AUTHOR=Wang Zhengli , Xiang Qingqing , Yang Ting , Li Luquan , Yang Jingli , Li Hongong , He Yu , Zhang Yunhui , Lu Qi , Yu Jialin 

TITLE=Autoinducer-2 of Streptococcus mitis as a Target Molecule to Inhibit Pathogenic Multi-Species Biofilm Formation In Vitro and in an Endotracheal Intubation Rat Model

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00088

DOI=10.3389/fmicb.2016.00088

ISSN=1664-302X

ABSTRACT=<p><italic>Streptococcus mitis</italic> (<italic>S. mitis</italic>) and <italic>Pseudomonas aeruginosa</italic> (<italic>P. aeruginosa</italic>) are typically found in the upper respiratory tract of infants. We previously found that <italic>P. aeruginosa</italic> and <italic>S. mitis</italic> were two of the most common bacteria in biofilms on newborns’ endotracheal tubes (ETTs) and in their sputa and that <italic>S. mitis</italic> was able to produce autoinducer-2 (AI-2), whereas <italic>P. aeruginosa</italic> was not. Recently, we also found that exogenous AI-2 and <italic>S. mitis</italic> could influence the behaviors of <italic>P. aeruginosa</italic>. We hypothesized that <italic>S. mitis</italic> 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 <italic>P. aeruginosa</italic> and evaluated the effect of <italic>S. mitis</italic> as well as an AI-2 analog (<sc>D</sc>-ribose) on mono- and co-culture biofilms in both <italic>in vitro</italic> and <italic>in vivo</italic> models. In this context, <italic>S. mitis</italic> promoted PAO1 biofilm formation and pathogenicity. Dual-species (PAO1 and <italic>S. mitis</italic>) 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 <sc>D</sc>-ribose. Our results demonstrated that <italic>S. mitis</italic> 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.</p>