AUTHOR=Yamashita Yu , Nagaoka Kentaro , Kimura Hiroki , Suzuki Masaru , Fukumoto Tatsuya , Hayasaka Kasumi , Kaku Norihito , Morinaga Yoshitomo , Yanagihara Katsunori , Konno Satoshi 

TITLE=Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin Expression

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.587235

DOI=10.3389/fmicb.2020.587235

ISSN=1664-302X

ABSTRACT=<p><bold>Background</bold>: Methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA) is a common causative agent of pneumonia; however, the detailed mechanism underlying severe MRSA pneumonia, including association with oral hygiene or periodontitis, remains poorly characterized. In this study, we examined the pathogenic effect of <italic>Prevotella intermedia</italic>, a major periodontopathic pathogen, on MRSA pneumonia.</p><p><bold>Methods</bold>: The pathogenic effect of the supernatant of <italic>P. intermedia</italic> (Pi Sup) was investigated in a murine MRSA pneumonia model, using several clinical strains; whereas the bactericidal activity of polymorphonuclear leukocytes (PMNs) was investigated <italic>in vitro</italic>. The effect of Pi Sup on messenger RNA (mRNA) expression of the toxin/quorum sensing system (rnaIII) was investigated by quantitative reverse transcription PCR both <italic>in vitro</italic> and <italic>in vivo</italic>.</p><p><bold>Results</bold>: Mice infected by hospital-acquired MRSA (HA-MRSA) with Pi Sup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, and higher α-hemolysin (hla) expression in the lungs, than those without Pi Sup. A similar effect of Pi Sup was not observed with MRSA strains producing Panton-Valentine leucocidin (PVL) or toxic shock syndrome toxin (TSST). <italic>In vitro</italic>, Pi Sup suppressed bactericidal activity of PMNs against the HA-MRSA strain. HA-MRSA was the clinical strain with the highest ability to proliferate in the lungs and was accompanied by time-dependent up-regulation of rnaIII and hla.</p><p><bold>Conclusions</bold>: Our results provide novel evidence that the product of <italic>P. intermedia</italic> exerts a pathogenic effect on MRSA pneumonia, in particular with a strain exhibiting strong proliferation in the lower airway tract. Moreover, our results indicate that <italic>P. intermedia</italic> affects MRSA toxin expression <italic>via</italic> quorum sensing in a strain-dependent fashion, which might be important for understanding the pathogenesis of severe MRSA pneumonia.</p>