scholarly journals Minimally-invasive nasal sampling in children offers accurate pneumococcal colonization detection

2019 ◽  
Author(s):  
Elissavet Nikolaou ◽  
Annie Blizard ◽  
Sherin Pojar ◽  
Elena Mitsi ◽  
Esther L. German ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Minimally Invasive ◽  
Invasive Disease ◽  
Detection Sensitivity ◽  
Respiratory Pathogens ◽  
Nasopharyngeal Colonization ◽  
Filter Strips ◽  
Fluid Filter ◽  
Pneumococcal Colonization

AbstractNasopharyngeal colonization of potential respiratory pathogens such as Streptococcus pneumoniae is the major source of transmission and precursor of invasive disease. Swabbing deeply the nasopharynx, which is currently recommended by WHO, provides accurate pneumococcal detection but is unpleasant. We showed that nasal lining fluid filter strips offer equal detection sensitivity.

scholarly journals The Ami-AliA/AliB Permease of Streptococcus pneumoniae Is Involved in Nasopharyngeal Colonization but Not in Invasive Disease

2004 ◽  
Vol 72 (7) ◽  
pp. 3902-3906 ◽  
Author(s):  
A. R. Kerr ◽  
P. V. Adrian ◽  
S. Estevão ◽  
R. de Groot ◽  
G. Alloing ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Invasive Disease ◽  
Wild Type ◽  
Survival Times ◽  
Triple Mutant ◽  
Nasopharyngeal Colonization ◽  
Atp Binding Cassette Transporter ◽  
Pneumococcal Colonization ◽  
Oligopeptide Permease

ABSTRACT The Ami-AliA/AliB oligopeptide permease is an ATP-binding cassette transporter which is found in Streptococcus pneumoniae and which is involved in nutrient uptake. We investigated the role of the three paralogous oligopeptide-binding lipoproteins AmiA, AliA, and AliB by using murine models of pneumococcal colonization and invasive disease. A series of mutants lacking aliA, aliB, and amiA either alone or in combination as double or triple mutations were used. Inoculation of the nasopharynx with a mixture of the obl (oligopeptide-binding lipoprotein-negative) triple-mutant and wild-type (D39) bacteria resulted in significantly smaller numbers of obl bacteria colonizing the nasopharynx. The use of a mixture of individual mutants and wild-type pneumococci revealed that AmiA, AliA, and AliB were all required for successful colonization of the nasopharynx. The obl mutant was more attenuated than the aliB mutant but not the aliA or amiA mutant. Therefore, there is some redundancy in the Ami-AliA/AliB complex in terms of nasopharyngeal colonization, with AliA and AmiA being able to compensate for the removal of AliB. Animals with invasive disease caused by these mutants had survival times, bacterial loads, and inflammatory cytokine production levels similar to those of animals infected with wild-type pneumococci. Our results show that although the Ami-AliA/AliB complex is not required for virulence during pneumococcal pneumonia, it does play a role in colonization of the nasopharynx.

scholarly journals Limited Role of Antibody in Clearance of Streptococcus pneumoniae in a Murine Model of Colonization

2004 ◽  
Vol 72 (10) ◽  
pp. 5807-5813 ◽  
Author(s):  
Tera L. McCool ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Parent Strain ◽  
Lower Respiratory Tract ◽  
Serum Antibody ◽  
Inbred Strains ◽  
Invasive Disease ◽  
Inbred Strains Of Mice ◽  
Polysaccharide Antigens ◽  
Pneumococcal Colonization

ABSTRACT Colonization is the first step in the interaction between Streptococcus pneumoniae and its human host. To better understand the mechanisms contributing to natural carriage, a mouse model of pneumococcal colonization was developed with a clinical isolate of S. pneumoniae previously characterized in experimental colonization of humans. Similar to carriage events in humans, colonization of mice was self-limited and there was no evidence of lower respiratory tract or invasive disease. Carriage induced a serum antibody response to whole pneumococci that was associated temporally with clearance of colonization in three inbred strains of mice. Individual mice, however, did not demonstrate a correlation between the density of colonization and amounts of serum or of mucosal antibodies, including antibodies of different isotypes and antigenic specificities. The role of antibody in the clearance of carriage was then examined in mice with genetic defects in humoral immunity. xid mice, which have deficient responses to polysaccharide antigens, cleared colonization at the same rate as the parent strain. Finally, we showed that μMT mice, which lack mature B cells and fail to produce antibody, were unaffected in the density or duration of colonization. These results demonstrate that antibody is not required for clearance of pneumococcal colonization in mice.

scholarly journals Immunization with Recombinant Streptococcus pneumoniae Neuraminidase NanA Protects Chinchillas against Nasopharyngeal Colonization

2005 ◽  
Vol 73 (11) ◽  
pp. 7775-7778 ◽  
Author(s):  
H. H. Tong ◽  
D. Li ◽  
S. Chen ◽  
J. P. Long ◽  
T. F. DeMaria
Keyword(s):  
Streptococcus Pneumoniae ◽  
Control Cohort ◽  
Nasopharyngeal Colonization ◽  
Pneumococcal Colonization

ABSTRACT Immunization with recombinant S. pneumoniae neuraminidase NanA (rNanA) resulted in a significant reduction in pneumococcal colonization in the chinchilla model. The bacteria were eliminated from the nasopharynx 1 week earlier than that from the control cohort. Our data suggest that rNanA affords protection against pneumococcal nasopharyngeal colonization.

scholarly journals Protection against Nasopharyngeal Colonization by Streptococcus pneumoniae Is Mediated by Antigen-Specific CD4+ T Cells

2008 ◽  
Vol 76 (6) ◽  
pp. 2678-2684 ◽  
Author(s):  
Krzysztof Trzciński ◽  
Claudette M. Thompson ◽  
Amit Srivastava ◽  
Alan Basset ◽  
Richard Malley ◽  
...  
Keyword(s):  
T Cells ◽  
Streptococcus Pneumoniae ◽  
T Cell ◽  
Protein A ◽  
Specific Antigen ◽  
Surface Protein ◽  
Bacterial Clearance ◽  
Antigen Specificity ◽  
Nasopharyngeal Colonization ◽  
Pneumococcal Colonization

ABSTRACT CD4+ T-cell-dependent acquired immunity confers antibody-independent protection against pneumococcal colonization. Since this mechanism is poorly understood for extracellular bacteria, we assessed the antigen specificity of the induction and recall of this immune response by using BALB/c DO11.10Rag−/− mice, which lack mature B and T cells except for CD4+ T cells specific for the OVA323-339 peptide derived from ovalbumin. Serotype 6B Streptococcus pneumoniae strain 603S and unencapsulated strain Rx1ΔlytA were modified to express OVA323-339 as a fusion protein with surface protein A (PspA) (strains 603OVA1 and Rx1ΔlytAOVA1) or with PspA, neuraminidase A, and pneumolysin (Rx1ΔlytAOVA3). Whole-cell vaccines (WCV) were made of ethanol-killed cells of Rx1ΔlytA plus cholera toxin (CT) adjuvant, of Rx1ΔlytAOVA1 + CT (WCV-OVA1), and of Rx1ΔlytAOVA3 + CT (WCV-OVA3). Mice intranasally immunized with WCV-OVA1, but not with WCV or CT alone, were protected against intranasal challenge with 603OVA1. There was no protection against strain 603S in mice immunized with WCV-OVA1. These results indicate antigen specificity of both immune induction and the recall response. Effector action was not restricted to antigen-bearing bacteria since colonization by 603S was reduced in animals immunized with vaccines made of OVA-expressing strains when ovalbumin or killed Rx1ΔlytAOVA3 antigen was administered around the time of challenge. CD4+ T-cell-mediated protection against pneumococcal colonization can be induced in an antigen-specific fashion and requires specific antigen for effective bacterial clearance, but this activity may extend beyond antigen-expressing bacteria. These results are consistent with the recruitment and/or activation of phagocytic or other nonspecific effectors by antigen-specific CD4+ T cells.

scholarly journals Should Pneumococcal Vaccines Eliminate Nasopharyngeal Colonization?

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Larry S. McDaniel ◽  
Edwin Swiatlo
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Infection ◽  
Invasive Disease ◽  
Pneumococcal Vaccines ◽  
Human Pathogen ◽  
Next Generation ◽  
Nasopharyngeal Colonization ◽  
Conjugate Vaccines ◽  
Pneumococcal Conjugate Vaccines

ABSTRACT  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.

scholarly journals Nasopharyngeal Colonization and Invasive Disease Are Enhanced by the Cell Wall Hydrolases LytB and LytC of Streptococcus pneumoniae

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23626 ◽  
Author(s):  
Elisa Ramos-Sevillano ◽  
Miriam Moscoso ◽  
Pedro García ◽  
Ernesto García ◽  
Jose Yuste
Keyword(s):  
Cell Wall ◽  
Streptococcus Pneumoniae ◽  
Invasive Disease ◽  
Nasopharyngeal Colonization ◽  
Cell Wall Hydrolases

scholarly journals Experimental Human Challenge Reveals Distinct Mechanisms of Acquisition or Protection Against Pneumococcal Colonization

2018 ◽  
Author(s):  
Elissavet Nikolaou ◽  
Simon P. Jochems ◽  
Elena Mitsi ◽  
Sherin Pojar ◽  
Edessa Negera ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Sampling Method ◽  
Invasive Disease ◽  
Upper Respiratory Tract ◽  
Post Challenge ◽  
Upper Respiratory ◽  
Density Dynamics ◽  
Human Immune ◽  
Pneumococcal Colonization

AbstractColonization of the upper respiratory tract with Streptococcus pneumoniae is the precursor of pneumococcal pneumonia and invasive disease. Following exposure, however, it is unclear which human immune mechanisms determine whether a pathogen will colonize. We used a human challenge model to investigate host-pathogen interactions in the first hours and days following intranasal exposure to Streptococcus pneumoniae. Using a novel home sampling method, we measured early immune responses and bacterial density dynamics in the nose and saliva after pneumococcal exposure. We found that nasal colonization can take up to 24 hours to become established. Also, two distinct bacterial clearance profiles were associated with protection: nasal clearers with immediate clearance of bacteria in the nose by the activity of pre-existent mucosal neutrophils and saliva clearers with detectable pneumococcus in saliva at one-hour post challenge and delayed clearance mediated by an inflammatory response and increased neutrophil activity 24 hours post bacterial encounter.

scholarly journals Dynamic changes in innate immune and T cell function and composition at the nasal mucosa across the human lifespan

2019 ◽  
Author(s):  
Jesús Reiné ◽  
Beatriz F. Carniel ◽  
Carla Solórzano ◽  
Elena Mitsi ◽  
Sherin Pojar ◽  
...  
Keyword(s):  
Immune System ◽  
Streptococcus Pneumoniae ◽  
T Cell ◽  
Young Children ◽  
Nasal Mucosa ◽  
Immune Cells ◽  
Nasopharyngeal Colonization ◽  
System Changes ◽  
Pneumococcal Colonization ◽  
Increased Susceptibility

AbstractThe very young and very old are at increased risk of serious infections, including pneumonia. This may relate to changes in the immune system as young children have limited immunological memory, while immunosenescence, inflammaging and a decreased pool of naïve immune cells are described with advanced age. How the immune system changes with age at mucosal surfaces, from where infections frequently develop, is not very clear as access to human tissue samples is limited. Therefore, we aimed to assess the composition and activation state of the immune system at the human mucosa. Here, we profiled nasal immune cells from 207 individuals between 1 to 80 years old using flow cytometry. Neutrophil and monocyte functionality were measured using whole blood assays. Levels of thirty nasal cytokines were measured from nasal lining fluid. Nasopharyngeal colonization by Streptococcus pneumoniae was assessed using classical microbiology and associated with immune responses. We found that young children have a striking paucity of granulocytes at the nasal mucosa compared to adults. In addition, T cell numbers at the nasal mucosa decreased progressively with age and were almost absent in older adults. While nasopharyngeal colonization by Streptococcus pneumoniae was associated with elevated levels of inflammation it had a limited effect on nasal immune composition, including levels of monocytes and neutrophils. These results show that the immune system at the nasal mucosal surface changes drastically with age and provides explanations for the increased susceptibility to infections in young and old age.Significance statementHow the immune system changes with age is an intensive area of research, but has been primarily studied in blood. However, blood poorly reflects the immune system at the mucosa, from where infections develop. This manuscript provides a first characterization of how the composition and function of the immune system in the upper respiratory tract changes with age, providing explanations for increased susceptibility to infection in the very young and old. Furthermore, by linking mucosal and systemic measurements with pneumococcal colonization, we observed that reduced monocyte and neutrophil responses associate with the increased burden of pneumococcal colonization in children. This study highlights the need to study the immune system also at other mucosal sites in the context of aging.

scholarly journals Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae

Microbiology ◽  
2011 ◽  
Vol 157 (2) ◽  
pp. 504-515 ◽  
Author(s):  
Pratik Shah ◽  
Bindu Nanduri ◽  
Edwin Swiatlo ◽  
Yinfa Ma ◽  
Ken Pendarvis
Keyword(s):  
Streptococcus Pneumoniae ◽  
Invasive Disease ◽  
Therapeutic Interventions ◽  
Transport Mechanisms ◽  
Wild Type ◽  
Polyamine Biosynthesis ◽  
Transport Pathways ◽  
Polyamine Transport ◽  
Mutant Strains ◽  
Pneumococcal Colonization

Polyamines such as cadaverine, putrescine and spermidine are polycationic molecules that have pleiotropic effects on cells via their interaction with nucleic acids. Streptococcus pneumoniae (the pneumococcus) is a Gram-positive pathogen capable of causing pneumonia, septicaemia, otitis media and meningitis. Pneumococci have a polyamine transport operon (potABCD) responsible for the binding and transport of putrescine and spermidine, and can synthesize cadaverine and spermidine using their lysine decarboxylase (cad) and spermidine synthase (speE) enzymes. Previous studies from our laboratory have shown that an increase in PotD expression is seen following exposure to various stresses, while during infection, potD inactivation significantly attenuates pneumococcal virulence, and anti-PotD immune responses are protective in mice. In spite of their relative importance, not much is known about the global contribution of polyamine biosynthesis and transport pathways to pneumococcal disease. Mutants deficient in polyamine biosynthesis (ΔspeE or Δcad) or transport genes (ΔpotABCD) were constructed and were found to be attenuated in murine models of pneumococcal colonization and pneumonia, either alone or in competition with the wild-type strain. The ΔspeE mutant was also attenuated during invasive disease, while the potABCD and cad genes seemed to be dispensable. HPLC analyses showed reduced intracellular polyamine levels in all mutant strains compared with wild-type bacteria. High-throughput proteomic analyses indicated reduced expression of growth, replication and virulence factors in mutant strains. Thus, polyamine biosynthesis and transport mechanisms are intricately linked to the fitness, survival and pathogenesis of the pneumococcus in host microenvironments, and may represent important targets for prophylactic and therapeutic interventions.

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