Pangenome comparison of Bacteroides fragilis genomospecies unveils genetic diversity and ecological insights

Author:

Oles Renee E.12ORCID,Carrillo Terrazas Marvic1ORCID,Loomis Luke R.1,Hsu Chia-Yun1ORCID,Tribelhorn Caitlin2,Belda-Ferre Pedro2ORCID,Ea Allison C.1,Bryant MacKenzie2ORCID,Young Jocelyn A.23ORCID,Carrow Hannah C.1ORCID,Sandborn William J.45,Dulai Parambir S.46,Sivagnanam Mamata23ORCID,Pride David1578,Knight Rob2591011ORCID,Chu Hiutung1512ORCID

Affiliation:

1. Department of Pathology, University of California, San Diego, California, USA

2. Department of Pediatrics, School of Medicine, University of California, San Diego, California, USA

3. Rady Children’s Hospital, San Diego, California, USA

4. Division of Gastroenterology, University of California, San Diego, California, USA

5. Center for Microbiome Innovation, University of California, San Diego, California, USA

6. Division of Gastroenterology, Northwestern University, Chicago, Illinois, USA

7. Center for Innovative Phage Applications and Therapeutics (IPATH), University of California, San Diego, California, USA

8. Center of Advanced Laboratory Medicine (CALM), University of California, San Diego, California, USA

9. Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, California, USA

10. Department of Computer Science & Engineering, University of California, San Diego, California, USA

11. Halıcıoğlu Data Science Institute, University of California, San Diego, California, USA

12. Chiba University-UC San Diego Center for Mucosal Immunology, Allergy and Vaccines (cMAV), University of California, San Diego, California, USA

Abstract

ABSTRACT Bacteroides fragilis is a Gram-negative commensal bacterium commonly found in the human colon, which differentiates into two genomospecies termed divisions I and II. Through a comprehensive collection of 694 B. fragilis whole genome sequences, we identify novel features distinguishing these divisions. Our study reveals a distinct geographic distribution with division I strains predominantly found in North America and division II strains in Asia. Additionally, division II strains are more frequently associated with bloodstream infections, suggesting a distinct pathogenic potential. We report differences between the two divisions in gene abundance related to metabolism, virulence, stress response, and colonization strategies. Notably, division II strains harbor more antimicrobial resistance (AMR) genes than division I strains. These findings offer new insights into the functional roles of division I and II strains, indicating specialized niches within the intestine and potential pathogenic roles in extraintestinal sites. IMPORTANCE Understanding the distinct functions of microbial species in the gut microbiome is crucial for deciphering their impact on human health. Classifying division II strains as Bacteroides fragilis can lead to erroneous associations, as researchers may mistakenly attribute characteristics observed in division II strains to the more extensively studied division I B. fragilis . Our findings underscore the necessity of recognizing these divisions as separate species with distinct functions. We unveil new findings of differential gene prevalence between division I and II strains in genes associated with intestinal colonization and survival strategies, potentially influencing their role as gut commensals and their pathogenicity in extraintestinal sites. Despite the significant niche overlap and colonization patterns between these groups, our study highlights the complex dynamics that govern strain distribution and behavior, emphasizing the need for a nuanced understanding of these microorganisms.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases

Publisher

American Society for Microbiology

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