Publicação
Pneumococcal adaptation: from colonization to disease
| Resumo: | Streptococcus pneumoniae (pneumococcus) is a Gram-positive colonizer of the human nasopharynx. It is also responsible for several diseases such as pneumonia, bacteremia and meningitis. The transition from asymptomatic colonization to disease is accompanied by drastic changes in the host physiological conditions such as temperature, nutrient availability and pH, and in the mode of growth of the pathogen – from biofilm to planktonic (in case of invasive disease). The pneumococcal within-host adaptation mechanisms during the transition from carriage to disease are still poorly understood. In this study, we investigated the differences in the phenotype of invasive (isolated from normally sterile body sites) and carriage (isolated from the nasopharynx) pairs of strains obtained from single patients with invasive pneumococcal disease (IPD). We characterized strains obtained from 10 patients: 8 capsular type (serotype) matching pairs, and 2 non-serotype matching pairs. In particular, the strains were tested for biofilm formation capacity (to mimic growth in the nasopharynx) and planktonic growth ability (to mimic liquid body sites) and biofilm cell dispersal by heat exposure (to mimic fever). Finally dual-strain competition assays in biofilm and planktonic growth were performed for one pair. Whilst having essentially the same genetic background significant differences were observed on the phenotypic assays carried out under the framework of this thesis. We observed that the biofilm cell viability of invasive strains was significantly higher or equal to the biofilm cell viability of the respective carriage serotype-matching strain. We observed that all invasive strains had biofilm dispersal rates higher than the respective carriage serotype-matching strain, except for one pair in which differences were not observed. Planktonic growth rates and maximum optical densities (OD) were obtained from growth curves but no pattern was observed across all pairs of strains. Finally, four strains obtained from co-colonization from a single patient were tested in dual-strain competition assays during planktonic and biofilm growth. Interestingly, we observed an ecological interaction during biofilm growth, in which one of the carriage strains was not affected by any of the other strains, but negatively affected the growth of all the other strains. Concluding, we demonstrate that regardless of having a similar genetic background, significant phenotypic differences can be observed between invasive and carriage pairs of strains. Invasive strains tend to have higher biofilm cell viability and biofilm dispersal rates than carriage strains, which makes these strains fitter to invasion. We hypothesize that the transcriptomic profile of these strains might explain the phenotypic differences observed in this study. |
|---|---|
| Autores principais: | Queirós, Miguel Ângelo Teixeira |
| Assunto: | Streptococcus pneumoniae Doença invasiva pneumocócica Adaptação no hospedeiro Crescimento planctónico e em biofilme Competição Teses de mestrado - 2019 |
| Ano: | 2019 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Streptococcus pneumoniae (pneumococcus) is a Gram-positive colonizer of the human nasopharynx. It is also responsible for several diseases such as pneumonia, bacteremia and meningitis. The transition from asymptomatic colonization to disease is accompanied by drastic changes in the host physiological conditions such as temperature, nutrient availability and pH, and in the mode of growth of the pathogen – from biofilm to planktonic (in case of invasive disease). The pneumococcal within-host adaptation mechanisms during the transition from carriage to disease are still poorly understood. In this study, we investigated the differences in the phenotype of invasive (isolated from normally sterile body sites) and carriage (isolated from the nasopharynx) pairs of strains obtained from single patients with invasive pneumococcal disease (IPD). We characterized strains obtained from 10 patients: 8 capsular type (serotype) matching pairs, and 2 non-serotype matching pairs. In particular, the strains were tested for biofilm formation capacity (to mimic growth in the nasopharynx) and planktonic growth ability (to mimic liquid body sites) and biofilm cell dispersal by heat exposure (to mimic fever). Finally dual-strain competition assays in biofilm and planktonic growth were performed for one pair. Whilst having essentially the same genetic background significant differences were observed on the phenotypic assays carried out under the framework of this thesis. We observed that the biofilm cell viability of invasive strains was significantly higher or equal to the biofilm cell viability of the respective carriage serotype-matching strain. We observed that all invasive strains had biofilm dispersal rates higher than the respective carriage serotype-matching strain, except for one pair in which differences were not observed. Planktonic growth rates and maximum optical densities (OD) were obtained from growth curves but no pattern was observed across all pairs of strains. Finally, four strains obtained from co-colonization from a single patient were tested in dual-strain competition assays during planktonic and biofilm growth. Interestingly, we observed an ecological interaction during biofilm growth, in which one of the carriage strains was not affected by any of the other strains, but negatively affected the growth of all the other strains. Concluding, we demonstrate that regardless of having a similar genetic background, significant phenotypic differences can be observed between invasive and carriage pairs of strains. Invasive strains tend to have higher biofilm cell viability and biofilm dispersal rates than carriage strains, which makes these strains fitter to invasion. We hypothesize that the transcriptomic profile of these strains might explain the phenotypic differences observed in this study. |
|---|