{
  "abstract": "Pseudomonas aeruginosa is an opportunistic human pathogen capable of infecting a wide range of tissues and organs. Its persistence during chronic infection is strongly associated with biofilm formation, which depends on extracellular polysaccharides such as alginate. The HtrA-like periplasmic serine protease MucD is a key regulator of bacterial virulence, stress response, and alginate production, yet its molecular mechanism has remained largely unclear. Here, we discovered the alginate acetylation and export proteins AlgX and AlgK as MucD substrates, and characterized their degradation by mass spectrometry and bioinformatic analysis. We further determined the cryo-EM structure of MucD bound to an AlgK-derived substrate peptide, offering atomic insights into MucD oligomerization assembly, substrate recognition, and specificity. Together with structure-guided mutagenesis and biochemical assays, our results revealed that MucD proteolytic activity is governed by an equilibrium between a resting 12-mer and an active trimer. Crucially, we demonstrate that MucD represses alginate biosynthesis post-translationally, in addition to its previously implicated role in transcriptional regulation. These findings define a distinct activation mechanism and regulatory function for MucD and provide new insight into bacterial HtrA-like serine proteases.\n\nThe persistence of Pseudomonas aeruginosa during chronic infection relies on alginate production, a process regulated by the serine protease MucD. This study identifies the alginate acetylation and export proteins AlgX and AlgK as MucD substrates and shows that MucD proteolytic activity is regulated by oligomerization.",
  "abstract_shown": true,
  "affiliations": [
    "School of Biological Sciences, Nanyang Technological University, Singapore, Singapore",
    "NTU Institute of Structural Biology, Nanyang Technological University, Singapore, Singapore"
  ],
  "article_type": "Short Reports",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yujun Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xin-Fu Yan"
    },
    {
      "name": "Rya Ero"
    },
    {
      "name": "Chao Wang"
    },
    {
      "name": "Kanaga Sabapathy"
    },
    {
      "name": "Yong-Gui Gao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/adf10nmkptfne.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pbio.3003985",
  "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003985",
  "id": "adf10nmkptfne",
  "issns": [
    "1545-7885"
  ],
  "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003985",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Bacterial biofilms and quorum sensing"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Biosynthesis"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Enzymology/Enzymes/Proteases"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Metabolism/Metabolic processes/Proteolysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Enzymes/Proteases"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Proteolysis"
    ],
    [
      "plos",
      "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens/Pseudomonas aeruginosa"
    ],
    [
      "plos",
      "/Biology and life sciences/Organisms/Bacteria/Pseudomonas/Pseudomonas aeruginosa"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens/Pseudomonas aeruginosa"
    ],
    [
      "plos",
      "/Physical sciences/Materials science/Materials/Oligomers"
    ],
    [
      "plos",
      "/Research and analysis methods/Database and informatics methods/Bioinformatics/Sequence analysis/Sequence alignment"
    ],
    [
      "plos",
      "/Research and analysis methods/Microscopy/Electron microscopy/Electron cryo-microscopy"
    ],
    [
      "plos",
      "/Research and analysis methods/Separation processes/Filtration/Gel filtration"
    ]
  ],
  "openalex": "W7213919084",
  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003985&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/adf10nmkptfne.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pbio.3003985",
      "source": "plos",
      "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003985"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:enzymology",
      "subfield": "enzymology-metabolism"
    },
    {
      "field": "biology",
      "origin": "plos:microbiology",
      "subfield": "microbiology"
    },
    {
      "field": "chemistry",
      "origin": "plos:materials science",
      "subfield": "materials-polymers"
    }
  ],
  "title": "MucD regulates alginate biosynthesis through the proteolytic control of AlgX and AlgK in Pseudomonas aeruginosa",
  "title_text": "MucD regulates alginate biosynthesis through the proteolytic control of AlgX and AlgK in Pseudomonas aeruginosa",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/adf10nmkptfne",
  "venue": "PLOS Biology",
  "versions": [
    {
      "doi": "10.64898/2026.08.29.748010",
      "pid": "7re67vetyat68",
      "relation": "preprint",
      "title": "MucD regulates alginate biosynthesis through the proteolytic control of AlgX and AlgK in Pseudomonas aeruginosa",
      "venue": "bioRxiv"
    }
  ]
}