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 ◽  
...  

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.

2021 ◽  
Vol 27 (2) ◽  
pp. 1-6
Author(s):  
Ashikin Mohd Nordin ◽  
Jean Jun Ong ◽  
Juriza Ismail ◽  
Norazlin Kamal Nor ◽  
Sau Wei Wong ◽  
...  

Streptococcus pneumoniae (S pneumoniae) can cause a wide spectrum of diseases which includes upper respiratory tract infection as well as more severe invasive disease such as meningitis. Meningitis may be caused by invasion of the organism through the blood brain barrier, either via haematological spread or from an adjacent focus of infection such as the ears. We describe two infants with pneumococcal meningitis and silent mastoiditis. They both presented with a classical history to suggest meningitis with no apparent focus of infection. A brain imaging was done in the first infant to look for the underlying cause of his focal seizure and in the second infant, to assess for complications of meningitis, as he had a slow recovery. While they did not have any clinical signs to point towards the diagnosis, they were both diagnosed to have acute mastoiditis from brain imaging. We would like to highlight the importance of brain imaging in excluding silent mastoiditis in infants with meningitis, particularly in those whose clinical course appears atypical.


BMC Medicine ◽  
2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Joseph D. Challenger ◽  
Cher Y. Foo ◽  
Yue Wu ◽  
Ada W. C. Yan ◽  
Mahdi Moradi Marjaneh ◽  
...  

AbstractRelationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.


1977 ◽  
Vol 6 (2) ◽  
pp. 181-182
Author(s):  
j a Yatabe ◽  
K L baldwin ◽  
W J Martin

An obligately anaerobic strain of Streptococcus pneumoniae was isolated from blood culture in a 14-month-old child with an upper respiratory tract infection.


2020 ◽  
Vol 19 (4) ◽  
pp. 353-366 ◽  
Author(s):  
Adriano Arguedas ◽  
Krzysztof Trzciński ◽  
Katherine L. O’Brien ◽  
Daniela M. Ferreira ◽  
Anne L. Wyllie ◽  
...  

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
M. Ammar Zafar ◽  
Alexandria J. Hammond ◽  
Shigeto Hamaguchi ◽  
Weisheng Wu ◽  
Masamitsu Kono ◽  
...  

ABSTRACTHost-to-host transmission is a necessary but poorly understood aspect of microbial pathogenesis. Herein, we screened a genomic library of mutants of the leading respiratory pathogenStreptococcus pneumoniaegenerated by mariner transposon mutagenesis (Tn-Seq) to identify genes contributing to its exit or shedding from the upper respiratory tract (URT), the limiting step in the organism’s transmission in an infant mouse model. Our analysis focused on genes affecting the bacterial surface that directly impact interactions with the host. Among the multiple factors identified was thedltlocus, which addsd-alanine onto lipoteichoic acids (LTA) and thereby increases Toll-like receptor 2-mediated inflammation and resistance to antimicrobial peptides. The more robust proinflammatory response in the presence ofd-alanylation promotes secretions that facilitate pneumococcal shedding and allows for transmission. Expression of thedltlocus is controlled by the CiaRH system, which senses cell wall stress in response to antimicrobial activity, including in response to lysozyme, the most abundant antimicrobial along the URT mucosa. Accordingly, in alysM−/−host, there was no longer an effect of thedltlocus on pneumococcal shedding. Thus, our findings demonstrate how a pathogen senses the URT milieu and then modifies its surface characteristics to take advantage of the host response for transit to another host.IMPORTANCEStreptococcus pneumoniae(the pneumococcus) is a common cause of respiratory tract and invasive infection. The overall effectiveness of immunization with the organism’s capsular polysaccharide depends on its ability to block colonization of the upper respiratory tract and thereby prevent host-to-host transmission. Because of the limited coverage of current pneumococcal vaccines, we carried out an unbiasedin vivotransposon mutagenesis screen to identify pneumococcal factors other than its capsular polysaccharide that affect transmission. One such candidate was expressed by thedltlocus, previously shown to addd-alanine onto the pneumococcal lipoteichoic acid present on the bacterial cell surface. This modification protects against host antimicrobials and augments host inflammatory responses. The latter increases secretions and bacterial shedding from the upper respiratory tract to allow for transmission. Thus, this study provides insight into a mechanism employed by the pneumococcus to successfully transit from one host to another.


Sign in / Sign up

Export Citation Format

Share Document