Sulfated RaxX, which represents an unclassified group of ribosomally synthesized post-translationally modified peptides, binds a host immune receptor

Luu, D. D.; Joe, A.; Chen, Y.; Parys, K.; Bahar, O.; Pruitt, R.; Chen, L. J. G.; Petzold, C. J.; Long, K.; Adamchak, C.; Stewart, V.; Belkhadir, Y.; Ronald, P. C.

doi:10.1101/442517

bioRxiv · 10.1101/442517

Sulfated RaxX, which represents an unclassified group of ribosomally synthesized post-translationally modified peptides, binds a host immune receptor

Luu, D. D.·Joe, A.·Chen, Y.·Parys, K.·Bahar, O.·Pruitt, R.·Chen, L. J. G.·Petzold, C. J.·Long, K.·Adamchak, C.·Stewart, V.·Belkhadir, Y.·Ronald, P. C.

View original source ↗Export metadata ↓

Abstract

The rice immune receptor XA21 is activated by the sulfated microbial peptide RaxX (required for activation of XA21-mediated immunity X) produced by Xanthomonas oryzae pv. oryzae (Xoo). Mutational studies and targeted proteomics revealed that RaxX is processed and secreted by the protease/transporter RaxB, whose function can be partially fulfilled by a noncognate peptidase-containing transporter B (PctB). RaxX is cleaved at a Gly-Gly motif, yielding a mature peptide that retains the necessary elements for RaxX function as an immunogen and host peptide hormone mimic. These results indicate that RaxX is a founding member of a previously unclassified and understudied group of tyrosine sulfated RiPPs (ribosomally synthesized, post-translationally modified peptides). We further demonstrate that sulfated RaxX directly binds XA21 with high affinity. This work reveals a complete, previously uncharacterized biological process: bacterial RiPP biosynthesis, secretion, binding to a eukaryotic receptor and triggering of a robust host immune response.

Source connections

Published article ↗

Explore related subjects

microbiology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Luu, D. D., Joe, A., Chen, Y., Parys, K., Bahar, O., Pruitt, R., Chen, L. J. G., Petzold, C. J., Long, K., Adamchak, C., Stewart, V., Belkhadir, Y., Ronald, P. C.. 2018-10-13. Sulfated RaxX, which represents an unclassified group of ribosomally synthesized post-translationally modified peptides, binds a host immune receptor. https://doi.org/10.1101/442517

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Lipopolysaccharide and Wzi retain capsular polysaccharide at the Klebsiella pneumoniae cell surface and promote bloodstream infection fitness

Bacterial capsules are formed by individual capsular polysaccharide (CPS) polymers and are the outermost extracellular layers of many Gram-positive and Gram-negative bacteria. Capsules affect several aspects of bacterial biology, including resistance to host immune factors, survival in unfavorable environments and antimicrobial resistance. Research on CPS biology has largely focused on its synthesis and the pathogenic consequences of its presence or absence. Beyond synthesis, our understanding of its retention (attachment) on the cell surface is limited. Klebsiella pneumoniae is an important Gram-negative pathogen and expresses more than 80 capsular serotypes using the common Wzy-dependent CPS biosynthesis system and phenotypically manifests in various forms, making this species an attractive bacterial model to study the underexplored aspects of CPS biology. Here, we identified and characterized bacterial components involved in CPS retention in K. pneumoniae and assessed the importance of CPS retention on bloodstream fitness. Our examination revealed that lipopolysaccharide (LPS) and the outer-membrane protein, Wzi, collectively retain K. pneumoniae CPS on the bacterial surface. We demonstrate that the core-oligosaccharide domain of LPS and the extracellular surface of Wzi likely provide anchoring sites for CPS on the bacterial surface. Furthermore, CPS retention depends on divalent cation availability. Importantly, CPS retention on the bacterial surface is important for survival in serum and bacterial fitness at secondary infection sites in a murine bacteremia model. Together, our findings demonstrate that the functional importance of CPS to bacteria extends beyond synthesis and its overall abundance. Bacterial control over other CPS properties, like cell surface retention, are also important for K. pneumoniae fitness during bacteremia.

microbiology↗

bioRxiv2026

Systematic analysis reveals an Mln1-dependent trade-off between metabolic flexibility and thermotolerance in Cryptococcus neoformans

During infection, fungal pathogens must adapt to multiple environmental challenges, including changes in temperature, nutrient availability, and immune stress. Although transcriptional regulators are central to these adaptations, how individual regulators contribute to distinct environmental responses and how these responses are functionally interconnected remain poorly understood. Here, we investigated the functions of infection-associated transcription factors under distinct host-relevant conditions in Cryptococcus neoformans. Integrating in vivo expression profiling with infectivity data from signature-tagged mutagenesis, we prioritized 24 transcription factors, 12 of which were induced under host-mimicking conditions. Initial functional analyses revealed distinct roles for these transcription factors in adaptation to temperature, carbon, and nitrogen availability. Further characterization of Mln1, a fungal basic helix-loop-helix transcription factor, uncovered an unexpected connection between carbon source adaptation and thermotolerance. Mig1-dependent repression limited MLN1 expression in the presence of glucose, whereas Mln1 accumulated in the nucleus in the presence of trehalose or ethanol, but not glucose. Loss of MLN1 impaired carbon-starvation gene expression and growth on non-preferred carbon sources, particularly trehalose. Conversely, mln1{Delta} cells accumulated more intracellular trehalose and exhibited enhanced thermotolerance, yet showed reduced melanization, titan cell formation, virulence in Drosophila, and brain fungal burden in mice. Together, these results suggest that Mln1 contributes to metabolic flexibility and fungal virulence while differentially influencing thermotolerance. More broadly, these findings highlight a potential physiological trade-off between nutrient utilization and stress resistance, suggesting that these adaptive processes may be interconnected in fungal pathogens.

microbiology↗

bioRxiv2026

The large conjugative plasmid pAB3 integrates into the chromosome of Acinetobacter baumannii ATCC 17978

ATCC 17978 is one of the most utilised lab strains of Acinetobacter baumannii. Current literature suggests ATCC 17978 can have either a sulfamethoxazole-resistant phenotype or have the type VI secretion system (T6SS) switched on depending on the presence/absence of the large conjugative plasmid pAB3, which encodes the antimicrobial resistance gene (ARG) sul2 and T6SS repressors tetR1/tetR2. Here, we show that pAB3 integrates into the ATCC 17978 chromosome, which enables a large inversion resulting in the chromosomal arrangement labelled GS2.24 by Socru. This integration has no transcriptional impact on nearby genes or tetR1/tetR2. We find several instances were a portion of integrated pAB3 containing tetR2 is lost but the rest of the sequence, including sul2, is maintained, suggesting pAB3 integration may serve to make further rearrangements more tractable, enabling a putative T6SS+ sulfamethoxazole-resistant phenotype.

microbiology↗