Synergistic inhibition of pneumococcal growth by Dolosigranulum pigrum and Corynebacterium pseudodiphtheriticum: insights into nasopharyngeal microbial interactions

Abstract

ABSTRACT 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 (β = −0.763, 95% confidence interval [CI]: −0.94 to −0.59, P < 0.0001) and C. pseudodiphtheriticum (β = −0.583, 95% CI: −0.76 to −0.41, P < 0.0001). The combined presence of both had a stronger inhibitory effect (β = −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.