Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin Expression
Background: Methicillin-resistant Staphylococcus aureus (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...
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doaj-ed4e0d05f95940c2a3f6cc592e2510da2020-11-25T03:58:23ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-10-011110.3389/fmicb.2020.587235587235Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin ExpressionYu Yamashita0Kentaro Nagaoka1Hiroki Kimura2Masaru Suzuki3Tatsuya Fukumoto4Kasumi Hayasaka5Norihito Kaku6Yoshitomo Morinaga7Katsunori Yanagihara8Satoshi Konno9Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDivision of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, JapanDivision of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, JapanDepartment of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanBackground: Methicillin-resistant Staphylococcus aureus (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 Prevotella intermedia, a major periodontopathic pathogen, on MRSA pneumonia.Methods: The pathogenic effect of the supernatant of P. intermedia (Pi Sup) was investigated in a murine MRSA pneumonia model, using several clinical strains; whereas the bactericidal activity of polymorphonuclear leukocytes (PMNs) was investigated in vitro. 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 in vitro and in vivo.Results: 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). In vitro, 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.Conclusions: Our results provide novel evidence that the product of P. intermedia 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 P. intermedia affects MRSA toxin expression via quorum sensing in a strain-dependent fashion, which might be important for understanding the pathogenesis of severe MRSA pneumonia.https://www.frontiersin.org/article/10.3389/fmicb.2020.587235/fullmethicillin-resistant Staphylococcus aureuspneumoniamouse modelPrevotella intermediaquorum sensing system |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu Yamashita Kentaro Nagaoka Hiroki Kimura Masaru Suzuki Tatsuya Fukumoto Kasumi Hayasaka Norihito Kaku Yoshitomo Morinaga Katsunori Yanagihara Satoshi Konno |
spellingShingle |
Yu Yamashita Kentaro Nagaoka Hiroki Kimura Masaru Suzuki Tatsuya Fukumoto Kasumi Hayasaka Norihito Kaku Yoshitomo Morinaga Katsunori Yanagihara Satoshi Konno Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin Expression Frontiers in Microbiology methicillin-resistant Staphylococcus aureus pneumonia mouse model Prevotella intermedia quorum sensing system |
author_facet |
Yu Yamashita Kentaro Nagaoka Hiroki Kimura Masaru Suzuki Tatsuya Fukumoto Kasumi Hayasaka Norihito Kaku Yoshitomo Morinaga Katsunori Yanagihara Satoshi Konno |
author_sort |
Yu Yamashita |
title |
Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin Expression |
title_short |
Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin Expression |
title_full |
Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin Expression |
title_fullStr |
Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin Expression |
title_full_unstemmed |
Pathogenic Effect of Prevotella intermedia on a Mouse Pneumonia Model Due to Methicillin-Resistant Staphylococcus aureus With Up-Regulated α-Hemolysin Expression |
title_sort |
pathogenic effect of prevotella intermedia on a mouse pneumonia model due to methicillin-resistant staphylococcus aureus with up-regulated α-hemolysin expression |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Microbiology |
issn |
1664-302X |
publishDate |
2020-10-01 |
description |
Background: Methicillin-resistant Staphylococcus aureus (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 Prevotella intermedia, a major periodontopathic pathogen, on MRSA pneumonia.Methods: The pathogenic effect of the supernatant of P. intermedia (Pi Sup) was investigated in a murine MRSA pneumonia model, using several clinical strains; whereas the bactericidal activity of polymorphonuclear leukocytes (PMNs) was investigated in vitro. 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 in vitro and in vivo.Results: 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). In vitro, 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.Conclusions: Our results provide novel evidence that the product of P. intermedia 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 P. intermedia affects MRSA toxin expression via quorum sensing in a strain-dependent fashion, which might be important for understanding the pathogenesis of severe MRSA pneumonia. |
topic |
methicillin-resistant Staphylococcus aureus pneumonia mouse model Prevotella intermedia quorum sensing system |
url |
https://www.frontiersin.org/article/10.3389/fmicb.2020.587235/full |
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