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Use of commensal streptococci to prevent pneumococcal colonization / Bárbara Miranda Ferreira ; orient. Raquel Sá-Leão

Main Author Ferreira, Bárbara Miranda Secondary Author Sá-Leão, Raquel Language Inglês. Country Portugal. Publication Lisboa : NOVA Medical School, 2019 Description vii, 56 p. : il. Abstract Streptococcus pneumoniae (pneumococcus) colonizes the upper respiratory tract, and is a leading cause of otitis media, pneumonia, bacteremia and meningitis. Vaccines and antibiotics are used to fight this pathobiont. The pneumococcal conjugate vaccines are restricted in valency, being efficient against certain serotypes; antibiotics, have broad-spectrum activities, affecting the microbiota and selecting for resistance. Consequently, novel strategies are needed to complement the existing ones. S. pneumoniae frequently co-colonize the respiratory tract together with other streptococci. Colonization dynamics is affected by several factors such as interspecies competition. The goal of this thesis was the characterization of seven commensal streptococcal strains, strains A-G, with high inhibitory activity against Streptococcus pneumoniae. Whole-genome sequencing of the seven candidate strains enabled species identification and in silico search of bacteriocin-related loci. Strain A was classified as S. oralis and strains B-G as S. mitis. Three types of bacteriocin-related loci were found: blp, streptococcin and lantibiotic. These loci were further characterized in genetic content, organization and diversity. In order to determine if excreted products of the seven candidate strains had inhibitory activity, the strains supernatants were tested against a control pneumococcal strain. All supernatants of the S. mitis strains inhibited the strain. Finally, we deleted the bacteriocin and immunity region of the B1.1. blp locus of strain F. The mutant strain inhibitory profile was evaluated against a previously tested pneumococcal collection. In all assays, there was a loss or attenuation of the inhibitory profile. Our results demonstrate that a blp locus from a commensal streptococcal strain encodes for bacteriocins active against Streptococcus pneumoniae. Topical name Streptococcus
Commensal
Interspecies interactions
Bacteriocins
Academic Dissertation
Portugal
Index terms Dissertação de Mestrado
Microbiologia Médica
Universidade NOVA de Lisboa
NOVA Medical School
2019
CDU 616 Online Resources Click here to access the eletronic resource http://hdl.handle.net/10362/92372
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Documento Eletrónico Biblioteca NMS|FCM
online
RUN http://hdl.handle.net/10362/92372 Available 20210024

Streptococcus pneumoniae (pneumococcus) colonizes the upper respiratory tract, and is a leading cause of otitis media, pneumonia, bacteremia and meningitis. Vaccines and antibiotics are used to fight this pathobiont. The pneumococcal conjugate vaccines are restricted in valency, being efficient against certain serotypes; antibiotics, have broad-spectrum activities, affecting the microbiota and selecting for resistance. Consequently, novel strategies are needed to complement the existing ones. S. pneumoniae frequently co-colonize the respiratory tract together with other streptococci. Colonization dynamics is affected by several factors such as interspecies competition. The goal of this thesis was the characterization of seven commensal streptococcal strains, strains A-G, with high inhibitory activity against Streptococcus pneumoniae. Whole-genome sequencing of the seven candidate strains enabled species identification and in silico search of bacteriocin-related loci. Strain A was classified as S. oralis and strains B-G as S. mitis. Three types of bacteriocin-related loci were found: blp, streptococcin and lantibiotic. These loci were further characterized in genetic content, organization and diversity. In order to determine if excreted products of the seven candidate strains had inhibitory activity, the strains supernatants were tested against a control pneumococcal strain. All supernatants of the S. mitis strains inhibited the strain. Finally, we deleted the bacteriocin and immunity region of the B1.1. blp locus of strain F. The mutant strain inhibitory profile was evaluated against a previously tested pneumococcal collection. In all assays, there was a loss or attenuation of the inhibitory profile. Our results demonstrate that a blp locus from a commensal streptococcal strain encodes for bacteriocins active against Streptococcus pneumoniae.

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