Abstract

Streptococcus mitis (S. mitis) and Pseudomonas aeruginosa (P. aeruginosa) are typically found in the upper respiratory tract of infants. We previously found that P. aeruginosa and S. mitis were two of the most common bacteria in biofilms on newborns’ endotracheal tubes (ETTs) and in their sputa and that S. mitis was able to produce autoinducer-2 (AI-2), whereas P. aeruginosa was not. Recently, we also found that exogenous AI-2 and S. mitis could influence the behaviors of P. aeruginosa. We hypothesized that S. mitis contributes to this interspecies interaction and that inhibition of AI-2 could result in inhibition of these effects. To test this hypothesis, we selected PAO1 as a representative model strain of P. aeruginosa and evaluated the effect of S. mitis as well as an AI-2 analog (D-ribose) on mono- and co-culture biofilms in both in vitro and in vivo models. In this context, S. mitis promoted PAO1 biofilm formation and pathogenicity. Dual-species (PAO1 and S. mitis) biofilms exhibited higher expression of quorum sensing genes than single-species (PAO1) biofilms did. Additionally, ETTs covered in dual-species biofilms increased the mortality rate and aggravated lung infection compared with ETTs covered in mono-species biofilms in an endotracheal intubation rat model, all of which was inhibited by D-ribose. Our results demonstrated that S. mitis AI-2 plays an important role in interspecies interactions with PAO1 and may be a target for inhibition of biofilm formation and infection in ventilator-associated pneumonia.

Highlights

  • Interactions among diverse microbial species are dynamic and most likely propel many adaptations, such as biofilm formation in host respiratory tracts and multiple marine habitats (DeLong, 2009; Conway et al, 2012)

  • We focused on the influence of S. mitis and D-ribose on PAO1 and evaluated the effects on biofilm formation, virulence and the expression of PAO1 quorum sensing (QS) genes

  • The 50 mM concentration of D-ribose did not influence the growth of the planktonic PAO1 cultures, whereas it induced the growth of S. mitis in the stationary phase (Figure 2A)

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Summary

Introduction

Interactions among diverse microbial species are dynamic and most likely propel many adaptations, such as biofilm formation in host respiratory tracts and multiple marine habitats (DeLong, 2009; Conway et al, 2012) These interspecies interactions involve the action of multiple genetic and metabolic pathways, which can result in mutualistic or antagonistic effects on bacteria (Xie et al, 2008; Rogers et al, 2010; Conway et al, 2012). When different microbes within a community interact with each other, the resulting pathogenesis differs from that of infections caused by the individual component species In such a context that involves a complex polymicrobial community, single-species microbial analyses are inadequate, not providing much insight into the ecological dynamics of natural habitats (Wagner and Iglewski, 2008; Hibbing et al, 2010; Rogers et al, 2010). We found that exogenous autoinducer-2 (AI-2) and S. mitis could influence the behaviors of P. aeruginosa (Li et al, 2015a; Song et al, 2015)

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