Identification of Genes That Contribute to the Pathogenesis of Invasive Pneumococcal Disease by
            <i>In Vivo</i>
            Transcriptomic Analysis

Ogunniyi, Abiodun D.; Mahdi, Layla K.; Trappetti, Claudia; Verhoeven, Nadine; Mermans, Daphne; Hoek, Mark B. Van der; Plumptre, Charles D.; Paton, James C.

doi:10.1128/iai.00295-12

Cited by 66 publications

(73 citation statements)

References 51 publications

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“…pneumoniae is a diverse and adaptable pathogen, capable of surviving in a range of niches within its human host. Previous studies from our laboratory have identified changes in in vivo transcriptional profile within a given strain that facilitate survival in distinct host niches (nasopharynx, lungs, blood, and brain) and/or aid progression from one niche to another (26,27,35,36). However, genetic differences between strains also result in pneumococci with inherent tropism for one niche over another.…”

Section: Discussionmentioning

confidence: 79%

Site of Isolation Determines Biofilm Formation and Virulence Phenotypes of Streptococcus pneumoniae Serotype 3 Clinical Isolates

et al. 2013

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Streptococcus pneumoniae is a diverse species causing invasive as well as localized infections that result in massive global morbidity and mortality. Strains vary markedly in pathogenic potential, but the molecular basis is obscured by the diversity and plasticity of the pneumococcal genome. In the present study, S. pneumoniae serotype 3 blood (n ‫؍‬ 12) or ear (n ‫؍‬ 13) isolates were multilocus sequence typed (MLST) and assessed for biofilm formation and virulence phenotype. Blood and ear isolates exhibited similar MLST distributions but differed markedly in phenotype. Blood isolates formed robust biofilms only at pH 7.4, which were enhanced in Fe(III)-supplemented medium. Conversely, ear isolates formed biofilms only at pH 6.8, and Fe(III) was inhibitory. Biofilm formation paralleled luxS expression and genetic competence. In a mouse intranasal challenge model, blood isolates did not stably colonize the nasopharynx but spread to the blood; none spread to the ear. Ear isolates colonized the nasopharynx at higher levels and also spread to the ear compartment in a significant proportion of animals; none caused bacteremia. Thus, pneumococci of the same serotype and MLST exhibit distinct phenotypes in accordance with clinical site of isolation, indicative of stable niche adaptation within a clonal lineage.

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Section: Discussionmentioning

confidence: 79%

Site of Isolation Determines Biofilm Formation and Virulence Phenotypes of Streptococcus pneumoniae Serotype 3 Clinical Isolates

et al. 2013

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“…S. pneumoniae contains genes encoding at least 20 carbohydrate transporters in the core genome (66) and can ferment Ͼ30 different carbohydrates (67). Genes regulating carbohydrate metabolism, PTS, and ABC transporters have been identified as important during tissue-specific disease (29,68,69). Carbohydrate metabolism may provide selective advantages in different host niches, as the carbon source availability in the nasopharynx will be drastically different from other body sites.…”

Section: Discussionmentioning

confidence: 99%

“…pneumoniae transcriptional profiles change in response to environmental stimuli and differ between the upper respiratory tract and other tissue sites (28,29). Understanding how transcriptional profiles are altered under various conditions will provide a critical step to understanding mechanisms that underlie progression from biofilm colonization to disease.…”

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confidence: 99%

Dynamic Changes in the Streptococcus pneumoniae Transcriptome during Transition from Biofilm Formation to Invasive Disease upon Influenza A Virus Infection

et al. 2014

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f Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis.

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“…Mutant and wild-type bacteria were grown separately in serum broth and then mixed at an input ratio of 1:1, and 50 l of bacterial suspension was used to challenge mice intranasally under anesthesia. Nasal wash, nasal tissue, lung, and blood samples were collected and processed as described previously (26,27). Each sample was serially diluted and plated on blood agar and on blood agar with erythromycin to determine the ratio of mutant to wild-type bacteria.…”

Section: Construction Of Mutantsmentioning

confidence: 99%

Surface Association of Pht Proteins of Streptococcus pneumoniae

2013

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Streptococcus pneumoniae is a major human pathogen responsible for massive global morbidity and mortality. The pneumococcus attaches a variety of proteins to its cell surface, many of which contribute to virulence; one such family are the polyhistidine triad (Pht) proteins PhtA, PhtB, PhtD, and PhtE. In this study, we have examined the mechanism of Pht surface attachment using PhtD as a model. Analysis of deletion and point mutants identified a three-amino-acid region of PhtD (Q27-H28-R29) that is critical for the process. The analogous region in PhtE was also necessary for its attachment to the cell surface. Furthermore, we show that a large proportion of the total amount of each Pht protein is released into bacterial culture supernatants. Other surface proteins were also released, albeit to lesser extents, and this was not due to pneumococcal autolysis. The extent of release of surface proteins was strain dependent and was not affected by the capsule. Lastly, we compared the fitness of wild-type and ⌬phtABDE pneumococci in vivo in a mouse coinfection model. Release of Pht proteins by the wild type did not complement the mutant strain, consistent with surface-attached rather than soluble forms of the Pht proteins playing the major role in virulence. The significant degree of release of Pht proteins from intact bacteria may have implications for the use of these proteins in novel vaccines.

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Identification of Genes That Contribute to the Pathogenesis of Invasive Pneumococcal Disease by In Vivo Transcriptomic Analysis

Cited by 66 publications

References 51 publications

Site of Isolation Determines Biofilm Formation and Virulence Phenotypes of Streptococcus pneumoniae Serotype 3 Clinical Isolates

Site of Isolation Determines Biofilm Formation and Virulence Phenotypes of Streptococcus pneumoniae Serotype 3 Clinical Isolates

Dynamic Changes in the Streptococcus pneumoniae Transcriptome during Transition from Biofilm Formation to Invasive Disease upon Influenza A Virus Infection

Surface Association of Pht Proteins of Streptococcus pneumoniae

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