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Enterococcus faecalis promotes innate immune suppression and polymicrobial catheter-associated urinary tract infection

Brenda Yin Qi Tien, Hwee Mian Sharon Goh, Kelvin Kian Long Chong, Soumili Bhaduri-Tagore, Sarah Holec, Regine Dress, Florent Ginhoux, Molly A. Ingersoll, Rohan B. H. Williams, Kimberly A. Kline
doi: https://doi.org/10.1101/133140
Brenda Yin Qi Tien
1Singapore Centre for Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore
2Singapore Centre for Environmental Life Sciences Engineering, Interdisciplinary Graduate School, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
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Hwee Mian Sharon Goh
1Singapore Centre for Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore
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Kelvin Kian Long Chong
1Singapore Centre for Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore
2Singapore Centre for Environmental Life Sciences Engineering, Interdisciplinary Graduate School, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
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Soumili Bhaduri-Tagore
1Singapore Centre for Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore
2Singapore Centre for Environmental Life Sciences Engineering, Interdisciplinary Graduate School, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551
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Sarah Holec
1Singapore Centre for Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore
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Regine Dress
4Singapore Immunology Network, Agency for Science, Technology, and Research (A*STAR), Singapore 138648, Singapore
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Florent Ginhoux
4Singapore Immunology Network, Agency for Science, Technology, and Research (A*STAR), Singapore 138648, Singapore
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Molly A. Ingersoll
5Unit of Dendritic Cell Immunobiology, Department of Immunology, Institut Pasteur, 75015 Paris, France
6INSERM U1223, Institut Pasteur, 75015 Paris, France
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Rohan B. H. Williams
3Singapore Centre for Environmental Life Sciences Engineering, National University of Singapore, Singapore
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Kimberly A. Kline
1Singapore Centre for Environmental Life Sciences Engineering, School of Biological Sciences, Nanyang Technological University, Singapore
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  • For correspondence: kkline@ntu.edu.sg
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Abstract

Enterococcus faecalis, a member of the human gastrointestinal microbiota, is an opportunistic pathogen associated with hospital-acquired wound, bloodstream, and urinary tract infections. E. faecalis can subvert or evade immune-mediated clearance, although the mechanisms are poorly understood. In this study, we examined E. faecalis-mediated subversion of macrophage activation. We observed that E. faecalis actively prevents NF-κB signaling in mouse RAW264.7 macrophages in the presence of Toll-like receptor agonists and during polymicrobial infection with Escherichia coli. E. faecalis and E. coli co-infection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared to E. coli infection alone. Finally, we demonstrated that co-inoculation of E. faecalis with E. coli into catheterized bladders significantly augmented E. coli CAUTI. Taken together, these results support that E. faecalis suppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis.

Author Summary Synergistic polymicrobial infections can contribute to both disease severity and persistence. Enterococcus faecalis and Escherichia coli are frequently co-isolated from polymicrobial urinary tract infections. Immunomodulation by co-infecting microbes can result in a more permissive environment for pathogens to establish infection. Presently, we do not yet understand how these microbes overcome host immunity to establish polymicrobial infections. To address this, we investigated how the immunosuppressive function of E. faecalis can contribute to acute infection. We defined that E. faecalis is able to suppress macrophages in vitro, despite the presence of E. coli. We also demonstrated E. faecalis’ ability to augment E. coli titers in vivo to establish kidney infection. Our findings raise the prospect that E. faecalis can alter host immunity to increase susceptibility to other uropathogens.

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Posted May 11, 2017.
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Enterococcus faecalis promotes innate immune suppression and polymicrobial catheter-associated urinary tract infection
Brenda Yin Qi Tien, Hwee Mian Sharon Goh, Kelvin Kian Long Chong, Soumili Bhaduri-Tagore, Sarah Holec, Regine Dress, Florent Ginhoux, Molly A. Ingersoll, Rohan B. H. Williams, Kimberly A. Kline
bioRxiv 133140; doi: https://doi.org/10.1101/133140
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Enterococcus faecalis promotes innate immune suppression and polymicrobial catheter-associated urinary tract infection
Brenda Yin Qi Tien, Hwee Mian Sharon Goh, Kelvin Kian Long Chong, Soumili Bhaduri-Tagore, Sarah Holec, Regine Dress, Florent Ginhoux, Molly A. Ingersoll, Rohan B. H. Williams, Kimberly A. Kline
bioRxiv 133140; doi: https://doi.org/10.1101/133140

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