Arpan De1, Weijie Chen2, Hao Li1, Justin R Wright3, Regina Lamendella4, Dana J Lukin5, Wendy A Szymczak6, Katherine Sun7, Libusha Kelly8, Subho Ghosh1, Daniel B Kearns9, Zhen He10, Christian Jobin10, Xiaoping Luo1, Arjun Byju1, Shirshendu Chatterjee11, Beng San Yeoh12, Matam Vijay-Kumar12, Jay X Tang13, Milankumar Prajapati14, Thomas B Bartnikas14, Sridhar Mani15. 1. Department of Medicine, Genetics and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York. 2. Department of Medicine, Genetics and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York; Department of Physics, Brown University, Providence, Rhode Island. 3. Wright Labs, LLC, Huntington, Pennsylvania. 4. Juniata College, Huntingdon, Pennsylvania. 5. Jill Roberts Center for Inflammatory Bowel Disease, New York, New York. 6. Department of Pathology, Montefiore Medical Center, Bronx, New York. 7. Department of Pathology, New York University Langone Health, New York, New York. 8. Department of Systems & Computational Biology, and Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York. 9. Department of Biology, Indiana University Bloomington, Bloomington, Indiana. 10. Department of Medicine, University of Florida, Gainesville, Florida. 11. Department of Mathematics, The City University of New York, City College & Graduate Center, New York, New York. 12. The University of Toledo-Microbiome Consortium, Department of Physiology & Pharmacology, University of Toledo, College of Medicine & Life Sciences, Toledo, Ohio. 13. Department of Physics, Brown University, Providence, Rhode Island. 14. Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island. 15. Department of Medicine, Genetics and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York. Electronic address: sridhar.mani@einsteinmed.org.
Abstract
BACKGROUND AND AIMS: Bacterial swarming, a collective movement on a surface, has rarely been associated with human pathophysiology. This study aims to define a role for bacterial swarmers in amelioration of intestinal stress. METHODS: We developed a polymicrobial plate agar assay to detect swarming and screened mice and humans with intestinal stress and inflammation. From chemically induced colitis in mice, as well as humans with inflammatory bowel disease, we developed techniques to isolate the dominant swarmers. We developed swarm-deficient but growth and swim-competent mutant bacteria as isogenic controls. We performed bacterial reinoculation studies in mice with colitis, fecal 16S, and meta-transcriptomic analyses, as well as in vitro microbial interaction studies. RESULTS: We show that bacterial swarmers are highly predictive of intestinal stress in mice and humans. We isolated a novel Enterobacter swarming strain, SM3, from mouse feces. SM3 and other known commensal swarmers, in contrast to their mutant strains, abrogated intestinal inflammation in mice. Treatment of colitic mice with SM3, but not its mutants, enriched beneficial fecal anaerobes belonging to the family of Bacteroidales S24-7. We observed SM3 swarming associated pathways in the in vivo fecal meta-transcriptomes. In vitro growth of S24-7 was enriched in presence of SM3 or its mutants; however, because SM3, but not mutants, induced S24-7 in vivo, we concluded that swarming plays an essential role in disseminating SM3 in vivo. CONCLUSIONS: Overall, our work identified a new but counterintuitive paradigm in which intestinal stress allows for the emergence of swarming bacteria; however, these bacteria act to heal intestinal inflammation.
BACKGROUND AND AIMS: Bacterial swarming, a collective movement on a surface, has rarely been associated with human pathophysiology. This study aims to define a role for bacterial swarmers in amelioration of intestinal stress. METHODS: We developed a polymicrobial plate agar assay to detect swarming and screened mice and humans with intestinal stress and inflammation. From chemically induced colitis in mice, as well as humans with inflammatory bowel disease, we developed techniques to isolate the dominant swarmers. We developed swarm-deficient but growth and swim-competent mutant bacteria as isogenic controls. We performed bacterial reinoculation studies in mice with colitis, fecal 16S, and meta-transcriptomic analyses, as well as in vitro microbial interaction studies. RESULTS: We show that bacterial swarmers are highly predictive of intestinal stress in mice and humans. We isolated a novel Enterobacter swarming strain, SM3, from mouse feces. SM3 and other known commensal swarmers, in contrast to their mutant strains, abrogated intestinal inflammation in mice. Treatment of colitic mice with SM3, but not its mutants, enriched beneficial fecal anaerobes belonging to the family of Bacteroidales S24-7. We observed SM3 swarming associated pathways in the in vivo fecal meta-transcriptomes. In vitro growth of S24-7 was enriched in presence of SM3 or its mutants; however, because SM3, but not mutants, induced S24-7 in vivo, we concluded that swarming plays an essential role in disseminating SM3 in vivo. CONCLUSIONS: Overall, our work identified a new but counterintuitive paradigm in which intestinal stress allows for the emergence of swarming bacteria; however, these bacteria act to heal intestinal inflammation.
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