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Biofilm formation in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Y<\/jats:italic>\n                    <\/jats:styled-content>\n                    .\n                    <jats:italic>\u2009pestis<\/jats:italic>\n                    is controlled by the intracellular levels of the second messenger molecule cyclic diguanylate (\n                    <jats:styled-content style=\"fixed-case\">c<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">di<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">GMP<\/jats:styled-content>\n                    ).\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:roman>HmsT<\/jats:roman>\n                    <\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">Y<\/jats:styled-content>\n                    3730, the two diguanylate cyclases (DGC) in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Y<\/jats:italic>\n                    <\/jats:styled-content>\n                    .\n                    <jats:italic>\u2009pestis<\/jats:italic>\n                    , are responsible for the synthesis of\n                    <jats:styled-content style=\"fixed-case\">c<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">di<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">GMP<\/jats:styled-content>\n                    .\n                    <jats:styled-content style=\"fixed-case\">Y<\/jats:styled-content>\n                    3730, which we name here as\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:roman>HmsD<\/jats:roman>\n                    <\/jats:styled-content>\n                    , has little effect on\n                    <jats:italic>in vitro<\/jats:italic>\n                    biofilms, but has a major effect on biofilm formation in the flea. The mechanism by which\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:roman>HmsD<\/jats:roman>\n                    <\/jats:styled-content>\n                    plays differential roles\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    is not understood. In this study, we show that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>hmsD<\/jats:italic>\n                    <\/jats:styled-content>\n                    is part of a three\u2010gene operon (\n                    <jats:styled-content style=\"fixed-case\">y<\/jats:styled-content>\n                    3729\u201031), which we designate as\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>hmsCDE<\/jats:italic>\n                    <\/jats:styled-content>\n                    . Deletion of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>hmsC<\/jats:italic>\n                    <\/jats:styled-content>\n                    resulted in increased,\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>hmsD<\/jats:italic>\n                    <\/jats:styled-content>\n                    \u2010dependent biofilm formation, while deletion or overexpression of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>hmsE<\/jats:italic>\n                    <\/jats:styled-content>\n                    did not affect biofilm formation. Localization experiments suggest that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:roman>HmsC<\/jats:roman>\n                    <\/jats:styled-content>\n                    resides in the periplasmic space. In addition, we provide evidence that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:roman>HmsC<\/jats:roman>\n                    <\/jats:styled-content>\n                    might interact directly with the periplasmic domain of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:roman>HmsD<\/jats:roman>\n                    <\/jats:styled-content>\n                    and cause the proteolysis of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:roman>HmsD<\/jats:roman>\n                    <\/jats:styled-content>\n                    . We propose that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:roman>HmsC<\/jats:roman>\n                    <\/jats:styled-content>\n                    senses the environmental signals, which in turn regulates\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:roman>HmsD<\/jats:roman>\n                    <\/jats:styled-content>\n                    , and controls the\n                    <jats:styled-content style=\"fixed-case\">c<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">di<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">GMP<\/jats:styled-content>\n                    synthesis and biofilm formation in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Y<\/jats:italic>\n                    <\/jats:styled-content>\n                    <jats:italic>.\u2009pestis<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/1462-2920.12323","type":"journal-article","created":{"date-parts":[[2013,11,5]],"date-time":"2013-11-05T23:43:10Z","timestamp":1383694990000},"page":"1202-1216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["<scp>\n                      <scp>HmsC<\/scp>\n                    <\/scp>\n                    , a periplasmic protein, controls biofilm formation via repression of\n                    <scp>\n                      <scp>HmsD<\/scp>\n                    <\/scp>\n                    , a diguanylate cyclase in\n                    <scp>\n                      <i>Y<\/i>\n                    <\/scp>\n                    <i>ersinia 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