applied to understand the infection process within living animals. We found that 40 % of the children attending day-care centers harbored pneumococci; 20 % of the isolates were non-susceptible to penicillin. We could observe cases of spread between children of pneumococ

Streptococcus pneumoniae, also known as the pneumococcus, is a human specific bacterium and causes infections like otitis media, sinusitis, pneumonia, sepsis and meningitis. However, these bacteria are also frequent colonizers of the nasopharynx of healthy individuals, especially children. The major virulence factor in pneumococci is the polysaccharide capsule, which protects against phagocytosis. The death of pneumococci releases high amounts of potent mediators of inflammation. The innate immune system constitutes the first line of host defense against microbial infections. Pattern recognition receptors such as the Toll-Like Receptors (TLRs) mediate innate immune responses upon recognition of bacterial components through adaptor molecules such as MyD88. The overarching goal of the present work was to understand underlying mechanisms in the microbe as well as in the host that contribute to the transition from a local commensal microbe-host interaction to a systemic infection, and the innate immune responses associated with both local microbial control and development of invasive disease. Clinical isolates from patients with invasive disease and from healthy children attending day-care centers were collected in the Stockholm area during 1997. The isolates were characterized using molecular fingerprinting methods such as Pulsed Field Gel Electrophoresis and Multi Locus Sequence Typing. Further, we characterized the virulence of these isolates in mouse infection models. By using wild type mice and mice deficient in the different TLRs and MyD88 we investigated the role of these molecules for resistance against pneumococcal infection. A novel technique using biophotonic real-time in vivo imaging has been applied to understand the infection process within living animals. We found that 40 % of the children attending day-care centers harbored pneumococci; 20 % of the isolates were non-susceptible to penicillin. We could observe cases of spread between children of pneumococ

Streptococcus pneumoniae, also known as the pneumococcus, is a human specific bacterium and causes infections like otitis media, sinusitis, pneumonia, sepsis and meningitis. However, these bacteria are also frequent colonizers of the nasopharynx of healthy individuals, especially children. The major virulence factor in pneumococci is the polysaccharide capsule, which protects against phagocytosis. The death of pneumococci releases high amounts of potent mediators of inflammation. The innate immune system constitutes the first line of host defense against microbial infections. Pattern recognition receptors such as the Toll-Like Receptors (TLRs) mediate innate immune responses upon recognition of bacterial components through adaptor molecules such as MyD88. The overarching goal of the present work was to understand underlying mechanisms in the microbe as well as in the host that contribute to the transition from a local commensal microbe-host interaction to a systemic infection, and the innate immune responses associated with both local microbial control and development of invasive disease. Clinical isolates from patients with invasive disease and from healthy children attending day-care centers were collected in the Stockholm area during 1997. The isolates were characterized using molecular fingerprinting methods such as Pulsed Field Gel Electrophoresis and Multi Locus Sequence Typing. Further, we characterized the virulence of these isolates in mouse infection models. By using wild type mice and mice deficient in the different TLRs and MyD88 we investigated the role of these molecules for resistance against pneumococcal infection. A novel technique using biophotonic real-time in vivo imaging has been applied to understand the infection process within living animals. We found that 40 % of the children attending day-care centers harbored pneumococci; 20 % of the isolates were non-susceptible to penicillin. We could observe cases of spread between children of pneumococ

Background: Although tuberculosis (TB) incidence has been decreasing in the European Union/European Economic Area (EU/EEA) in the last decades, specific subgroups of the population, such as migrants, remain at high risk of TB. This study is based on the report ‘Key Infectious Diseases in Migrant Populations in the EU/EEA’ commissioned by The European Centre for Disease Prevention and Control. Methods: We collected, critically appraised and summarized the available evidence on the TB burden in migrants in the EU/EEA. Data were collected through: (i) a comprehensive literature review; (ii) analysis of data from The European Surveillance System (TESSy) and (iii) evidence provided by TB experts during an infectious disease workshop in 2012. Results: In 2010, of the 73 996 TB cases notified in the EU/EEA, 25% were of foreign origin. The overall decrease of TB cases observed in recent years has not been reflected in migrant populations. Foreign-born people with TB exhibit different socioeconomic and clinical characteristics than native sufferers. Conclusion: This is one of the first studies to use multiple data sources, including the largest available European database on infectious disease notifications, to assess the burden and provide a comprehensive description and analysis of specific TB features in migrants in the EU/EEA. Strengthened information about health determinants and factors for migrants’ vulnerability is needed to plan, implement and evaluate targeted TB care and control interventions for migrants in the EU/EEA.