Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Clinical Isolates: In Vivo Virulence Assessment in <i>Galleria mellonella</i> and Potential Therapeutics by Polycationic Oligoethyleneimine
<i>Klebsiella pneumoniae</i>, one of the most common pathogens found in hospital-acquired infections, is often resistant to multiple antibiotics. In fact, multidrug-resistant (MDR) <i>K. pneumoniae</i> producing KPC or OXA-48-like carbapenemases are recognized as a serious gl...
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MDPI AG
2021-01-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/1/56 |
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| author | Dalila Mil-Homens Maria Martins José Barbosa Gabriel Serafim Maria J. Sarmento Rita F. Pires Vitória Rodrigues Vasco D.B. Bonifácio Sandra N. Pinto |
| author_facet | Dalila Mil-Homens Maria Martins José Barbosa Gabriel Serafim Maria J. Sarmento Rita F. Pires Vitória Rodrigues Vasco D.B. Bonifácio Sandra N. Pinto |
| author_sort | Dalila Mil-Homens |
| collection | DOAJ |
| description | <i>Klebsiella pneumoniae</i>, one of the most common pathogens found in hospital-acquired infections, is often resistant to multiple antibiotics. In fact, multidrug-resistant (MDR) <i>K. pneumoniae</i> producing KPC or OXA-48-like carbapenemases are recognized as a serious global health threat. In this sense, we evaluated the virulence of <i>K. pneumoniae</i> KPC(+) or OXA-48(+) aiming at potential antimicrobial therapeutics. <i>K. pneumoniae</i> carbapenemase (KPC) and the expanded-spectrum oxacillinase OXA-48 isolates were obtained from patients treated in medical care units in Lisbon, Portugal. The virulence potential of the <i>K. pneumonia</i> clinical isolates was tested using the <i>Galleria mellonella</i> model. For that, <i>G. mellonella</i> larvae were inoculated using patients KPC(+) and OXA-48(+) isolates. Using this in vivo model, the KPC(+) <i>K. pneumoniae</i> isolates showed to be, on average, more virulent than OXA-48(+). Virulence was found attenuated when a low bacterial inoculum (one magnitude lower) was tested. In addition, we also report the use of a synthetic polycationic oligomer (L-OEI-h) as a potential antimicrobial agent to fight infectious diseases caused by MDR bacteria. L-OEI-h has a broad-spectrum antibacterial activity and exerts a significantly bactericidal activity within the first 5-30 min treatment, causing lysis of the cytoplasmic membrane. Importantly, the polycationic oligomer showed low toxicity against in vitro models and no visible cytotoxicity (measured by survival and health index) was noted on the in vivo model <i>(G. mellonella)</i>, thus L-OEI-h is foreseen as a promising polymer therapeutic for the treatment of MDR <i>K. pneumoniae</i> infections. |
| first_indexed | 2024-03-09T05:35:28Z |
| format | Article |
| id | doaj.art-52b4ade8e63a4198917180695744fbe6 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T05:35:28Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-52b4ade8e63a4198917180695744fbe62023-12-03T12:29:28ZengMDPI AGAntibiotics2079-63822021-01-011015610.3390/antibiotics10010056Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Clinical Isolates: In Vivo Virulence Assessment in <i>Galleria mellonella</i> and Potential Therapeutics by Polycationic OligoethyleneimineDalila Mil-Homens0Maria Martins1José Barbosa2Gabriel Serafim3Maria J. Sarmento4Rita F. Pires5Vitória Rodrigues6Vasco D.B. Bonifácio7Sandra N. Pinto8iBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, PortugalJ. Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejskova 3, 18223 Prague, Czech RepubliciBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, PortugalSecção de Microbiologia, Laboratório SYNLAB-Lisboa, Grupo SYNLAB Portugal, Av. Columbano Bordalo Pinheiro, 75 A, 2° Andar, 1070-061 Lisboa, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, PortugaliBB—Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal<i>Klebsiella pneumoniae</i>, one of the most common pathogens found in hospital-acquired infections, is often resistant to multiple antibiotics. In fact, multidrug-resistant (MDR) <i>K. pneumoniae</i> producing KPC or OXA-48-like carbapenemases are recognized as a serious global health threat. In this sense, we evaluated the virulence of <i>K. pneumoniae</i> KPC(+) or OXA-48(+) aiming at potential antimicrobial therapeutics. <i>K. pneumoniae</i> carbapenemase (KPC) and the expanded-spectrum oxacillinase OXA-48 isolates were obtained from patients treated in medical care units in Lisbon, Portugal. The virulence potential of the <i>K. pneumonia</i> clinical isolates was tested using the <i>Galleria mellonella</i> model. For that, <i>G. mellonella</i> larvae were inoculated using patients KPC(+) and OXA-48(+) isolates. Using this in vivo model, the KPC(+) <i>K. pneumoniae</i> isolates showed to be, on average, more virulent than OXA-48(+). Virulence was found attenuated when a low bacterial inoculum (one magnitude lower) was tested. In addition, we also report the use of a synthetic polycationic oligomer (L-OEI-h) as a potential antimicrobial agent to fight infectious diseases caused by MDR bacteria. L-OEI-h has a broad-spectrum antibacterial activity and exerts a significantly bactericidal activity within the first 5-30 min treatment, causing lysis of the cytoplasmic membrane. Importantly, the polycationic oligomer showed low toxicity against in vitro models and no visible cytotoxicity (measured by survival and health index) was noted on the in vivo model <i>(G. mellonella)</i>, thus L-OEI-h is foreseen as a promising polymer therapeutic for the treatment of MDR <i>K. pneumoniae</i> infections.https://www.mdpi.com/2079-6382/10/1/56<i>Klebsiella pneumoniae</i>KPC and OXA-48-like carbapenemases<i>Galleria mellonella</i> infection modellinear oligoethyleneimine hydrochloride |
| spellingShingle | Dalila Mil-Homens Maria Martins José Barbosa Gabriel Serafim Maria J. Sarmento Rita F. Pires Vitória Rodrigues Vasco D.B. Bonifácio Sandra N. Pinto Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Clinical Isolates: In Vivo Virulence Assessment in <i>Galleria mellonella</i> and Potential Therapeutics by Polycationic Oligoethyleneimine Antibiotics <i>Klebsiella pneumoniae</i> KPC and OXA-48-like carbapenemases <i>Galleria mellonella</i> infection model linear oligoethyleneimine hydrochloride |
| title | Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Clinical Isolates: In Vivo Virulence Assessment in <i>Galleria mellonella</i> and Potential Therapeutics by Polycationic Oligoethyleneimine |
| title_full | Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Clinical Isolates: In Vivo Virulence Assessment in <i>Galleria mellonella</i> and Potential Therapeutics by Polycationic Oligoethyleneimine |
| title_fullStr | Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Clinical Isolates: In Vivo Virulence Assessment in <i>Galleria mellonella</i> and Potential Therapeutics by Polycationic Oligoethyleneimine |
| title_full_unstemmed | Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Clinical Isolates: In Vivo Virulence Assessment in <i>Galleria mellonella</i> and Potential Therapeutics by Polycationic Oligoethyleneimine |
| title_short | Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Clinical Isolates: In Vivo Virulence Assessment in <i>Galleria mellonella</i> and Potential Therapeutics by Polycationic Oligoethyleneimine |
| title_sort | carbapenem resistant i klebsiella pneumoniae i clinical isolates in vivo virulence assessment in i galleria mellonella i and potential therapeutics by polycationic oligoethyleneimine |
| topic | <i>Klebsiella pneumoniae</i> KPC and OXA-48-like carbapenemases <i>Galleria mellonella</i> infection model linear oligoethyleneimine hydrochloride |
| url | https://www.mdpi.com/2079-6382/10/1/56 |
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