Modelling invasive group A streptococcal disease using bioluminescence

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 a...

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Bibliographic Details
Published in:	BMC microbiology Vol. 18; no. 1; p. 60
Main Authors:	Lamb, L E, Zhi, X, Alam, F, Pyzio, M, Scudamore, C L, Wiles, S, Sriskandan, S
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 19-06-2018 BioMed Central BMC
Subjects:	Analysis Animals Antibiotics Antigens, Bacterial - genetics Bacteria Bacterial Outer Membrane Proteins - genetics Bioluminescence Biophotonic imaging Carrier Proteins - genetics Disease Disease Models, Animal Disease transmission Drug development Drug therapy Experiments Female Fitness Galleria mellonella Genetic Fitness Group A Streptococcus Health sciences Humans Infection model Infections Inflammatory diseases Invasive disease Light Luciferase Luminescent Measurements Luminescent Proteins - genetics Luminescent Proteins - metabolism Medical research Methodology Mice Modelling Operon Pathogenesis Photonics Replication Respiratory Tract Infections - microbiology Stability Strains (organisms) Streptococcal infections Streptococcal Infections - microbiology Streptococcus Streptococcus infections Streptococcus pyogenes Streptococcus pyogenes - genetics Streptococcus pyogenes - pathogenicity Vaccines United Kingdom > UK Bioluminescence Biophotonic imaging Luciferase Group A Streptococcus Streptococcus pyogenes Invasive disease Infection model
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Summary:	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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2180 1471-2180
DOI:	10.1186/s12866-018-1200-1