{"id":11470,"date":"2016-09-14T16:43:25","date_gmt":"2016-09-14T19:43:25","guid":{"rendered":"https:\/\/www.infobioquimica.com\/new\/?p=11470"},"modified":"2016-09-14T16:43:25","modified_gmt":"2016-09-14T19:43:25","slug":"a-role-for-siderophores-in-klebsiella-pneumoniae-pathogenesis","status":"publish","type":"post","link":"https:\/\/www.infobioquimica.com\/new\/2016\/09\/14\/a-role-for-siderophores-in-klebsiella-pneumoniae-pathogenesis\/","title":{"rendered":"A role for siderophores in Klebsiella pneumoniae pathogenesis"},"content":{"rendered":"

The bacterium, estimated to be the third most common cause of hospital-acquired infections in the United States in a recent study<\/a>, can cause a wide range of infections such as pneumonia, bacteremia, wound or surgical site infections and urinary tract infections. What\u2019s more, Klebsiella pneumoniae<\/i><\/strong> is rapidly becoming resistant to all known antibiotics; resistant forms are considered an urgent threat to public health by the Centers for Disease Control and Prevention.<\/p>\n

What scientists have known about the organism is that it secretes small molecules called siderophores<\/strong> that enable it to acquire iron<\/strong> from a host and fuel its spread. Siderophores<\/strong> are thought to worsen infection<\/strong> by promoting bacterial growth. But a new study in mBio<\/i> this week demonstrates that siderophores do even more to help Klebsiella<\/i> invade.<\/p>\n

In mice infected with K. pneumoniae<\/i>, siderophores<\/strong> caused the animals to turn on proteins that increase inflammation and activated a master protein called HIF-1 alpha<\/strong> that paved the way for bacteria to spread from the lungs to the spleen. HIF-1 alpha<\/strong> controls the ability of substances to pass through blood vessels and inflammatory gene expression.<\/p>\n

\u201cWe\u2019ve known for a long time that siderophores are critical for bacteria to cause infection, because they steal iron from the host to grow,\u201d says senior study author Michael Bachman, M.D., Ph.D., assistant professor of clinical pathology and associate director of the Clinical Microbiology Laboratory at the University of Michigan in Ann Arbor. \u201cThis study sheds some light on the consequences of that. When the bacterium steals this iron, what\u2019s likely happening is the host cells are becoming stressed and are inducing inflammation and cell signaling pathways that actually worsen the infection by allowing the bacteria to escape from the lungs to the spleen.\u201d<\/p>\n

A barrier to studying siderophores in vivo in the past, Bachman says, is that they allow bacterial proliferation, which in turn may increase inflammation, tissue damage and bacterial dissemination. \u201cWhat we tried to do was control for levels of bacteria, and then compare infections in which the Klebsiella<\/i> made siderophores and in which it didn\u2019t,\u201d he explains. To study the effects of siderophore secretion independent of increased bacterial growth, Bachman\u2019s team employed tonB\u00a0<\/i>mutants<\/strong> capable of disrupting normal use of siderophores, so the organism could secrete siderophores but not use them.<\/p>\n

The investigators infected mice with either a strain of K. pneumoniae<\/i> that makes three siderophores called enterobactin (Ent), salmochelin (Sal) <\/strong>and yersiniabactin (Ybt)<\/strong>, or a mutant form of the bacterium that could not produce siderophores. Mice infected with the siderophore-producing strain had more bacteria invading from the lung to the spleen and they activated the cytokines IL-6, CXCL1<\/strong> and CXCL2.<\/strong><\/p>\n

\u201cWe had assumed that siderophores simply helped the bacteria grow more, triggering more inflammation and spread,\u201d Bachman says. \u201cNow we know siderophores can trigger these effects directly.\u201d<\/p>\n

Additional laboratory experiments in the mice revealed that all three siderophores were required for the most bacterial dissemination to the spleen; that siderophores secreted by K. pneumoniae <\/i>stabilized HIF-1 alpha; and that the presence of HIF-1 alpha in endothelial cells in the lungs is required for the bacteria to spread to the spleen. Mice that produced HIF-1 alpha and were infected with K. pneumoniae<\/i> had more bacterial invasion to the spleen than mice that did not produce HIF-1 alpha and were similarly infected.<\/p>\n

\u201cThese results indicate that bacterial siderophores directly alter the host response to pneumonia in addition to providing iron for bacterial growth,\u201d Bachman said. \u201cTherapies that disrupt production of siderophores could provide a two-pronged attack against K. pneumoniae<\/i> infection by preventing bacterial growth and preventing bacterial dissemination to the blood.\u201d<\/p>\n

Source:<\/strong> ASM<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

The bacterium, estimated to be the third most common cause of hospital-acquired infections in the United States in a recent study, can cause a wide range of infections such as pneumonia, bacteremia, wound or surgical site infections and urinary tract infections. What\u2019s more, Klebsiella pneumoniae is rapidly becoming resistant to all known antibiotics; resistant forms […]<\/p>\n","protected":false},"author":2620,"featured_media":11471,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"twitterCardType":"summary_large_image","cardImageID":0,"cardImage":"","cardTitle":"","cardDesc":"","cardImageAlt":"","cardPlayer":"","cardPlayerWidth":0,"cardPlayerHeight":0,"cardPlayerStream":"","cardPlayerCodec":"","footnotes":""},"categories":[655],"tags":[15023,15007,15019,15021,15011,15001,14995,15017,7799,15025,15005,15027,14993,15003,14991,15013,14999,15009,11265,14997,15015],"class_list":["post-11470","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticias-ingles","tag-bacteremia-en","tag-clinical-microbiology-laboratory","tag-cxcl1","tag-cxcl2","tag-enterobactin-ent","tag-hif-1-alpha","tag-hospital-acquired-infections","tag-il-6","tag-infection","tag-klebsiella-pneumoniae-en","tag-michael-bachman","tag-neumonia-en","tag-pathogenesis","tag-protein-hif-1-alpha","tag-public-health-risk","tag-salmochelin-sal","tag-siderophores","tag-university-of-michigan","tag-urinary-tract-infection-en","tag-urinary-tract-infections","tag-yersiniabactin-ybt"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/posts\/11470","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/users\/2620"}],"replies":[{"embeddable":true,"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/comments?post=11470"}],"version-history":[{"count":1,"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/posts\/11470\/revisions"}],"predecessor-version":[{"id":11472,"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/posts\/11470\/revisions\/11472"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/media\/11471"}],"wp:attachment":[{"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/media?parent=11470"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/categories?post=11470"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.infobioquimica.com\/new\/wp-json\/wp\/v2\/tags?post=11470"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}