Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Protect from Infection
ABSTRACT Carbapenem-resistant (CR) sequence type 258 (ST258) Klebsiella pneumoniae has become an urgent health care threat, causing an increasing number of high-mortality infections. Its resistance to numerous antibiotics and threat to immunocompromised patients necessitate finding new therapies to...
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2018-05-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00091-18 |
| _version_ | 1818740163619061760 |
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| author | Elizabeth Diago-Navarro Michael P. Motley Gonzalo Ruiz-Peréz Winnie Yu Julianne Austin Bruna M. S. Seco Guozhi Xiao Aniska Chikhalya Peter H. Seeberger Bettina C. Fries |
| author_facet | Elizabeth Diago-Navarro Michael P. Motley Gonzalo Ruiz-Peréz Winnie Yu Julianne Austin Bruna M. S. Seco Guozhi Xiao Aniska Chikhalya Peter H. Seeberger Bettina C. Fries |
| author_sort | Elizabeth Diago-Navarro |
| collection | DOAJ |
| description | ABSTRACT Carbapenem-resistant (CR) sequence type 258 (ST258) Klebsiella pneumoniae has become an urgent health care threat, causing an increasing number of high-mortality infections. Its resistance to numerous antibiotics and threat to immunocompromised patients necessitate finding new therapies to combat these infections. Previous successes in the laboratory, as well as the conservation of capsular polysaccharide (CPS) among the members of the ST258 clone, suggest that monoclonal antibody (MAb) therapy targeting the outer polysaccharide capsule of K. pneumoniae could serve as a valuable treatment alternative for afflicted patients. Here, we isolated several IgG antibodies from mice inoculated with a mixture of CR K. pneumoniae CPS conjugated to anthrax protective antigen. Two of these MAbs, 17H12 and 8F12, bind whole and oligosaccharide epitopes of the CPS of clade 2 ST258 CR K. pneumoniae, which is responsible for the most virulent CR K. pneumoniae infections in the United States. These antibodies were shown to agglutinate all clade 2 strains and were also shown to promote extracellular processes killing these bacteria, including biofilm inhibition, complement deposition, and deployment of neutrophil extracellular traps. Additionally, they promoted opsonophagocytosis and intracellular killing of CR K. pneumoniae by human-derived neutrophils and cultured murine macrophages. Finally, when mice were intratracheally infected with preopsonized clade 2 CR K. pneumoniae, these MAbs reduced bacterial dissemination to organs. Our data suggest that broadly reactive anticapsular antibodies and vaccines against clade 2 ST258 CR K. pneumoniae are possible. Such MAbs and vaccines would benefit those susceptible populations at risk of infection with this group of multidrug-resistant bacteria. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is an enteric bacterium that has been responsible for an increasing number of deadly outbreaks and hospital-acquired infections. The pathogen’s resistance to numerous antibiotics, including new drugs, leaves few therapeutic options available for infected patients, who often are too sick to fight the infection themselves. Immunotherapy utilizing monoclonal antibodies has been successful in other medical fields, and antibodies targeting the outer polysaccharide capsule of these bacteria could be a valuable treatment alternative. This study presents two anticapsular antibodies, 17H12 and 8F12, that were found to be protective against the most virulent carbapenem-resistant K. pneumoniae clinical strains. These antibodies are shown to promote the killing of these strains through several extracellular and intracellular processes and prevent the spread of infection in mice from the lungs to distal organs. Thus, they could ultimately treat or protect patients infected or at risk of infection by this multidrug-resistant bacterium. |
| first_indexed | 2024-12-18T01:36:22Z |
| format | Article |
| id | doaj.art-475d1bdb95ea44b7bba56568533382fa |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-18T01:36:22Z |
| publishDate | 2018-05-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-475d1bdb95ea44b7bba56568533382fa2022-12-21T21:25:26ZengAmerican Society for MicrobiologymBio2150-75112018-05-019210.1128/mBio.00091-18Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Protect from InfectionElizabeth Diago-Navarro0Michael P. Motley1Gonzalo Ruiz-Peréz2Winnie Yu3Julianne Austin4Bruna M. S. Seco5Guozhi Xiao6Aniska Chikhalya7Peter H. Seeberger8Bettina C. Fries9Department of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, USADepartment of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, USAUniversidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, SpainDepartment of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, USADepartment of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, USADepartment of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, GermanyDepartment of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, GermanyDepartment of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USADepartment of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, GermanyDepartment of Medicine, Infectious Disease Division, Stony Brook University, Stony Brook, New York, USAABSTRACT Carbapenem-resistant (CR) sequence type 258 (ST258) Klebsiella pneumoniae has become an urgent health care threat, causing an increasing number of high-mortality infections. Its resistance to numerous antibiotics and threat to immunocompromised patients necessitate finding new therapies to combat these infections. Previous successes in the laboratory, as well as the conservation of capsular polysaccharide (CPS) among the members of the ST258 clone, suggest that monoclonal antibody (MAb) therapy targeting the outer polysaccharide capsule of K. pneumoniae could serve as a valuable treatment alternative for afflicted patients. Here, we isolated several IgG antibodies from mice inoculated with a mixture of CR K. pneumoniae CPS conjugated to anthrax protective antigen. Two of these MAbs, 17H12 and 8F12, bind whole and oligosaccharide epitopes of the CPS of clade 2 ST258 CR K. pneumoniae, which is responsible for the most virulent CR K. pneumoniae infections in the United States. These antibodies were shown to agglutinate all clade 2 strains and were also shown to promote extracellular processes killing these bacteria, including biofilm inhibition, complement deposition, and deployment of neutrophil extracellular traps. Additionally, they promoted opsonophagocytosis and intracellular killing of CR K. pneumoniae by human-derived neutrophils and cultured murine macrophages. Finally, when mice were intratracheally infected with preopsonized clade 2 CR K. pneumoniae, these MAbs reduced bacterial dissemination to organs. Our data suggest that broadly reactive anticapsular antibodies and vaccines against clade 2 ST258 CR K. pneumoniae are possible. Such MAbs and vaccines would benefit those susceptible populations at risk of infection with this group of multidrug-resistant bacteria. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is an enteric bacterium that has been responsible for an increasing number of deadly outbreaks and hospital-acquired infections. The pathogen’s resistance to numerous antibiotics, including new drugs, leaves few therapeutic options available for infected patients, who often are too sick to fight the infection themselves. Immunotherapy utilizing monoclonal antibodies has been successful in other medical fields, and antibodies targeting the outer polysaccharide capsule of these bacteria could be a valuable treatment alternative. This study presents two anticapsular antibodies, 17H12 and 8F12, that were found to be protective against the most virulent carbapenem-resistant K. pneumoniae clinical strains. These antibodies are shown to promote the killing of these strains through several extracellular and intracellular processes and prevent the spread of infection in mice from the lungs to distal organs. Thus, they could ultimately treat or protect patients infected or at risk of infection by this multidrug-resistant bacterium.https://journals.asm.org/doi/10.1128/mBio.00091-18adjuvant therapyantibiotic resistancecarbapenem resistanceinfection protectionKlebsiella pneumoniaemonoclonal antibodies |
| spellingShingle | Elizabeth Diago-Navarro Michael P. Motley Gonzalo Ruiz-Peréz Winnie Yu Julianne Austin Bruna M. S. Seco Guozhi Xiao Aniska Chikhalya Peter H. Seeberger Bettina C. Fries Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Protect from Infection mBio adjuvant therapy antibiotic resistance carbapenem resistance infection protection Klebsiella pneumoniae monoclonal antibodies |
| title | Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Protect from Infection |
| title_full | Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Protect from Infection |
| title_fullStr | Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Protect from Infection |
| title_full_unstemmed | Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Protect from Infection |
| title_short | Novel, Broadly Reactive Anticapsular Antibodies against Carbapenem-Resistant <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> Protect from Infection |
| title_sort | novel broadly reactive anticapsular antibodies against carbapenem resistant named content content type genus species klebsiella pneumoniae named content protect from infection |
| topic | adjuvant therapy antibiotic resistance carbapenem resistance infection protection Klebsiella pneumoniae monoclonal antibodies |
| url | https://journals.asm.org/doi/10.1128/mBio.00091-18 |
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