Terra, VS;
Plumptre, CD;
Wall, EC;
Brown, JS;
Wren, BW;
(2020)
Construction of a pneumolysin deficient mutant in streptococcus pneumoniae serotype 1 strain 519/43 and phenotypic characterisation.
Microbial Pathogenesis
, 141
, Article 103999. 10.1016/j.micpath.2020.103999.
(In press).
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Abstract
Streptococcus pneumoniae capsular serotype 1 continues to pose a huge infectious disease burden in low- and middle-income countries, particularly in West Africa. However, studies on this important serotype have been hampered by the inability to genetically modify these strains. In this study we have genetically modified a serotype 1 strain (519/43), the first time that this has been achieved for this serotype, providing the methodology for a deeper understanding of its biology and pathogenicity. As proof of principle we constructed a defined pneumolysin mutant and showed that it lost its ability to lyse red blood cells. We also showed that when mice were infected intranasally with the mutant 519/43Δply there was no significant difference between the load of bacteria in lungs and blood when compared to the wild type 519/43. When mice were infected intraperitoneally there were significantly fewer bacteria recovered from blood for the mutant 519/43Δply strain, although all mice still displayed signs of disease. Our study demonstrates S. pneumoniae serotype 1 strains can be genetically manipulated using our methodology and demonstrate that the ability to cause pneumonia in mice is independent of active pneumolysin for the 519/43 serotype 1 strain.
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