Modelling invasive group A streptococcal disease using bioluminescence
Abstract Background The development of vaccines and evaluation of novel treatment strategies for invasive group A streptococcal (iGAS) disease requires suitable models of human infection that can be monitored longitudinally and are preferably non-invasive. Bio-photonic imaging provides an opportunit...
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| Format: | Article |
| Language: | English |
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BMC
2018-06-01
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| Series: | BMC Microbiology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12866-018-1200-1 |
| _version_ | 1819231876798218240 |
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| author | L. E. Lamb X. Zhi F. Alam M. Pyzio C. L. Scudamore S. Wiles S. Sriskandan |
| author_facet | L. E. Lamb X. Zhi F. Alam M. Pyzio C. L. Scudamore S. Wiles S. Sriskandan |
| author_sort | L. E. Lamb |
| collection | DOAJ |
| description | Abstract Background The development of vaccines and evaluation of novel treatment strategies for invasive group A streptococcal (iGAS) disease requires suitable models of human infection that can be monitored longitudinally and are preferably non-invasive. Bio-photonic imaging provides an opportunity to reduce use of animals in infection modelling and refine the information that can be obtained, however the range of bioluminescent GAS strains available is limited. In this study we set out to develop bioluminescent iGAS strains for use in in vivo pneumonia and soft tissue disease models. Results Using clinical emm1, emm3, and emm89 GAS strains that were transformed with constructs carrying the luxABCDE operon, growth and bioluminescence of transformed strains were characterised in vitro and in vivo. Emm3 and emm89 strains expressed detectable bioluminescence when transformed with a replicating plasmid and light production correlated with viable bacterial counts in vitro, however plasmid instability precluded use in the absence of antimicrobial pressure. Emm89 GAS transformed with an integrating construct demonstrated stable bioluminescence that was maintained in the absence of antibiotics. Bioluminescence of the emm89 strain correlated with viable bacterial counts both in vitro and immediately following infection in vivo. Although bioluminescence conferred a detectable fitness burden to the emm89 strain during soft tissue infection in vivo, it did not prevent dissemination to distant tissues. Conclusion Development of stably bioluminescent GAS for use in vitro and in vivo models of infection should facilitate development of novel therapeutics and vaccines while also increasing our understanding of infection progression and transmission routes. |
| first_indexed | 2024-12-23T11:51:56Z |
| format | Article |
| id | doaj.art-ea43b8960075495cb699cb7e456eddd3 |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-12-23T11:51:56Z |
| publishDate | 2018-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj.art-ea43b8960075495cb699cb7e456eddd32022-12-21T17:48:11ZengBMCBMC Microbiology1471-21802018-06-0118111010.1186/s12866-018-1200-1Modelling invasive group A streptococcal disease using bioluminescenceL. E. Lamb0X. Zhi1F. Alam2M. Pyzio3C. L. Scudamore4S. Wiles5S. Sriskandan6Section of Infectious Diseases and Immunity, Department of Medicine, Imperial College LondonSection of Infectious Diseases and Immunity, Department of Medicine, Imperial College LondonSection of Infectious Diseases and Immunity, Department of Medicine, Imperial College LondonSection of Infectious Diseases and Immunity, Department of Medicine, Imperial College LondonMRC Harwell, Harwell Science and Innovation CampusSection of Infectious Diseases and Immunity, Department of Medicine, Imperial College LondonSection of Infectious Diseases and Immunity, Department of Medicine, Imperial College LondonAbstract Background The development of vaccines and evaluation of novel treatment strategies for invasive group A streptococcal (iGAS) disease requires suitable models of human infection that can be monitored longitudinally and are preferably non-invasive. Bio-photonic imaging provides an opportunity to reduce use of animals in infection modelling and refine the information that can be obtained, however the range of bioluminescent GAS strains available is limited. In this study we set out to develop bioluminescent iGAS strains for use in in vivo pneumonia and soft tissue disease models. Results Using clinical emm1, emm3, and emm89 GAS strains that were transformed with constructs carrying the luxABCDE operon, growth and bioluminescence of transformed strains were characterised in vitro and in vivo. Emm3 and emm89 strains expressed detectable bioluminescence when transformed with a replicating plasmid and light production correlated with viable bacterial counts in vitro, however plasmid instability precluded use in the absence of antimicrobial pressure. Emm89 GAS transformed with an integrating construct demonstrated stable bioluminescence that was maintained in the absence of antibiotics. Bioluminescence of the emm89 strain correlated with viable bacterial counts both in vitro and immediately following infection in vivo. Although bioluminescence conferred a detectable fitness burden to the emm89 strain during soft tissue infection in vivo, it did not prevent dissemination to distant tissues. Conclusion Development of stably bioluminescent GAS for use in vitro and in vivo models of infection should facilitate development of novel therapeutics and vaccines while also increasing our understanding of infection progression and transmission routes.http://link.springer.com/article/10.1186/s12866-018-1200-1BioluminescenceBiophotonic imagingGroup A StreptococcusInfection modelInvasive diseaseLuciferase |
| spellingShingle | L. E. Lamb X. Zhi F. Alam M. Pyzio C. L. Scudamore S. Wiles S. Sriskandan Modelling invasive group A streptococcal disease using bioluminescence BMC Microbiology Bioluminescence Biophotonic imaging Group A Streptococcus Infection model Invasive disease Luciferase |
| title | Modelling invasive group A streptococcal disease using bioluminescence |
| title_full | Modelling invasive group A streptococcal disease using bioluminescence |
| title_fullStr | Modelling invasive group A streptococcal disease using bioluminescence |
| title_full_unstemmed | Modelling invasive group A streptococcal disease using bioluminescence |
| title_short | Modelling invasive group A streptococcal disease using bioluminescence |
| title_sort | modelling invasive group a streptococcal disease using bioluminescence |
| topic | Bioluminescence Biophotonic imaging Group A Streptococcus Infection model Invasive disease Luciferase |
| url | http://link.springer.com/article/10.1186/s12866-018-1200-1 |
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