Genome-Wide Analysis of Antigen 43 (Ag43) Variants: New Insights in Their Diversity, Distribution and Prevalence in Bacteria
Antigen 43 (Ag43) expression induces aggregation and biofilm formation that has consequences for bacterial colonisation and infection. Ag43 is secreted through the Type 5 subtype “a” secretion system (T5aSS) and is a prototypical member of the family of self-associating autotransporters (SAATs). As...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/6/5500 |
| Summary: | Antigen 43 (Ag43) expression induces aggregation and biofilm formation that has consequences for bacterial colonisation and infection. Ag43 is secreted through the Type 5 subtype “a” secretion system (T5aSS) and is a prototypical member of the family of self-associating autotransporters (SAATs). As a T5aSS protein, Ag43 has a modular architecture comprised of (i) a signal peptide, (ii) a passenger domain that can be subdivided into three subdomains (SL, EJ, and BL), (iii) an autochaperone (AC) domain, and (iv) an outer membrane translocator. The cell-surface SL subdomain is directly involved in the “Velcro-handshake” mechanism resulting in bacterial autoaggregation. Ag43 is considered to have a ubiquitous distribution in <i>E. coli</i> genomes and many strains harbour multiple <i>agn43</i> genes. However, recent phylogenetic analyses indicated the existence of four distinct Ag43 classes exhibiting different propensities for autoaggregation and interactions. Given the knowledge of the diversity and distribution of Ag43 in <i>E. coli</i> genomes is incomplete, we have performed a thorough in silico investigation across bacterial genomes. Our comprehensive analyses indicate that Ag43 passenger domains cluster in six phylogenetic classes associated with different SL subdomains. The diversity of Ag43 passenger domains is a result of the association of the SL subtypes with two different EJ-BL-AC modules. We reveal that <i>agn43</i> is almost exclusively present among bacterial species of the Enterobacteriaceae family and essentially in the <i>Escherichia</i> genus (99.6%) but that it is not ubiquitous in <i>E. coli</i>. The gene is typically present as a single copy but up to five copies of <i>agn43</i> with different combinations of classes can be observed. The presence of <i>agn43</i> as well as its different classes appeared to differ between <i>Escherichia</i> phylogroups. Strikingly, <i>agn43</i> is present in 90% of <i>E. coli</i> from E phylogroup. Our results shed light on Ag43 diversity and provide a rational framework for investigating its role in <i>E. coli</i> ecophysiology and physiopathology. |
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| ISSN: | 1661-6596 1422-0067 |