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      Emerging concepts in the pathogenesis of the Streptococcus pneumoniae: From nasopharyngeal colonizer to intracellular pathogen

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          Abstract

          Streptococcus pneumoniae (the pneumococcus) is a human respiratory tract pathogen and a major cause of morbidity and mortality globally. Although the pneumococcus is a commensal bacterium that colonizes the nasopharynx, it also causes lethal diseases such as meningitis, sepsis, and pneumonia, especially in immunocompromised patients, in the elderly, and in young children. Due to the acquisition of antibiotic resistance and the emergence of nonvaccine serotypes, the pneumococcus has been classified as one of the priority pathogens for which new antibacterials are urgently required by the World Health Organization, 2017. Understanding molecular mechanisms behind the pathogenesis of pneumococcal infections and bacterial interactions within the host is crucial to developing novel therapeutics. Previously considered to be an extracellular pathogen, it is becoming evident that pneumococci may also occasionally establish intracellular niches within the body to escape immune surveillance and spread within the host. Intracellular survival within host cells also enables pneumococci to resist many antibiotics. Within the host cell, the bacteria exist in unique vacuoles, thereby avoiding degradation by the acidic lysosomes, and modulate the expression of its virulence genes to adapt to the intracellular environment. To invade and survive intracellularly, the pneumococcus utilizes a combination of virulence factors such as pneumolysin (PLY), pneumococcal surface protein A (PspA), pneumococcal adhesion and virulence protein B (PavB), the pilus‐1 adhesin RrgA, pyruvate oxidase (SpxB), and metalloprotease (ZmpB). In this review, we discuss recent findings showing the intracellular persistence of Streptococcus pneumoniae and its underlying mechanisms.

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          Most cited references51

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          Concern that a highly pathogenic virus might cause the next influenza pandemic has spurred recent research into influenza and its complications. Bacterial superinfection in the lungs of people suffering from influenza is a key element that promotes severe disease and mortality. This co-pathogenesis is characterized by complex interactions between co-infecting pathogens and the host, leading to the disruption of physical barriers, dysregulation of immune responses and delays in a return to homeostasis. The net effect of this cascade can be the outgrowth of the pathogens, immune-mediated pathology and increased morbidity. In this Review, advances in our understanding of the underlying mechanisms are discussed, and the key questions that will drive the field forwards are articulated.
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              Cardiac complications in patients with community-acquired pneumonia: incidence, timing, risk factors, and association with short-term mortality.

              Community-acquired pneumonia (CAP) affects >5 million adults each year in the United States. Although incident cardiac complications occur in patients with community-acquired pneumonia, their incidence, timing, risk factors, and associations with short-term mortality are not well understood. A total of 1343 inpatients and 944 outpatients with community-acquired pneumonia were followed up prospectively for 30 days after presentation. Incident cardiac complications (new or worsening heart failure, new or worsening arrhythmias, or myocardial infarction) were diagnosed in 358 inpatients (26.7%) and 20 outpatients (2.1%). Although most events (89.1% in inpatients, 75% in outpatients) were diagnosed within the first week, more than half of them were recognized in the first 24 hours. Factors associated with their diagnosis included older age (odds ratio [OR]=1.03; 95% confidence interval [CI], 1.02-1.04), nursing home residence (OR, 1.8; 95% CI, 1.2-2.9), history of heart failure (OR, 4.3; 95% CI, 3.0-6.3), prior cardiac arrhythmias (OR, 1.8; 95% CI, 1.2-2.7), previously diagnosed coronary artery disease (OR, 1.5; 95% CI, 1.04-2.0), arterial hypertension (OR, 1.5; 95% CI, 1.1-2.1), respiratory rate ≥30 breaths per minute (OR, 1.6; 95% CI, 1.1-2.3), blood pH <7.35 (OR, 3.2; 95% CI, 1.8-5.7), blood urea nitrogen ≥30 mg/dL (OR, 1.5; 95% CI, 1.1-2.2), serum sodium <130 mmol/L (OR, 1.8; 95% CI, 1.02-3.1), hematocrit <30% (OR, 2.0; 95% CI, 1.3-3.2), pleural effusion on presenting chest x-ray (OR, 1.6; 95% CI, 1.1-2.4), and inpatient care (OR, 4.8; 95% CI, 2.8-8.3). Incident cardiac complications were associated with increased risk of death at 30 days after adjustment for baseline Pneumonia Severity Index score (OR, 1.6; 95% CI, 1.04-2.5). Incident cardiac complications are common in patients with community-acquired pneumonia and are associated with increased short-term mortality. Older age, nursing home residence, preexisting cardiovascular disease, and pneumonia severity are associated with their occurrence. Further studies are required to test risk stratification and prevention and treatment strategies for cardiac complications in this population.
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                Author and article information

                Contributors
                birgitta.henriques@ki.se
                staffan.normark@ki.se
                Journal
                Cell Microbiol
                Cell. Microbiol
                10.1111/(ISSN)1462-5822
                CMI
                Cellular Microbiology
                John Wiley and Sons Inc. (Hoboken )
                1462-5814
                1462-5822
                17 July 2019
                November 2019
                : 21
                : 11 , Two Decades Of Cellular Microbiology: A Tribute To Philippe Sansonetti ( doiID: 10.1111/cmi.v21.11 )
                : e13077
                Affiliations
                [ 1 ] Department of Microbiology, Tumor and Cell Biology Karolinska Institutet Stockholm Sweden
                [ 2 ] Clinical Microbiology Karolinska University Hospital Stockholm Sweden
                [ 3 ] Lee Kong Chian School of Medicine (LKC) and Singapore Centre on Environmental Life Sciences Engineering (SCELSE) Nanyang Technological University Singapore
                Author notes
                [*] [* ] Correspondence

                Prof. Birgitta Henriques‐Normark, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

                Email: birgitta.henriques@ 123456ki.se

                Prof. Staffan Normark, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

                Email: staffan.normark@ 123456ki.se

                Author information
                https://orcid.org/0000-0002-4381-5037
                https://orcid.org/0000-0002-5429-4759
                Article
                CMI13077 CMI-19-0057.R1
                10.1111/cmi.13077
                6899785
                31251447
                48434a8e-46dd-4f93-8dfd-98c3bd7ae902
                © 2019 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 March 2019
                : 17 June 2019
                : 21 June 2019
                Page count
                Figures: 1, Tables: 1, Pages: 10, Words: 4105
                Funding
                Funded by: The Knut and Alice Wallenberg Foundation , open-funder-registry 10.13039/501100004063;
                Funded by: The Swedish Research Council , open-funder-registry 10.13039/501100004359;
                Funded by: Stockholm County Council , open-funder-registry 10.13039/501100004348;
                Funded by: the Swedish Foundation for Strategic Research (SSF)
                Categories
                Special Issue ‐ Review
                Special Issue ‐ Reviews
                Custom metadata
                2.0
                November 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.2 mode:remove_FC converted:05.12.2019

                Microbiology & Virology
                immunity,intracellular survival,pathogenesis,persistence,pneumococci,streptococcus pneumoniae

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