Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy.

2021

2021 Sep 11

1751-7370

<p>Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify interspecies interactions that modify the risk of S. pneumoniae colonization during infancy and to describe development of the upper respiratory microbiome during infancy in a sub-Saharan African setting. We collected nasopharyngeal swabs monthly (0-6 months of age) or bimonthly (6-12 months of age) from 179 mother-infant dyads in Botswana. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and identified S. pneumoniae colonization using a species-specific PCR assay. We detect S. pneumoniae colonization in 144 (80%) infants at a median age of 71 days and identify a strong negative association between the relative abundance of the bacterial genera Corynebacterium within the infant nasopharyngeal microbiome and the risk of S. pneumoniae colonization. Using in vitro cultivation experiments, we demonstrate growth inhibition of S. pneumoniae by secreted factors from strains of several Corynebacterium species isolated from these infants. Finally, we demonstrate that antibiotic exposures and the winter season are associated with a decline in the relative abundance of Corynebacterium within the nasopharyngeal microbiome, while breastfeeding is associated with an increase in the Corynebacterium relative abundance. Our findings provide novel insights into the interspecies interactions that contribute to colonization resistance to S. pneumoniae and suggest that the nasopharyngeal microbiome may be a previously unrecognized mechanism by which environmental factors influence the risk of pneumococcal infections during childhood. Moreover, this work lays the foundation for future studies seeking to use targeted manipulation of the nasopharyngeal microbiome to prevent infections caused by S. pneumoniae.</p>

10.1038/s41396-021-01108-4

ISME J

34511605

Pneumococcal Colonization and the Nasopharyngeal Microbiota of Children in Botswana.

2018

2018 Aug 27

1532-0987

<p><strong>BACKGROUND: </strong>Nasopharyngeal colonization precedes infections caused by Streptococcus pneumoniae. A more detailed understanding of interactions between S. pneumoniae and the nasopharyngeal microbiota of children could inform strategies to prevent pneumococcal infections.</p>

<p><strong>METHODS: </strong>We collected nasopharyngeal swabs from children 1 to 23 months of age in Botswana between August 2012 and June 2016. We tested samples for S. pneumoniae and common respiratory viruses using PCR. We sequenced the V3 region of the bacterial 16S ribosomal RNA gene and used random forest models to identify clinical variables and bacterial genera that were associated with pneumococcal colonization.</p>

<p><strong>RESULTS: </strong>Mean age of the 170 children included in this study was 8.3 months. Ninety-six (56%) children were colonized with S. pneumoniae. Pneumococcal colonization was associated with older age (P=0.0001), a lack of electricity in the home (P=0.02), and household use of wood as a cooking fuel (P=0.002). Upper respiratory symptoms were more frequent in children with S. pneumoniae colonization (60% vs. 32%; P=0.001). Adjusting for age, nasopharyngeal microbiota composition differed in colonized and noncolonized children (P=0.001). S. pneumoniae colonization was associated with a higher relative abundance of Moraxella (P=0.001) and lower relative abundances of Corynebacterium (P=0.001) and Staphylococcus (P=0.03). A decision tree model containing the relative abundances of bacterial genera had 81% sensitivity and 85% specificity for the determination of S. pneumoniae colonization status.</p>

<p><strong>CONCLUSIONS: </strong>S. pneumoniae colonization is associated with characteristic alterations of the nasopharyngeal microbiota of children. Prospective studies should determine if nasopharyngeal microbial composition alters the risk of pneumococcal colonization and thus could be modified as a novel pneumonia prevention strategy.</p>

10.1097/INF.0000000000002174

Pediatr. Infect. Dis. J.

30153231

The Nasopharyngeal Microbiota of Children with Respiratory Infections in Botswana.

2017

2017 Apr 10

1532-0987

<p><strong>BACKGROUND: </strong>Nearly half of child pneumonia deaths occur in sub-Saharan Africa. Microbial communities in the nasopharynx are a reservoir for pneumonia pathogens and remain poorly described in African children.</p>

<p><strong>METHODS: </strong>Nasopharyngeal swabs were collected from children with pneumonia (N=204), children with upper respiratory infection symptoms (N=55), and healthy children (N=60) in Botswana between April 2012 and April 2014. We sequenced the V3 region of the bacterial 16S ribosomal RNA gene and used partitioning around medoids to cluster samples into microbiota biotypes. We then used multivariable logistic regression to examine whether microbiota biotypes were associated with pneumonia and upper respiratory infection symptoms.</p>

<p><strong>RESULTS: </strong>Mean ages of children with pneumonia, children with upper respiratory infection symptoms, and healthy children were 8.2, 11.4, and 8.0 months, respectively. Clustering of nasopharyngeal microbiota identified five distinct biotypes: Corynebacterium/Dolosigranulum-dominant (23%), Haemophilus-dominant (11%), Moraxella-dominant (24%), Staphylococcus-dominant (13%), and Streptococcus-dominant (28%). The Haemophilus-dominant [odds ratio (OR): 13.55, 95% confidence interval (CI): 2.10-87.26], the Staphylococcus-dominant (OR: 8.27, 95% CI: 2.13-32.14), and the Streptococcus-dominant (OR: 39.97, 95% CI: 6.63-241.00) biotypes were associated with pneumonia. The Moraxella-dominant (OR: 3.71, 95% CI: 1.09-12.64) and Streptococcus-dominant (OR: 12.26, 95% CI: 1.81-83.06) biotypes were associated with upper respiratory infection symptoms. In children with pneumonia, HIV infection was associated with a lower relative abundance of Dolosigranulum (P=0.03).</p>

<p><strong>CONCLUSIONS: </strong>Pneumonia and upper respiratory infection symptoms are associated with distinct nasopharyngeal microbiota biotypes in African children. A lower abundance of the commensal genus Dolosigranulum may contribute to the higher pneumonia risk of HIV-infected children.</p>

10.1097/INF.0000000000001607

Pediatr. Infect. Dis. J.

28399056