Corynebacterium Species Inhibit Streptococcus pneumoniae Colonization and Infection of the Mouse Airway

Abstract

The stability and composition of the airway microbiome is an important determinant of respiratory health. Some airway bacteria are considered to be beneficial due to their potential to impede the acquisition and persistence of opportunistic bacterial pathogens such as <i>Streptococcus pneumoniae</i>. Among such organisms, the presence of <i>Corynebacterium</i> species correlates with reduced <i>S. pneumoniae</i> in both adults and children, in whom <i>Corynebacterium</i> abundance is predictive of <i>S. pneumoniae</i> infection risk. Previously, <i>Corynebacterium accolens</i> was shown to express a lipase which cleaves host lipids, resulting in the production of fatty acids that inhibit growth of <i>S. pneumoniae in vitro</i>. However, it was unclear whether this mechanism contributes to <i>Corynebacterium</i>-<i>S. pneumoniae</i> interactions <i>in vivo</i>. To address this question, we developed a mouse model for <i>Corynebacterium</i> colonization in which colonization with either <i>C. accolens</i> or another species, <i>Corynebacterium amycolatum</i>, significantly reduced <i>S. pneumoniae</i> acquisition in the upper airway and infection in the lung. Moreover, the lungs of co-infected mice had reduced pro-inflammatory cytokines and inflammatory myeloid cells, indicating resolution of infection-associated inflammation. The inhibitory effect of <i>C. accolens</i> on <i>S. pneumoniae in vivo</i> was mediated by lipase-dependent and independent effects, indicating that both this and other bacterial factors contribute to <i>Corynebacterium</i>-mediated protection in the airway. We also identified a previously uncharacterized bacterial lipase in <i>C. amycolatum</i> that is required for inhibition of <i>S. pneumoniae</i> growth <i>in vitro</i>. Together, these findings demonstrate the protective potential of airway <i>Corynebacterium</i> species and establish a new model for investigating the impact of commensal microbiota, such as <i>Corynebacterium</i>, on maintaining respiratory health.