{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:36:06Z","timestamp":1792672566604,"version":"4.5.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T00:00:00Z","timestamp":1478563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,12,30]],"date-time":"2016-12-30T00:00:00Z","timestamp":1483056000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000185","name":"DOD | Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["W911NF-15-2-0036"],"award-info":[{"award-number":["W911NF-15-2-0036"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,12,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content content-type=\"genus-species\">Bdellovibrio bacteriovorus<\/jats:named-content>and<jats:named-content content-type=\"genus-species\">Micavibrio aeruginosavorus<\/jats:named-content>are predatory bacteria that naturally\u2014and obligately\u2014prey on other Gram-negative bacteria, and their use has been proposed as a potential new approach to control microbial infection. The ability of predatory bacteria to prey on Gram-negative human pathogens<jats:italic>in vitro<\/jats:italic>is well documented; however, the<jats:italic>in vivo<\/jats:italic>safety and efficacy of predatory bacteria have yet to be fully assessed. In this study, we examined whether predatory bacteria can reduce bacterial burden in the lungs in an<jats:italic>in vivo<\/jats:italic>mammalian system. Initial safety studies were performed by intranasal inoculation of rats with predatory bacteria. No adverse effects or lung pathology were observed in rats exposed to high concentrations of predatory bacteria at up to 10\u00a0days postinoculation. Enzyme-linked immunosorbent assay (ELISA) of the immune response revealed a slight increase in inflammatory cytokine levels at 1\u00a0h postinoculation that was not sustained by 48\u00a0h. Additionally, dissemination experiments showed that predators were efficiently cleared from the host by 10 days postinoculation. To measure the ability of predatory bacteria to reduce microbial burden<jats:italic>in vivo<\/jats:italic>, we introduced sublethal concentrations of<jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>into the lungs of rats via intranasal inoculation and followed with multiple doses of predatory bacteria over 24\u00a0h. Predatory bacteria were able to reduce<jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>bacterial burden, on average, by more than 3.0 log<jats:sub>10<\/jats:sub>in the lungs of most rats as measured by CFU plating. The work presented here provides further support for the idea of developing predatory bacteria as a novel biocontrol agent.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>A widely held notion is that antibiotics are the greatest medical advance of the last 50\u00a0years. However, the rise of multidrug-resistant (MDR) bacterial infections has become a global health crisis over the last decade. As we enter the postantibiotic era, it is crucial that we begin to develop new strategies to combat bacterial infection. Here, we report one such new approach: the use of predatory bacteria (<jats:named-content content-type=\"genus-species\">Bdellovibrio bacteriovorus<\/jats:named-content>and<jats:named-content content-type=\"genus-species\">Micavibrio aeruginosavorus<\/jats:named-content>) that naturally\u2014and obligately\u2014prey on other Gram-negative bacteria. To our knowledge, this is the first study that demonstrated the ability of predatory bacteria to attenuate the bacterial burden of a key human pathogen in an<jats:italic>in vivo<\/jats:italic>mammalian system. As the prevalence of MDR infections continues to rise each year, our results may represent a shift in how we approach treating microbial infections in the future.<\/jats:p>","DOI":"10.1128\/mbio.01847-16","type":"journal-article","created":{"date-parts":[[2016,11,9]],"date-time":"2016-11-09T11:00:34Z","timestamp":1478689234000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":110,"title":["Predatory Bacteria Attenuate Klebsiella pneumoniae Burden in Rat Lungs"],"prefix":"10.1128","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1603-5326","authenticated-orcid":false,"given":"Kenneth","family":"Shatzkes","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Singleton","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Zuena","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Shukla","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpi","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Dharani","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onoyom","family":"Onyile","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Rinaggio","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy D.","family":"Connell","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Kadouri","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"226","article-title":"On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae","volume":"10","author":"Fleming A","year":"1929","unstructured":"Fleming A. 1929. 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