{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:21:06Z","timestamp":1790047266148,"version":"4.0.1"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2014,2,11]],"date-time":"2014-02-11T00:00:00Z","timestamp":1392076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,2,28]],"date-time":"2014-02-28T00:00:00Z","timestamp":1393545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,2,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            To adapt to stresses encountered in stationary phase, Gram-negative bacteria utilize the alternative sigma factor RpoS. However, some species lack RpoS; thus, it is unclear how stationary-phase adaptation is regulated in these organisms. Here we defined the growth-phase-dependent transcriptomes of\n            <jats:named-content content-type=\"genus-species\">Haemophilus ducreyi<\/jats:named-content>\n            , which lacks an RpoS homolog. Compared to mid-log-phase organisms, cells harvested from the stationary phase upregulated genes encoding several virulence determinants and a homolog of\n            <jats:italic>hfq<\/jats:italic>\n            . Insertional inactivation of\n            <jats:italic>hfq<\/jats:italic>\n            altered the expression of ~16% of the\n            <jats:named-content content-type=\"genus-species\">H. ducreyi<\/jats:named-content>\n            genes. Importantly, there were a significant overlap and an inverse correlation in the transcript levels of genes differentially expressed in the\n            <jats:italic>hfq<\/jats:italic>\n            inactivation mutant relative to its parent and the genes differentially expressed in stationary phase relative to mid-log phase in the parent. Inactivation of\n            <jats:italic>hfq<\/jats:italic>\n            downregulated genes in the\n            <jats:italic>flp-tad<\/jats:italic>\n            and\n            <jats:italic>lspB-lspA2<\/jats:italic>\n            operons, which encode several virulence determinants. To comply with FDA guidelines for human inoculation experiments, an unmarked\n            <jats:italic>hfq<\/jats:italic>\n            deletion mutant was constructed and was fully attenuated for virulence in humans. Inactivation or deletion of\n            <jats:italic>hfq<\/jats:italic>\n            downregulated Flp1 and impaired the ability of\n            <jats:named-content content-type=\"genus-species\">H. ducreyi<\/jats:named-content>\n            to form microcolonies, downregulated DsrA and rendered\n            <jats:named-content content-type=\"genus-species\">H. ducreyi<\/jats:named-content>\n            serum susceptible, and downregulated LspB and LspA2, which allow\n            <jats:named-content content-type=\"genus-species\">H. ducreyi<\/jats:named-content>\n            to resist phagocytosis. We propose that, in the absence of an RpoS homolog, Hfq serves as a major contributor of\n            <jats:named-content content-type=\"genus-species\">H. ducreyi<\/jats:named-content>\n            stationary-phase and virulence gene regulation. The contribution of Hfq to stationary-phase gene regulation may have broad implications for other organisms that lack an RpoS homolog.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Pathogenic bacteria encounter a wide range of stresses in their hosts, including nutrient limitation; the ability to sense and respond to such stresses is crucial for bacterial pathogens to successfully establish an infection. Gram-negative bacteria frequently utilize the alternative sigma factor RpoS to adapt to stresses and stationary phase. However, homologs of RpoS are absent in some bacterial pathogens, including\n            <jats:named-content content-type=\"genus-species\">Haemophilus ducreyi<\/jats:named-content>\n            , which causes chancroid and facilitates the acquisition and transmission of HIV-1. Here, we provide evidence that, in the absence of an RpoS homolog, Hfq serves as a major contributor of stationary-phase gene regulation and that Hfq is required for\n            <jats:named-content content-type=\"genus-species\">H. ducreyi<\/jats:named-content>\n            to infect humans. To our knowledge, this is the first study describing Hfq as a major contributor of stationary-phase gene regulation in bacteria and the requirement of Hfq for the virulence of a bacterial pathogen in humans.\n          <\/jats:p>","DOI":"10.1128\/mbio.01081-13","type":"journal-article","created":{"date-parts":[[2014,2,12]],"date-time":"2014-02-12T02:34:41Z","timestamp":1392172481000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["Haemophilus ducreyi Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase"],"prefix":"10.1128","volume":"5","author":[{"given":"Dharanesh","family":"Gangaiah","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Labandeira-Rey","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate R.","family":"Fortney","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Ellinger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Zwickl","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Baker","sequence":"additional","affiliation":[{"name":"Center for Microbial Pathogenesis, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M.","family":"Janowicz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry P.","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad A.","family":"Brautigam","sequence":"additional","affiliation":[{"name":"Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Robert S.","family":"Munson","sequence":"additional","affiliation":[{"name":"Center for Microbial Pathogenesis, Nationwide Children\u2019s Hospital, Columbus, Ohio, USA"},{"name":"Department of Pediatrics, the Ohio State University College of Medicine, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, 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