Immunoglobulin A protease from Sutterella wadsworthensis modifies outcome of infection with Campylobacter jejuni and is associated with microbiome diversity

Sep 30, 2026

Uploaded by Jasmine

Sutterella wadsworthensis is linked to both healthy gut presence and certain gut diseases, including differences in therapeutic outcomes. This study reports a S. wadsworthensis subgroup encoding an IgA protease that cleaves human IgA1 and IgA2 but not mouse IgA. The protease activity affects Campylobacter jejuni infection outcomes in human epithelial cells and modulates phagocytosis in primary neutrophils. Comparative genomics and metagenomic screening associate this protease with global individuals and microbiome diversity, suggesting unique microbiota-derived IgA protease subsets with potential clinical relevance.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Background

Immunoglobulin A in mucosal immunity

IgA roles in gut homeostasis and infection susceptibility

Microbiota interactions with IgA proteases

GUT MICROBES 2026, VOL. 18, NO. 1, 2611543 [https://doi.org/10.1080/19490976.2025.261](https://doi.org/10.1080/19490976.2025.261)1543 RESEARCH ARTICLE Immunoglobulin A protease from Sutterella wadsworthensis modifies outcome of infection with Campylobacter jejuni and is associated with microbiome diversity Marwan E. Majzouba, 1, Fernando S. Santiagoa, 1, Shreeya S. Raicha, Prakruti Sirigeria, Isidora Simovica, b , Nicodemus Tedlaa and Nadeem O. Kaakousha aSchool of Biomedical Sciences, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia; bSchool of Biotechnology and Biomolecular Sciences, Faculty of Science, UNSW Sydney, Sydney, NSW, Australia ABSTRACT Sutterella wadsworthensis is an enigmatic member of the microbiota, previously reported to be present in healthy humans yet also associated with certain gut diseases and their therapeutic outcomes. Here, we report on S. wadsworthensis classified to S. wadsworthensis_A that encodes an immunoglobulin A (IgA) protease that digests human IgA1 and IgA2 but not mouse IgA. The activity of this IgA protease could influence the trajectory of Campylobacter jejuni infection in human epithelial cells and phagocytosis in primary neutrophils. Comparative genomics and screening of metagenomic samples revealed that the protease shared sequence identity with an IgA protease from a bacterium that colonized other mammals and that S. wadsworthensis harboring IgA protease can be detected in individuals globally. Individuals positive for S. wadsworthensis IgA protease in China and Fiji (detection at >90% similarity) were found to have a different microbiome when compared to individuals where the protease was not detected. Phylogenetic analysis of pathogen IgA proteases along with IgA proteases from members of the microbiota suggested that there may be a unique subset of microbiota-derived IgA proteases. Our results highlight the importance of taxonomic resolution in microbiome studies and identify a subgroup of S. wadsworthensis that may be of potential clinical relevance. ARTICLE HISTORY Received 30 October 2025 Revised 21 December 2025 Accepted 29 December 2025 KEYWORDS IgA-specific serine endopeptidases; microbiome; Sutterella; pathogenesis; metagenomics Background The production of antibodies is fundamental to a properly functioning immune system. Of the five classes, immunoglobulin A (IgA) is the most abundantly produced by far, with the majority localized at mucosal sites. Unlike circulating IgA that is produced by plasma cells in bone marrow as monomer (mIgA), mucosal IgA is produced by local plasma cells as a dimer (dIgA) . Humans produce two IgA subtypes, IgA1 and IgA2, the main difference being the lack of 13 amino acids from the hinge region of IgA2 . 1 IgA is best known for its capacity for immune exclusion, pathogen neutralization, and antigen excretion. In the gut, dIgA produced in the lamina propria is transported across the epithelium by poly Ig receptor and secreted to the lumen where it binds to bacteria or their products to stop their interaction with epithelial cells.2,3 Further, even prior to secretion, during transport through epithelial cells, IgA can bind intracellular bacteria or antigens and help shuttle them to the lumen.4 In the gut, IgA helps the immune system differentiate between commensals and pathogens by acting as a second signal that enables the conversion of pattern recognition receptor activation to inflammation. 1,5 IgA plays an influential role in susceptibility to microbial infections, and its role in other diseases has been revealed from data on IgA-deficient individuals. Despite many of these individuals having subclinical presentation, they have a significantly increased risk (up to ~10-fold) of developing chronic CONTACT Scientia A/Prof Nadeem O Kaakoush [n.kaakoush@unsw.edu.au](n.kaakoush@unsw.edu.au); Prof Nicodemus Tedla n.tedla@unsw.edu.au School of Biomedical Sciences, Faculty of Medicine and Healt

FAQs

What does the Sutterella wadsworthensis IgA protease do to human IgA subtypes?

It digests human IgA1 and IgA2 but not mouse IgA, based on the study’s reported specificity.

How is the IgA protease linked to Campylobacter jejuni infection?

The protease activity influences the trajectory of Campylobacter jejuni infection in human epithelial cells and affects phagocytosis in primary neutrophils.

What did comparative genomics and metagenomic screening reveal about detection and microbiome diversity?

The protease showed sequence identity with an IgA protease from bacteria colonizing other mammals, and it could be detected globally; individuals with detectable protease in China and Fiji showed different microbiome composition versus those without detection.

Sep 30, 2026

Uploaded by Jasmine