Abstract
Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal cavity mediated, in part, by polymicrobial communities of bacteria. Recent molecular studies have confirmed the importance of Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) in CRS. Here, we hypothesize that interaction between S. pneumoniae and NTHi mixed-species communities cause a change in bacterial virulence gene expression. We examined CRS as a model human disease to validate these polymicrobial interactions. Clinical strains of S. pneumoniae and NTHi were grown in mono- and co-culture in a standard biofilm assay. Reverse transcriptase real-time PCR (RTqPCR) was used to measure gene expression of key virulence factors. To validate these results, we investigated the presence of the bacterial RNA transcripts in excised human tissue from patients with CRS. Consequences of physical or chemical interactions between microbes were also investigated. Transcription of NTHi type IV pili was only expressed in co-culture in vitro, and expression could be detected ex vivo in diseased tissue. S. pneumoniae pyruvate oxidase was up-regulated in co-culture, while pneumolysin and pneumococcal adherence factor A were down-regulated. These results were confirmed in excised human CRS tissue. Gene expression was differentially regulated by physical contact and secreted factors. Overall, these data suggest that interactions between H. influenzae and S. pneumoniae involve physical and chemical mechanisms that influence virulence gene expression of mixed-species biofilm communities present in chronically diseased human tissue. These results extend previous studies of population-level virulence and provide novel insight into the importance of S. pneumoniae and NTHi in CRS.
Highlights
The current paradigm of one organism causing disease has been valuable in treating acute infections, it has become clear that many chronic bacterial infections are comprised of mixedspecies microbial communities
To confirm that gene regulation observed in co-culture biofilms was not a product of cellular death or inhibition of growth, we measured the optical density of mono- and co-culture bacteria over 10 hours of planktonic growth
We investigated the regulation of virulence determinants in S. pneumoniae and H. influenzae clinical isolates as a function of community interactions
Summary
The current paradigm of one organism causing disease has been valuable in treating acute infections, it has become clear that many chronic bacterial infections are comprised of mixedspecies microbial communities. Microbial species exist interdependently among each other and with the host. This balance is delicate, and a shift in relative abundances within these complex communities can lead to chronic infection [1,2,3,4,5,6]. This paper introduced the idea that interactions among specific microbial communities produce increased or attenuated virulence profiles. In accord with this observation, Ehrlich and colleagues established ‘bacterial plurality’ as a new rubric for understanding chronic infections. We examine chronic rhinosinusitis (CRS) as a model human disease to describe polymicrobial interactions
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