Contributions of Streptococcus mutans Cnm and PA antigens to aggravation of non-alcoholic steatohepatitis in mice.

Shuhei Naka,Kazuhiko Nakano,Rina Hatakeyama,Ryota Nomura,Yukiko Takashima,Michiyo Matsumoto-Nakano

doi:10.1038/srep36886

Shuhei Naka, Kazuhiko Nakano + Show 4 more

Open Access

https://doi.org/10.1038/srep36886

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Journal: Scientific Reports	Publication Date: Nov 11, 2016
Citations: 27	License type: CC BY 4.0

Affiliation: Osaka University, Okayama University

Abstract

Streptococcus mutans, a major pathogen of dental caries, can cause infective endocarditis after invading the bloodstream. Recently, intravenous administration of specific S. mutans strains was shown to aggravate non-alcoholic steatohepatitis (NASH) in a mouse model fed a high-fat diet. Here, we investigated the mechanism of this aggravation in a NASH mouse model by focusing on the S. mutans cell surface collagen-binding protein (Cnm) and the 190-kDa protein antigen (PA). Mice that were intravenously administered a S. mutans strain with a defect in Cnm (TW871CND) or PA (TW871PD) did not show clinical or histopathological signs of NASH aggravation, in contrast to those administered the parent strain TW871. The immunochemical analyses demonstrated higher levels of interferon-γ and metallothionein expression in the TW871 group than in the TW871CND and TW871PD groups. Analysis of bacterial affinity to cultured hepatic cells in the presence of unsaturated fatty acids revealed that the incorporation rate of TW871 was significantly higher than those of TW871CND and TW871PD. Together, our results suggest that Cnm and PA are important cell surface proteins for the NASH aggravation caused by S. mutans adhesion and affinity for hepatic cells.

Highlights

Mainly used in the cellular hydrophobicity assays that are commonly performed for studying the virulence of dental caries caused by S. mutans[15]
We previously reported that intravenous administration of S. mutans TW871 aggravates non-alcoholic steatohepatitis (NASH) conditions[7], though the relevant mechanism remained to be elucidated
The TW871 that had been treated with formalin did not induce NASH aggravation (Fig. S3), suggesting that viable cells may be crucial for the NASH aggravation caused by S. mutans TW871

Summary

Introduction

Mainly used in the cellular hydrophobicity assays that are commonly performed for studying the virulence of dental caries caused by S. mutans[15]. The association between saturated and/or unsaturated fatty acids and NASH aggravation remains to be elucidated Based on these factors, we hypothesised that Cnm+/PA+ S. mutans strains could incorporate into liver tissues that had accumulated fatty acids, leading to the aggravation of NASH. We hypothesised that Cnm+/PA+ S. mutans strains could incorporate into liver tissues that had accumulated fatty acids, leading to the aggravation of NASH To examine this possible mechanism of S. mutans-associated aggravation of NASH, we assessed the NASH aggravation in a NASH mouse model following the administration of Cnm- or PA-defective isogenic mutant strains or their complemented mutant strains. The affinity of bacterial cells for various fatty acids was evaluated using protocols based on cellular hydrophobicity assays and focusing on the S. mutans bacterial cell surface antigens Cnm and PA. We investigated the interaction of bacterial cells with various types of fatty acids using cultured hepatic cells to evaluate differences in their fat accumulation

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