{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:02:46Z","timestamp":1768518166430,"version":"3.49.0"},"posted":{"date-parts":[[2024,10,11]]},"group-title":"Microbiology","reference-count":103,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Many species of pathogenic bacteria harbor critical plasmid-encoded virulence factors, and yet the regulation of plasmid replication is often poorly understood despite playing a critical role in plasmid-encoded gene expression. Human pathogenic\n                  <jats:italic>Yersinia<\/jats:italic>\n                  , including the plague agent\n                  <jats:italic>Y. pestis<\/jats:italic>\n                  and its close relative\n                  <jats:italic>Y. pseudotuberculosis<\/jats:italic>\n                  , require the type III secretion system (T3SS) virulence factor to subvert host defense mechanisms and colonize host tissues. The\n                  <jats:italic>Yersinia<\/jats:italic>\n                  T3SS is encoded on the IncFII\n                  <jats:underline>p<\/jats:underline>\n                  lasmid for\n                  <jats:italic>\n                    <jats:underline>Y<\/jats:underline>\n                    ersinia\n                  <\/jats:italic>\n                  <jats:underline>v<\/jats:underline>\n                  irulence (pYV). Several layers of gene regulation enables a large increase in expression of\n                  <jats:italic>Yersinia<\/jats:italic>\n                  T3SS genes at mammalian body temperature. Surprisingly, T3SS expression is also controlled at the level of gene dosage. The number of pYV molecules relative to the number of chromosomes per cell, referred to as plasmid copy number, increases with temperature. The ability to increase and maintain elevated pYV plasmid copy number, and therefore T3SS gene dosage, at 37\u00b0C is important for\n                  <jats:italic>Yersinia<\/jats:italic>\n                  virulence. In addition, pYV is highly stable in\n                  <jats:italic>Yersinia<\/jats:italic>\n                  at all temperatures, despite being dispensable for growth outside the host. Yet how\n                  <jats:italic>Yersinia<\/jats:italic>\n                  reinforces elevated plasmid replication and plasmid stability remains unclear. In this study, we show that the chromosomal gene\n                  <jats:italic>pcnB<\/jats:italic>\n                  encoding the polyadenylase PAP I is required for regulation of pYV plasmid copy number (PCN), maintenance of pYV in the bacterial population outside the host, robust T3SS activity, and\n                  <jats:italic>Yersinia<\/jats:italic>\n                  virulence in a mouse infection model. Likewise,\n                  <jats:italic>pcnB<\/jats:italic>\n                  \/PAP I is also required for robust expression of the\n                  <jats:italic>Shigella flexneri<\/jats:italic>\n                  virulence plasmid-encoded T3SS. Furthermore,\n                  <jats:italic>Yersinia<\/jats:italic>\n                  and\n                  <jats:italic>Shigella pcnB<\/jats:italic>\n                  \/PAP I is required for maintaining normal PCN of model antimicrobial resistance (AMR) plasmids whose replication is regulated by sRNA, thereby increasing antibiotic resistance by ten-fold. These data suggest that\n                  <jats:italic>pcnB<\/jats:italic>\n                  \/PAP I contributes to the spread and stabilization of virulence and AMR plasmids in bacterial pathogens, and is essential in maintaining the gene dosage required to mediate plasmid-encoded traits. Importantly\n                  <jats:italic>pcnB<\/jats:italic>\n                  \/PAP I has been bioinformatically identified in many species of bacteria despite being studied in only a few species to date. Our work highlights the potential importance of\n                  <jats:italic>pcnB<\/jats:italic>\n                  \/PAP I in antibiotic resistance, and shows for the first time that\n                  <jats:italic>pcnB<\/jats:italic>\n                  \/PAP I reinforces PCN and virulence plasmid stability in natural pathogenic hosts with a direct impact on bacterial virulence.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Author Summary<\/jats:title>\n                  <jats:p>\n                    Many pathogens carry extrachromosomal DNA elements known as plasmids, which encode genes that confer bacterial virulence or antimicrobial resistance (AMR). Acquisition of these plasmids by bacteria can lead to the emergence of new pathogenic traits and the spread of AMR, yet the mechanisms by which plasmids are retained in bacterial populations particularly in the absence of selective pressure remain incompletely understood. Here we show that the major bacterial polyadenylase enzyme PAP I, encoded by the\n                    <jats:italic>pcnB<\/jats:italic>\n                    gene, is critical for the human pathogen\n                    <jats:italic>Yersinia pseudotuberculosis<\/jats:italic>\n                    to maintain its native virulence plasmid as well as AMR plasmids. Very little is known about the process of polyadenylation in bacteria, or the post-transcriptional addition of adenosine residues to the 3\u2019 end of transcripts. This study represents the first demonstration that PAP I-mediated polyadenylation contributes to bacterial pathogenesis.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.10.11.617751","type":"posted-content","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T23:35:11Z","timestamp":1728689711000},"source":"Crossref","is-referenced-by-count":1,"title":["The polyadenylase PAPI is required for virulence plasmid maintenance in pathogenic bacteria"],"prefix":"10.64898","author":[{"given":"Katherine","family":"Schubert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micah","family":"Braly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele 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