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Clinical Microbiology Reviews Oct 2008Streptococcus pneumoniae is a colonizer of human nasopharynx, but it is also an important pathogen responsible for high morbidity, high mortality, numerous disabilities,... (Review)
Review
Streptococcus pneumoniae is a colonizer of human nasopharynx, but it is also an important pathogen responsible for high morbidity, high mortality, numerous disabilities, and high health costs throughout the world. Major diseases caused by S. pneumoniae are otitis media, pneumonia, sepsis, and meningitis. Despite the availability of antibiotics and vaccines, pneumococcal infections still have high mortality rates, especially in risk groups. For this reason, there is an exceptionally extensive research effort worldwide to better understand the diseases caused by the pneumococcus, with the aim of developing improved therapeutics and vaccines. Animal experimentation is an essential tool to study the pathogenesis of infectious diseases and test novel drugs and vaccines. This article reviews both historical and innovative laboratory pneumococcal animal models that have vastly added to knowledge of (i) mechanisms of infection, pathogenesis, and immunity; (ii) efficacies of antimicrobials; and (iii) screening of vaccine candidates. A comprehensive description of the techniques applied to induce disease is provided, the advantages and limitations of mouse, rat, and rabbit models used to mimic pneumonia, sepsis, and meningitis are discussed, and a section on otitis media models is also included. The choice of appropriate animal models for in vivo studies is a key element for improved understanding of pneumococcal disease.
Topics: Animals; Humans; Mice; Models, Animal; Pneumococcal Infections; Rabbits; Rats; Streptococcus pneumoniae
PubMed: 18854486
DOI: 10.1128/CMR.00012-08 -
Frontiers in Immunology 2019One host defense function of C-reactive protein (CRP) is to protect against infection as shown by experiments employing murine models of pneumococcal infection. The... (Review)
Review
One host defense function of C-reactive protein (CRP) is to protect against infection as shown by experiments employing murine models of pneumococcal infection. The protective effect of CRP is due to reduction in bacteremia. There is a distinct relationship between the structure of CRP and its anti-pneumococcal function. CRP is functional in both native and non-native pentameric structural conformations. In the native conformation, CRP binds to pneumococci through the phosphocholine molecules present on the C-polysaccharide of the pneumococcus and the anti-pneumococcal function probably involves the known ability of ligand-complexed CRP to activate the complement system. In the native structure-function relationship, CRP is protective only when given to mice within a few hours of the administration of pneumococci. The non-native pentameric conformation of CRP is created when CRP is exposed to conditions mimicking inflammatory microenvironments, such as acidic pH and redox conditions. In the non-native conformation, CRP binds to immobilized complement inhibitor factor H in addition to being able to bind to phosphocholine. Recent data using CRP mutants suggest that the factor H-binding function of non-native CRP is beneficial: in the non-native structure-function relationship, CRP can be given to mice any time after the administration of pneumococci irrespective of whether the pneumococci became complement-resistant or not. In conclusion, while native CRP is protective only against early stage infection, non-native CRP is protective against both early stage and late stage infections. Because non-native CRP displays phosphocholine-independent anti-pneumococcal activity, it is quite possible that CRP functions as a general anti-bacterial molecule.
Topics: Animals; Bacterial Infections; C-Reactive Protein; Host-Pathogen Interactions; Humans; Phosphorylcholine; Pneumococcal Infections; Protein Binding; Streptococcus pneumoniae; Structure-Activity Relationship
PubMed: 30863393
DOI: 10.3389/fimmu.2019.00166 -
Respirology (Carlton, Vic.) May 2011The incidence of pleural infection continues to rise worldwide. Identifying the causative organism(s) is important to guide antimicrobial therapy. The bacteriology of... (Review)
Review
The incidence of pleural infection continues to rise worldwide. Identifying the causative organism(s) is important to guide antimicrobial therapy. The bacteriology of pleural infection is complex and has changed over time. Recent data suggest that the bacterial causes of empyema are significantly different between adult and paediatric patients, between community-acquired and nosocomial empyemas and can vary among geographical regions of the world. Since the introduction of pneumococcal vaccines, a change has been observed in the distribution of the serotypes of Streptococcus pneumoniae in empyema. These observations have implications on therapy and vaccine strategies. Clinicians need to be aware of the local bacteriology of empyema in order to guide antibiotic treatment.
Topics: Bacterial Infections; Community-Acquired Infections; Cross Infection; Empyema, Pleural; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Serotyping
PubMed: 21382129
DOI: 10.1111/j.1440-1843.2011.01964.x -
Microbiology Spectrum Jun 2022The nasopharyngeal commensal Streptococcus pneumoniae can become invasive and cause metastatic infection. This requires the pneumococcus to have the ability to adapt,...
The nasopharyngeal commensal Streptococcus pneumoniae can become invasive and cause metastatic infection. This requires the pneumococcus to have the ability to adapt, grow, and reside in diverse host environments. Therefore, we studied whether the likelihood of severe disease manifestations was related to pneumococcal growth kinetics. For 383 S. pneumoniae blood isolates and 25 experimental mutants, we observed highly reproducible growth curves in nutrient-rich medium. The derived growth features were lag time, maximum growth rate, maximum density, and stationary-phase time before lysis. First, the pathogenicity of each growth feature was probed by comparing isolates from patients with and without marked preexisting comorbidity. Then, growth features were related to the propensity of causing severe manifestations of invasive pneumococcal disease (IPD). A high maximum bacterial density was the most pronounced pathogenic growth feature, which was also an independent predictor of 30-day mortality ( = 0.03). Serotypes with an epidemiologically higher propensity for causing meningitis displayed a relatively high maximum density ( < 0.005) and a short stationary phase ( < 0.005). Correspondingly, isolates from patients diagnosed with meningitis showed an especially high maximum density and short stationary phase compared to isolates from the same serotype that had caused uncomplicated bacteremic pneumonia. In contrast, empyema-associated strains were characterized by a relatively long lag phase ( < 0.0005), and slower growth ( < 0.005). The course and dissemination of IPD may partly be attributable to the pneumococcal growth features involved. If confirmed, we should tailor the prevention and treatment strategies for the different infection sites that can complicate IPD. Streptococcus pneumoniae is a leading infectious cause of deaths worldwide. To understand the course and outcome of pneumococcal infection, most research has focused on the host and its response to contain bacterial growth. However, bacterial epidemiology suggest that certain pneumococcal serotypes are particularly prone to causing complicated infections. Therefore, we took the bacterial point of view, simply examining growth features for hundreds of pneumococcal blood isolates. Their growth curves were very reproducible. Certain poles of pneumococcal growth features were indeed associated with specific clinical manifestations like meningitis or pleural empyema. This indicates that bacterial growth style potentially affects the progression of infection. Further research on bacterial growth and adaptation to different host environments may therefore provide key insight into pathogenesis of complicated invasive disease. Such knowledge could lead to more tailored vaccine targets or therapeutic approaches to reduce the million deaths that are caused by pneumococcal disease every year.
Topics: Humans; Infant; Meningitis; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Serotyping; Streptococcus pneumoniae
PubMed: 35678554
DOI: 10.1128/spectrum.00050-22 -
MBio May 2016Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The...
Streptococcus pneumoniae remains an important human pathogen. For more than 100 years, there have been vaccine efforts to prevent pneumococcal infection. The pneumococcal conjugate vaccines have significantly reduced invasive disease. However, these vaccines have changed pneumococcal ecology within the human nasopharynx. We suggest that elimination of the pneumococcus from the human nasopharynx can have consequences that should be considered as the next generation of pneumococcal vaccines is developed.
Topics: Carrier State; Humans; Infant; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 27222469
DOI: 10.1128/mBio.00545-16 -
Microbial Genomics Jul 2023is a major human pathogen and can cause a range of conditions from asymptomatic colonization to invasive pneumococcal disease (IPD). The epidemiology and distribution...
is a major human pathogen and can cause a range of conditions from asymptomatic colonization to invasive pneumococcal disease (IPD). The epidemiology and distribution of IPD-causing serotypes in Australia has undergone large changes following the introduction of the 7-valent pneumococcal conjugate vaccine (PCV) in 2005 and the 13-valent PCV in 2011. In this study, to provide a contemporary understanding of the IPD causing population in Victoria, Australia, we aimed to examine the population structure and prevalence of antimicrobial resistance using whole-genome sequencing and comprehensive antimicrobial susceptibility data of 1288 isolates collected between 2018 and 2022. We observed high diversity among the isolates with 52 serotypes, 203 sequence types (STs) and 70 Global Pneumococcal Sequencing Project Clusters (GPSCs) identified. Serotypes contained in the 13v-PCV represented 35.3 % (=405) of isolates. Antimicrobial resistance (AMR) to at least one antibiotic was identified in 23.8 % (=358) of isolates with penicillin resistance the most prevalent (20.3 %, =261 using meningitis breakpoints and 5.1 % =65 using oral breakpoints). Of the AMR isolates, 28 % (=101) were multidrug resistant (MDR) (resistant to three or more drug classes). Vaccination status of cases was determined for a subset of isolates with 34 cases classified as vaccine failure events (fully vaccinated IPD cases of vaccine serotype). However, no phylogenetic association with failure events was observed. Within the highly diverse IPD population, we identified six high-risk sub-populations of public health concern characterized by high prevalence, high rates of AMR and MDR, or serotype inclusion in vaccines. High-risk serotypes included serotypes 3, 19F, 19A, 14, 11A, 15A and serofamily 23. In addition, we present our data validating seroBA for serotyping to facilitate ISO-accreditation of this test in routine use in a public health reference laboratory and have made this data set available. This study provides insights into the population dynamics, highlights non-vaccine serotypes of concern that are highly resistant, and provides a genomic framework for the ongoing surveillance of IPD in Australia which can inform next-generation IPD prevention strategies.
Topics: Humans; Streptococcus pneumoniae; Serogroup; Victoria; Pneumococcal Infections; Drug Resistance, Microbial; Anti-Bacterial Agents
PubMed: 37471116
DOI: 10.1099/mgen.0.001070 -
Mechanistic Insights into the Impact of Air Pollution on Pneumococcal Pathogenesis and Transmission.American Journal of Respiratory and... Nov 2022(the pneumococcus) is the leading cause of pneumonia and bacterial meningitis. A number of recent studies indicate an association between the incidence of pneumococcal... (Review)
Review
(the pneumococcus) is the leading cause of pneumonia and bacterial meningitis. A number of recent studies indicate an association between the incidence of pneumococcal disease and exposure to air pollution. Although the epidemiological evidence is substantial, the underlying mechanisms by which the various components of air pollution (particulate matter and gases such as NO and SO) can increase susceptibility to pneumococcal infection are less well understood. In this review, we summarize the various effects air pollution components have on pneumococcal pathogenesis and transmission; exposure to air pollution can enhance host susceptibility to pneumococcal colonization by impairing the mucociliary activity of the airway mucosa, reducing the function and production of key antimicrobial peptides, and upregulating an important pneumococcal adherence factor on respiratory epithelial cells. Air pollutant exposure can also impair the phagocytic killing ability of macrophages, permitting increased replication of . In addition, particulate matter has been shown to activate various extra- and intracellular receptors of airway epithelial cells, which may lead to increased proinflammatory cytokine production. This increases recruitment of innate immune cells, including macrophages and neutrophils. The inflammatory response that ensues may result in significant tissue damage, thereby increasing susceptibility to invasive disease, because it allows access to the underlying tissues and blood. This review provides an in-depth understanding of the interaction between air pollution and the pneumococcus, which has the potential to aid the development of novel treatments or alternative strategies to prevent disease, especially in areas with high concentrations of air pollution.
Topics: Humans; Streptococcus pneumoniae; Air Pollution; Air Pollutants; Particulate Matter; Pneumonia; Pneumococcal Infections
PubMed: 35649181
DOI: 10.1164/rccm.202112-2668TR -
Clinical Infectious Diseases : An... May 2011Streptococcus pneumoniae is both an aggressive pathogen and a normal part of the human respiratory microbiome. Clinicians and microbiologists have struggled to develop... (Review)
Review
Streptococcus pneumoniae is both an aggressive pathogen and a normal part of the human respiratory microbiome. Clinicians and microbiologists have struggled to develop tests that can identify pneumococcal respiratory infection and accurately distinguish colonization from invasive disease. Molecular methods hold the promise of an improved ability to rapidly detect microorganisms in respiratory secretions and to make an accurate diagnosis; however, interpretation of diagnostic testing for S. pneumoniae remains problematic. Molecular assays, such as those targeting the pneumolysin gene, may cross-react with other streptococcal species, confounding detection and quantification. Assays that target the autolysin gene appear to be more specific. Even when accurately identified, however, the significance of S. pneumoniae DNA detected in clinical samples is difficult to determine. Here we will discuss the challenges faced in the interpretation of molecular testing for S. pneumoniae, and some strategies that might be used to improve our ability to diagnose pneumococcal respiratory infection.
Topics: Bacteriological Techniques; Carrier State; Humans; Pneumococcal Infections; Sensitivity and Specificity; Streptococcus pneumoniae
PubMed: 21460292
DOI: 10.1093/cid/cir048 -
Vaccine Aug 2022The risk of developing pneumococcal infections increases with certain chronic conditions and in immunocompromised patients. We aimed to monitor pneumococcal vaccination... (Observational Study)
Observational Study
INTRODUCTION
The risk of developing pneumococcal infections increases with certain chronic conditions and in immunocompromised patients. We aimed to monitor pneumococcal vaccination coverage in at-risk patients and to examine factors associated with pneumococcal vaccination in France.
MATERIAL AND METHODS
In this annual cross-sectional study, at-risk patients were extracted between 2014 and 2018 from the National Health Insurance's (NHI) General scheme's claims database with their vaccine reimbursements. Descriptive analyses and a logistic model were performed to assess the influence of healthcare use and medical and demographic factors on pneumococcal vaccination.
RESULTS AND DISCUSSION
In 2018, 4.5% of 4,045,021 at-risk adults were up to date with their pneumococcal vaccination. During the study period, the number of patients with chronic medical conditions (86% of 4,045,021) increased by 10.1%, but vaccination coverage decreased from 12.9% to 2.9%. The population with immunocompromised status (14% of 4,045,021) increased by 16.2% and vaccination coverage from 10.3% to 18.8%. Influenza vaccination coverage was much higher and stable (around 45.0%). Factors associated with pneumococcal vaccination were: immunocompromised status vs. having a chronic medical condition (odds ratio [OR] 4.72), influenza vaccination (OR 2.36-3.42), hepatitis B vaccination (OR 2.82), DTPolio vaccination (OR 1.52), ≥5 specialist physicians' visits (OR 1.17), and age above 74 (OR 1.12). Pneumococcal vaccine dispensing was extremely low (median of 9per GP,1per specialist over 9 years) despite frequent healthcare visits.
CONCLUSION
Pneumococcal and influenza vaccination coverage of adults at risk of pneumococcal disease fell well below public health expectations. Invitations for pneumococcal vaccination should be sent by the NHI to high-risk patients. Patient management protocols should include pneumococcal vaccination. Patients with multiple comorbidities are a high-priority population given the large potential health gains offered by pneumococcal vaccination. Commitment of both scientific societies and health authorities is urgently needed to increase vaccination coverage in at-risk populations.
Topics: Adult; Cross-Sectional Studies; Humans; Influenza Vaccines; Influenza, Human; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccination; Vaccination Coverage
PubMed: 35811205
DOI: 10.1016/j.vaccine.2022.06.071 -
Microbiology Spectrum Jun 2023Pneumococcal pneumonia remains a WHO high-priority disease despite multivalent conjugate vaccines administered in clinical practice worldwide. A protein-based,...
Pneumococcal pneumonia remains a WHO high-priority disease despite multivalent conjugate vaccines administered in clinical practice worldwide. A protein-based, serotype-independent vaccine has long-promised comprehensive coverage of most clinical isolates of the pneumococcus. Along with numerous pneumococcal surface protein immunogens, the pneumococcal serine-rich repeat protein (PsrP) has been investigated as a potential vaccine target due to its surface exposure and functions toward bacterial virulence and lung infection. Three critical criteria for its vaccine potential - the clinical prevalence, serotype distribution, and sequence homology of PsrP - have yet to be well characterized. Here, we used genomes of 13,454 clinically isolated pneumococci from the Global Pneumococcal Sequencing project to investigate PsrP presence among isolates, distribution among serotypes, and interrogate its homology as a protein across species. These isolates represent all age groups, countries worldwide, and types of pneumococcal infection. We found PsrP present in at least 50% of all isolates across all determined serotypes and nontypeable (NT) clinical isolates. Using a combination of peptide matching and HMM profiles built on full-length and individual PsrP domains, we identified novel variants that expand PsrP diversity and prevalence. We also observed sequence variability in its basic region (BR) between isolates and serotypes. PsrP has a strong vaccine potential due to its breadth of coverage, especially in nonvaccine serotypes (NVTs) when exploiting its regions of conservation in vaccine design. An updated outlook on PsrP prevalence and serotype distribution sheds new light on the comprehensiveness of a PsrP-based protein vaccine. The protein is present in all vaccine serotypes and highly present in the next wave of potentially disease-causing serotypes not included in the current multivalent conjugate vaccines. Furthermore, PsrP is strongly correlated with clinical isolates harboring pneumococcal disease as opposed to pneumococcal carriage. PsrP is also highly present in strains and serotypes from Africa, where the need for a protein-based vaccine is the greatest, giving new reasoning to pursue PsrP as a protein vaccine.
Topics: Humans; Streptococcus pneumoniae; Vaccines, Conjugate; Prevalence; Pneumococcal Infections; Pneumococcal Vaccines
PubMed: 36995217
DOI: 10.1128/spectrum.03252-22