Synergistic inhibition of pneumococcal growth by Dolosigranulum pigrum and Corynebacterium pseudodiphtheriticum: insights into nasopharyngeal microbial interactions.
Por:
Cisneros M, Blanco-Fuertes M, Lluansí A, Brotons-de los Reyes P, Henares-Bonilla D, Pérez-Argüello A, González-Comino G, Ciruela Navas P, Mira A and Munoz-Almagro C
Publicada:
1 jul 2025
Ahead of Print:
30 may 2025
Resumen:
Streptococcus pneumoniae is a nasopharynx colonizer that can invade sterile tissues, causing invasive pneumococcal disease (IPD). Dolosigranulum pigrum and Corynebacterium pseudodiphtheriticum are commensal bacteria commonly isolated from the nasopharynx of healthy children, potentially playing a protective role. This study aims to analyze the effects of D. pigrum and C. pseudodiphtheriticum on S. pneumoniae in vitro growth. Pneumococcal strains were collected from IPD patients and healthy carriers in Catalonia (2016-2023). D. pigrum and C. pseudodiphtheriticum strains were isolated from a healthy child's nasopharynx. S. pneumoniae was co-cultured with each commensal bacterium in triplicate experiments. Pneumococcal growth was quantified using a real-time PCR assay targeting the lytA gene. The effect of commensal bacteria on pneumococcal growth was evaluated using a linear mixed-effect regression model. Twenty-eight pneumococcal strains expressing 24 different serotypes and 27 clonal types were analyzed (18 isolated in blood and 10 in nasopharyngeal aspirate). Pneumococcal growth was decreased by D. pigrum (ß = -0.763, 95% confidence interval [CI]: -0.94 to -0.59, P < 0.0001) and C. pseudodiphtheriticum (ß = -0.583, 95% CI: -0.76 to -0.41, P < 0.0001). The combined presence of both had a stronger inhibitory effect (ß = -0.971, 95% CI: -1.15 to -0.79, P < 0.0001). No association was found between isolation site or serotype with pneumococcal growth. D. pigrum and C. pseudodiphtheriticum significantly reduced pneumococcal growth, with a synergistic effect when combined. This antagonistic effect supports the potential protective factor of healthy nasopharyngeal microbiota against IPD and the development of these microorganisms as probiotics.IMPORTANCEInvasive pneumococcal disease (IPD) is a significant worldwide health challenge. The present study highlights the significant inhibitory effect of two commensal bacteria, Dolosigranulum pigrum and Corynebacterium pseudodiphtheriticum, on pneumococcal growth, with a stronger effect observed when both bacteria are present together. Through testing different strains of S. pneumoniae and the implementation of a robust statistical model, this research advances in the knowledge of microbial ecology and provides evidence to support the development of the use of these commensal bacteria as probiotics. These results emphasize the possibility of using the nasopharyngeal microbiota's natural interactions to mitigate the risk of IPD.
Filiaciones:
Cisneros M:
Grup de Recerca, Institut de Recerca Sant Joan de Déu (IRSJD), Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain. RINGGOLD: 16512
Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Catalonia, Spain. RINGGOLD: 120014
:
Grup de Recerca, Institut de Recerca Sant Joan de Déu (IRSJD), Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain. RINGGOLD: 16512
CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain. RINGGOLD: 38176. ROR: https://ror.org/00ca2c886
Lluansí A:
Grup de Recerca, Institut de Recerca Sant Joan de Déu (IRSJD), Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain. RINGGOLD: 16512
CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain. RINGGOLD: 38176. ROR: https://ror.org/00ca2c886
Brotons-de los Reyes P:
Grup de Recerca, Institut de Recerca Sant Joan de Déu (IRSJD), Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain. RINGGOLD: 16512
Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Catalonia, Spain. RINGGOLD: 120014
CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain. RINGGOLD: 38176. ROR: https://ror.org/00ca2c886
Henares-Bonilla D:
Grup de Recerca, Institut de Recerca Sant Joan de Déu (IRSJD), Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain. RINGGOLD: 16512
CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain. RINGGOLD: 38176. ROR: https://ror.org/00ca2c886
Pérez-Argüello A:
Grup de Recerca, Institut de Recerca Sant Joan de Déu (IRSJD), Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain. RINGGOLD: 16512
:
Grup de Recerca, Institut de Recerca Sant Joan de Déu (IRSJD), Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain. RINGGOLD: 16512
Ciruela Navas P:
CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain. RINGGOLD: 38176. ROR: https://ror.org/00ca2c886
Agència de Salut Pública de Catalunya, Barcelona, Catalonia, Spain. RINGGOLD: 535551. ROR: https://ror.org/0301ppm60
Mira A:
CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain. RINGGOLD: 38176. ROR: https://ror.org/00ca2c886
Genomics and Health Department, FISABIO Foundation, Valencia, Valencian Community, Spain. RINGGOLD: 203353
Munoz-Almagro C:
Grup de Recerca, Institut de Recerca Sant Joan de Déu (IRSJD), Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain. RINGGOLD: 16512
Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Catalonia, Spain. RINGGOLD: 120014
CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Community of Madrid, Spain. RINGGOLD: 38176. ROR: https://ror.org/00ca2c886
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