scholarly journals Streptococcus pneumoniae Transmission Is Blocked by Type-Specific Immunity in an Infant Mouse Model

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Tonia Zangari ◽  
Yang Wang ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mouse Model ◽  
Pneumococcal Conjugate Vaccine ◽  
Herd Immunity ◽  
Mechanistic Explanation ◽  
Epidemiological Studies ◽  
Contributing Factors ◽  
Infant Mouse ◽  
Major Benefit

ABSTRACT Epidemiological studies on Streptococcus pneumoniae show that rates of carriage are highest in early childhood and that the major benefit of the pneumococcal conjugate vaccine (PCV) is a reduction in the incidence of nasopharyngeal colonization through decreased transmission within a population. In this study, we sought to understand how anti- S. pneumoniae immunity affects nasal shedding of bacteria, the limiting step in experimental pneumococcal transmission. Using an infant mouse model, we examined the role of immunity (passed from mother to pup) on shedding and within-litter transmission of S. pneumoniae by pups infected at 4 days of life. Pups from both previously colonized immune and PCV-vaccinated mothers had higher levels of anti- S. pneumoniae IgG than pups from non-immune or non-vaccinated mothers and shed significantly fewer S. pneumoniae over the first 5 days of infection. By setting up cross-foster experiments, we demonstrated that maternal passage of antibody to pups either in utero or post-natally decreases S. pneumoniae shedding. Passive immunization experiments showed that type-specific antibody to capsular polysaccharide is sufficient to decrease shedding and that the agglutinating function of immunoglobulin is required for this effect. Finally, we established that anti-pneumococcal immunity and anti-PCV vaccination block host-to-host transmission of S. pneumoniae . Moreover, immunity in either the donor or recipient pups alone was sufficient to reduce rates of transmission, indicating that decreased shedding and protection from acquisition of colonization are both contributing factors. Our findings provide a mechanistic explanation for the reduced levels of S. pneumoniae transmission between hosts immune from prior exposure and among vaccinated children. IMPORTANCE Rates of carriage of the bacterial pathogen Streptococcus pneumoniae are highest among young children, and this is the target group for the pneumococcal conjugate vaccine (PCV). Epidemiological studies have suggested that a major benefit of the PCV is a reduction in host-to-host transmission, which also protects the non-vaccinated population (“herd immunity”). In this study, we examined the role of anti-pneumococcal immunity on nasal shedding and transmission of the pathogen using an infant mouse model. We found that shedding is decreased and transmission is blocked by anti-pneumococcal immunity and PCV vaccination. Additionally, transmission rates decreased if either the infected or contact pups were immune, indicating that reduced shedding and protection from the establishment of colonization are both contributing factors. Our study provides a mechanistic explanation for the herd immunity effect seen after the introduction of PCV and identifies potential points of intervention, which may have implications for future vaccine development.

scholarly journals Streptococcus pneumoniae Serotypes 9 and 14 Circulating in Brazil over a 23-Year Period Prior to Introduction of the 10-Valent Pneumococcal Conjugate Vaccine: Role of International Clones in the Evolution of Antimicrobial Resistance and Description of a Novel Genotype

2016 ◽  
Vol 60 (11) ◽  
pp. 6664-6672 ◽  
Author(s):  
Tatiana C. A. Pinto ◽  
Fabíola C. O. Kegele ◽  
Cícero A. G. Dias ◽  
Rosana R. Barros ◽  
José M. Peralta ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Antimicrobial Resistance ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Susceptibility Testing ◽  
Pneumococcal Vaccination ◽  
Beta Lactams ◽  
Increasing Trend ◽  
The 1960S

ABSTRACTAntimicrobial-resistant pneumococcal strains have been detected worldwide since the 1960s. In Brazil, the first penicillin-nonsusceptible pneumococci (PNSP) were reported in the 1980s, and their emergence and dissemination have been mainly attributed to serogroup 9 and serotype 14 strains, especially those highly related to recognized international clones. In the present study, antimicrobial susceptibility testing and multilocus sequence typing were performed on 315 pneumococcal isolates belonging to serogroup 9 (n= 99) or serotype 14 (n= 216), recovered from patients or asymptomatic carriers between 1988 and 2011 in Brazil, in order to trace changes in antimicrobial resistance and genotypes prior to the full introduction of the pneumococcal conjugate vaccine in the country. Over the 23-year study period, the PNSP levels increased, and four clonal complexes (CC156, CC66, CC15, and CC5401) have played important roles in the evolution and dissemination of pneumococcal isolates belonging to serogroup 9 and serotype 14, as well as in the emergence of antimicrobial resistance, in the pre-pneumococcal-vaccination era. The earliest PNSP strains detected in this study belonged to serotype 9N/ST66 and were single locus variants of the international clone Tennessee14-18 ST67 (CC66). The first serotype 14 PNSP isolates were identified in 1990 and were related to the England14-9 ST9 (CC15) clone. Serotype 14 PNSP variants of the Spain9V-3 ST156 clone with elevated penicillin MICs and nonsusceptibility to other beta-lactams were detected in 1995 and showed an increasing trend over the years. The results also indicated that introduction of ST156 in our region was preceded by the emergence of trimethoprim-sulfamethoxazole resistance and by the dissemination of ST162. In addition to the presence of successful international clones, a novel regional serotype 14 genotype (CC5401) has emerged in 1996.

A novel pneumococcal surface protein K of nonencapsulated Streptococcus pneumoniae promotes transmission among littermates in an infant mouse model with influenza A virus co-infection

2022 ◽  
Author(s):  
Hideki Sakatani ◽  
Masamitsu Kono ◽  
Denisa Nanushaj ◽  
Daichi Murakami ◽  
Saori Takeda ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mouse Model ◽  
Influenza A ◽  
Capsular Polysaccharide ◽  
Surface Protein ◽  
Nasal Colonization ◽  
Infant Mouse ◽  
Key Factor ◽  
Protective Strategy ◽  
New Hosts

We established an infant mouse model for colonization and transmission by nonencapsulated Streptococcus pneumoniae (NESp) strains to gain important information about its virulence among children. Invasive pneumococcal diseases have decreased dramatically since the worldwide introduction of pneumococcal capsular polysaccharide vaccines. Increasing prevalence of non-vaccine serotypes including NESp has been highlighted as a challenge in treatment strategy, but the virulence of NESp is not well understood. Protective strategy against NESp colonization and transmission between children require particularly urgent evaluation. NESp lacks capsules, a major virulent factor of pneumococci, but can cause a variety of infections in children and older people. PspK, a specific surface protein of NESp, is a key factor in establishing nasal colonization. In our infant mouse model for colonization and transmission by NESp strains, NESp could establish stable nasal colonization at the same level as encapsulated serotype 6A in infant mice, and could be transmitted between littermates. Transmission was promoted by NESp surface virulence factor PspK and influenza virus co-infection. However, PspK-deletion mutants lost the ability to colonize and transmit to new hosts. Promotion of NESp transmission by influenza was due to increased susceptibility of the new hosts. PspK was a key factor not only in establishment of nasal colonization, but also in transmission to new hosts. PspK may be targeted as a new candidate vaccine for NESp infection in children.

scholarly journals Capsule Type and Amount Affect Shedding and Transmission of Streptococcus pneumoniae

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
M. Ammar Zafar ◽  
Shigeto Hamaguchi ◽  
Tonia Zangari ◽  
Michael Cammer ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mouse Model ◽  
Human Population ◽  
Capsular Polysaccharide ◽  
Upper Respiratory Tract ◽  
Wild Type ◽  
Infant Mouse ◽  
Capsule Type ◽  
Upper Respiratory ◽  
Epidemiology Studies

ABSTRACT The capsular polysaccharide (CPS) of Streptococcus pneumoniae is characterized by its diversity, as it has over 95 known serotypes, and the variation in its thickness as it surrounds an organism. While within-host effects of CPS have been studied in detail, there is no information about its contribution to host-to-host transmission. In this study, we used an infant mouse model of intralitter transmission, together with isogenic capsule switch and cps promoter switch constructs, to explore the effects of CPS type and amount. The determining factor in the transmission rate in this model is the number of pneumococci shed in nasal secretions by colonized hosts. Two of seven capsule switch constructs showed reduced shedding. These constructs were unimpaired in colonization and expressed capsules similar in size to those of the wild-type strain. A cps promoter switch mutant expressing ~50% of wild-type amounts of CPS also displayed reduced shedding without a defect in colonization. Since shedding from the mucosal surface may require escape from mucus entrapment, a mucin-binding assay was used to compare capsule switch and cps promoter switch mutants. The CPS type or amount constructs that shed poorly were bound more robustly by immobilized mucin. These capsule switch and cps promoter switch constructs with increased mucin-binding affinity and reduced shedding also had lower rates of pup-to-pup transmission. Our results demonstrate that CPS type and amount affect transmission dynamics and may contribute to the marked differences in prevalence among pneumococcal types. IMPORTANCE Streptococcus pneumoniae, a leading cause of morbidity and mortality, is readily transmitted, especially among young children. Its structurally and antigenically diverse capsular polysaccharide is the target of currently licensed pneumococcal vaccines. Epidemiology studies show that only a subset of the >95 distinct serotypes are prevalent in the human population, suggesting that certain capsular polysaccharide types might be more likely to be transmitted within the community. Herein, we used an infant mouse model to show that both capsule type and amount are important determinants in the spread of pneumococci from host to host. Transmission rates correlate with those capsule types that are better at escaping mucus entrapment, a key step in exiting the host upper respiratory tract. Hence, our study provides a better mechanistic understanding of why certain pneumococcal serotypes are more common in the human population. IMPORTANCE Streptococcus pneumoniae, a leading cause of morbidity and mortality, is readily transmitted, especially among young children. Its structurally and antigenically diverse capsular polysaccharide is the target of currently licensed pneumococcal vaccines. Epidemiology studies show that only a subset of the >95 distinct serotypes are prevalent in the human population, suggesting that certain capsular polysaccharide types might be more likely to be transmitted within the community. Herein, we used an infant mouse model to show that both capsule type and amount are important determinants in the spread of pneumococci from host to host. Transmission rates correlate with those capsule types that are better at escaping mucus entrapment, a key step in exiting the host upper respiratory tract. Hence, our study provides a better mechanistic understanding of why certain pneumococcal serotypes are more common in the human population.

scholarly journals An Infant Mouse Model of Influenza Virus Transmission Demonstrates the Role of Virus-Specific Shedding, Humoral Immunity, and Sialidase Expression by ColonizingStreptococcus pneumoniae

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Mila Brum Ortigoza ◽  
Simone B. Blaser ◽  
M. Ammar Zafar ◽  
Alexandria J. Hammond ◽  
Jeffrey N. Weiser
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Virus Strain ◽  
Humoral Immunity ◽  
Disease Spread ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Infant Mouse ◽  
Primary Model

ABSTRACTThe pandemic potential of influenza A viruses (IAV) depends on the infectivity of the host, transmissibility of the virus, and susceptibility of the recipient. While virus traits supporting IAV transmission have been studied in detail using ferret and guinea pig models, there is limited understanding of host traits determining transmissibility and susceptibility because current animal models of transmission are not sufficiently tractable. Although mice remain the primary model to study IAV immunity and pathogenesis, the efficiency of IAV transmission in adult mice has been inconsistent. Here we describe an infant mouse model that supports efficient transmission of IAV. We demonstrate that transmission in this model requires young age, close contact, shedding of virus particles from the upper respiratory tract (URT) of infected pups, the use of a transmissible virus strain, and a susceptible recipient. We characterize shedding as a marker of infectiousness that predicts the efficiency of transmission among different influenza virus strains. We also demonstrate that transmissibility and susceptibility to IAV can be inhibited by humoral immunity via maternal-infant transfer of IAV-specific immunoglobulins and modifications to the URT milieu, via sialidase activity of colonizingStreptococcus pneumoniae. Due to its simplicity and efficiency, this model can be used to dissect the host’s contribution to IAV transmission and explore new methods to limit contagion.IMPORTANCEThis study provides insight into the role of the virus strain, age, immunity, and URT flora on IAV shedding and transmission efficiency. Using the infant mouse model, we found that (i) differences in viral shedding of various IAV strains are dependent on specific hemagglutinin (HA) and/or neuraminidase (NA) proteins, (ii) host age plays a key role in the efficiency of IAV transmission, (iii) levels of IAV-specific immunoglobulins are necessary to limit infectiousness, transmission, and susceptibility to IAV, and (iv) expression of sialidases by colonizingS. pneumoniaeantagonizes transmission by limiting the acquisition of IAV in recipient hosts. Our findings highlight the need for strategies that limit IAV shedding and the importance of understanding the function of the URT bacterial composition in IAV transmission. This work reinforces the significance of a tractable animal model to study both viral and host traits affecting IAV contagion and its potential for optimizing vaccines and therapeutics that target disease spread.

scholarly journals Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection

2016 ◽  
Vol 84 (9) ◽  
pp. 2714-2722 ◽  
Author(s):  
M. Ammar Zafar ◽  
Masamitsu Kono ◽  
Yang Wang ◽  
Tonia Zangari ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mouse Model ◽  
Influenza A ◽  
Carrier State ◽  
High Ratio ◽  
New Host ◽  
Content Type ◽  
Infant Mouse ◽  
Colonization Density ◽  
Pneumococcal Colonization

One of the least understood aspects of the bacteriumStreptococcus pneumoniae(pneumococcus) is its transmission from host to host, the critical first step in both the carrier state and the disease state. To date, transmission models have depended on influenza A virus coinfection, which greatly enhances pneumococcal shedding to levels that allow acquisition by a new host. Here, we describe an infant mouse model that can be utilized to study pneumococcal colonization, shedding, and transmission during bacterial monoinfection. Using this model, we demonstrated that the level of bacterial shedding is highest in pups infected intranasally at age 4 days and peaks over the first 4 days postchallenge. Shedding results differed among isolates of five different pneumococcal types. Colonization density was found to be a major factor in the level of pneumococcal shedding and required expression of capsule. Transmission within a litter occurred when there was a high ratio of colonized “index” pups to uncolonized “contact” pups. Transmission was observed for each of the well-colonizing pneumococcal isolates, with the rate of transmission proportional to the level of shedding. This model can be used to examine bacterial and host factors that contribute to pneumococcal transmission without the effects of viral coinfection.

scholarly journals Increased Nasopharyngeal Bacterial Titers and Local Inflammation Facilitate Transmission of Streptococcus pneumoniae

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Kirsty R. Short ◽  
Patrick C. Reading ◽  
Nancy Wang ◽  
Dimitri A. Diavatopoulos ◽  
Odilia L. Wijburg
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mouse Model ◽  
Influenza A ◽  
Pneumococcal Disease ◽  
Present Report ◽  
Bacterial Load ◽  
Disease Development ◽  
Proinflammatory Response ◽  
Content Type ◽  
Infant Mouse

ABSTRACTThe transmission of the bacteriumStreptococcus pneumoniae(the pneumococcus) marks the first step toward disease development. To date, our ability to prevent pneumococcal transmission has been limited by our lack of understanding regarding the factors which influence the spread of this pathogen. We have previously developed an infant mouse model of pneumococcal transmission which was strictly dependent on influenza A virus (IAV) coinfection of both the experimentally colonized “index mice” and the naive cohoused “contact mice.” Here, we sought to use this model to further elucidate the factors which facilitateS. pneumoniaetransmission. In the present report, we demonstrate that increasing the nasopharyngeal load ofS. pneumoniaein the colonized index mice (via the depletion of neutrophils) and inducing a proinflammatory response in the naive cohoused contact mice (as demonstrated by cytokine production) facilitatesS. pneumoniaetransmission. Thus, these data provide the first insights into the factors that help mediate the spread ofS. pneumoniaethroughout the community.IMPORTANCEStreptococcus pneumoniae(the pneumococcus) is a major cause of worldwide morbidity and mortality and is a leading cause of death among children under the age of five years. Transmission ofS. pneumoniaemarks the first step toward disease development. Therefore, understanding the factors that influence the spread of pneumococci throughout the community plays an essential role in preventing pneumococcal disease. We previously developed the first reproducible infant mouse model for pneumococcal transmission and showed that coinfection with influenza virus facilitates the spread ofS. pneumoniae. Here, we show that increasing the bacterial load in the nasal cavity of colonized individuals as well as inducing an inflammatory response in naive “contact cases” facilitates the spread of pneumococci. Therefore, this study helps to identify the factors which must be inhibited in order to successfully prevent pneumococcal disease.

scholarly journals An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

2018 ◽  
Author(s):  
Mila Brum Ortigoza ◽  
Simone Blaser ◽  
M. Ammar Zafar ◽  
Alexandria Hammond ◽  
Jeffrey N. Weiser
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Virus Strain ◽  
Humoral Immunity ◽  
Close Contact ◽  
Disease Spread ◽  
Upper Respiratory Tract ◽  
Infant Mouse ◽  
Primary Model

ABSTRACTThe pandemic potential of influenza A viruses (IAV) depends on the infectivity of the host, transmissibility of the virus, and susceptibility of the recipient. While virus traits supporting IAV transmission have been studied in detail using ferret and guinea pig models, there is limited understanding of host traits determining transmissibility and susceptibility because current animal models of transmission are not sufficiently tractable. Although mice remain the primary model to study IAV immunity and pathogenesis, the efficiency of IAV transmission in adult mice has been inconsistent. Here we describe an infant mouse model which support efficient transmission of IAV. We demonstrate that transmission in this model requires young age, close contact, shedding of virus particles from the upper respiratory tract (URT) of infected pups, the use of a transmissible virus strain, and a susceptible recipient. We characterize shedding as a marker of infectiousness that predicts the efficiency of transmission among different influenza virus strains. We also demonstrate that transmissibility and susceptibility to IAV can be inhibited by humoral immunity via maternal-infant transfer of IAV-specific immunoglobulins, and modifications to the URT milieu, via sialidase activity of colonizingStreptococcus pneumoniae(Spn). Due to its simplicity and efficiency, this model can be used to dissect the host’s contribution to IAV transmission and explore new methods to limit contagion.IMPORTANCEThis study provides insight into the role of the virus strain, age, immunity, and URT flora on IAV shedding and transmission efficiency. Using the infant mouse model, we found that: (a) differences in viral shedding of various IAV strains is dependent on specific hemagglutinin (HA) and/or neuraminidase (NA) proteins; (b) host age plays a key role in the efficiency of IAV transmission; (c) levels of IAV-specific immunoglobulins are necessary to limit infectiousness, transmission, and susceptibility to IAV; and (d) expression of sialidases by colonizing Spn antagonize transmission by limiting the acquisition of IAV in recipient hosts. Our findings highlight the need for strategies that limit IAV shedding, and the importance of understanding the function of the URT bacterial composition in IAV transmission. This work reinforces the significance of a tractable animal model to study both viral and host traits affecting IAV contagion, and its potential for optimizing vaccines and therapeutics that target disease spread.

The role of tachykinin 1 in a mouse model of trait anxiety

2007 ◽  
Vol 40 (05) ◽  
Author(s):  
L Czibere ◽  
LA Baur-Jaronowski ◽  
P Weber ◽  
B Pütz ◽  
M Panhuysen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Trait Anxiety
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