Genomics, Genetic Variation, and Regions of Differences

Tettelin, Hervé; Chancey, Scott; Mitchell, Tim; Denapaite, Dalia; Schähle, Yvonne; Rieger, Martin; Hakenbeck, Regine

doi:10.1016/b978-0-12-410530-0.00005-3

Cited by 8 publications

(20 citation statements)

References 136 publications

(111 reference statements)

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“…Determination to the species level is aggravated by the capacity for genetic transformation in viridans streptococci. The large accessory genome bears many signs of interspecies gene transfer, including large genomic islands common among different streptococcal species, leading to a smooth transition between species in comparative genomic hybridization experiments of oral streptococci ( 3 , 4 , 88 ). In this context, it is remarkable that csRNA genes apparently serve as entry sites for horizontal gene transfer in several cases, as described here, thereby contributing to the genomic variability observed for S. oralis and resulting in an overlap in the accessory genomes of S. oralis and S. infantis .…”

Section: Discussionmentioning

confidence: 99%

“…Strains carrying mutations in these genes are less virulent in mouse models. However, most of them are probably required for host interaction rather than being directly responsible for disease since in most cases homologs are present in S. pneumoniae ’s nonpathogenic commensal relatives S. mitis and S. pseudopneumoniae ( 2 – 4 ). There are only a few components that are clearly associated with S. pneumoniae and which are not or are only rarely found in commensal streptococci: the pneumolysin Ply, a pore-forming toxin whose gene is located on an islet together with the autolysin gene lytA , and the three choline-binding proteins (CBPs) PspA, PcpA, and PspC, including the Hic variant of Psp and the hyaluronidase HlyA.…”

Section: Introductionmentioning

confidence: 99%

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Highly Variable Streptococcus oralis Strains Are Common among Viridans Streptococci Isolated from Primates

Denapaite

Rieger

Köndgen

et al. 2016

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Streptococcus pneumoniae is a rare example of a human-pathogenic bacterium among viridans streptococci, which consist of commensal symbionts, such as the close relatives Streptococcus mitis and S. oralis. We have shown that S. oralis can frequently be isolated from primates and a variety of other viridans streptococci as well. Genes and genomic islands which are known pneumococcal virulence factors are present in S. oralis and S. mitis, documenting the widespread occurrence of these compounds, which encode surface and secreted proteins. The frequent occurrence of CRISP-Cas gene clusters and a surprising variation of a set of small noncoding RNAs are factors to be considered in future research to further our understanding of mechanisms involved in the genomic diversity driven by horizontal gene transfer among viridans streptococci.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Highly Variable Streptococcus oralis Strains Are Common among Viridans Streptococci Isolated from Primates

Denapaite

Rieger

Köndgen

et al. 2016

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“…Streptococcus pneumoniae’s virulence thrives because of the bacteria’s ability to acquire new genetic material via transformation and recombination ( 117 ). Investigating the level of genetic variation within S. pneumoniae is important for not only thoroughly understanding its virulence but also for developing effective treatments and vaccines.…”

Section: Virulence Factorsmentioning

confidence: 99%

“…Investigating the level of genetic variation within S. pneumoniae is important for not only thoroughly understanding its virulence but also for developing effective treatments and vaccines. About 4,000 S. pneumoniae genomes have already been sequenced ( 117 ), with lengths ~2–2.2 million bp ( 54 ). More than 2,000 genes have been annotated, but novel genes are still regularly discovered as more sequences become available ( 117 ).…”

Section: Virulence Factorsmentioning

confidence: 99%

Streptococcus pneumoniae’s Virulence and Host Immunity: Aging, Diagnostics, and Prevention

2018

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Streptococcus pneumoniae is an infectious pathogen responsible for millions of deaths worldwide. Diseases caused by this bacterium are classified as pneumococcal diseases. This pathogen colonizes the nasopharynx of its host asymptomatically, but overtime can migrate to sterile tissues and organs and cause infections. Pneumonia is currently the most common pneumococcal disease. Pneumococcal pneumonia is a global health concern and vastly affects children under the age of five as well as the elderly and individuals with pre-existing health conditions. S. pneumoniae has a large selection of virulence factors that promote adherence, invasion of host tissues, and allows it to escape host immune defenses. A clear understanding of S. pneumoniae’s virulence factors, host immune responses, and examining the current techniques available for diagnosis, treatment, and disease prevention will allow for better regulation of the pathogen and its diseases. In terms of disease prevention, other considerations must include the effects of age on responses to vaccines and vaccine efficacy. Ongoing work aims to improve on current vaccination paradigms by including the use of serotype-independent vaccines, such as protein and whole cell vaccines. Extending our knowledge of the biology of, and associated host immune response to S. pneumoniae is paramount for our improvement of pneumococcal disease diagnosis, treatment, and improvement of patient outlook.

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“…Fonte: A -Arquivo pessoal; B -VAN DER POLL et al 2009A B sequenciamento de um grande número de isolados mostraram que o pneumococo possui uma grande variabilidade gênica. As regiões com maior nível de recombinação são os loci contendo genes de resistência a antibióticos e genes envolvidos na síntese de PS, tornando esta bactéria altamente adaptável (CROUCHER et al, 2011;HSIEH et al, 2013;TETTELIN et al, 2015). A troca gênica entre espécies relacionadas fornece ainda um importante mecanismo de evolução do pneumococo (DONATI et al, 2010).…”

Section: Figura 1 -Características Do Pneumococounclassified

Imunização pulmonar com nanopartículas contendo o antígeno PspA (Pneumococcal surface protein A)

Rodrigues¹

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Streptococcus pneumoniae, or pneumococcus, is part of the human microbiota, but in some cases it can cause diseases, such as pneumonia, bacteremia and meningitis. One of the main forms of controlling pneumococcal infections was the development of vaccines based on the induction of antibodies against capsular polysaccharide (PS). Since a limited number of serotypes are included in pneumococcal conjugate vaccines (PCVs) and their effectiveness against non-invasive diseases is still controversial, the development of a new generation of serotype-independent vaccines is still a priority. Pneumococcal surface protein A (PspA) is an antigen with great potential for vaccine use. PspA shows some variability between strains and is divided in family 1 (clades 1 and 2), family 2 (clades 3, 4 and 5) and family 3 (clade 6). The aim of this work is to evaluate the immunogenicity and efficacy of poly (glycerol-adipate-coω-pentadecalactone) (PGA-co-PDL) nanoparticles (NPs) containing PspA (PspA4Pro) and formulated in micrometric particles (NP/NCMP PspA4Pro) in a murine model of pulmonary immunization. Initially, three inoculation techniques were tested for lung immunization of mice. Both the inoculation of the NP/NCMPs as dry powder using a pulmonary insufflator and inoculation of the resuspension of the NP/NCMPs in saline using a microsprayer did not induce IgG serum antibodies reproducibly. For the third immunization strategy, a micropipette was used for immunization through nasal instillation of two doses of the resuspension of the NP/NCMPs. Immunization with NP/NCMP PspA4Pro using this technique showed reproducible results, with the induction of anti-PspA4Pro IgG in serum and bronchoalveolar lavage (BALF). IgG antibodies induced by immunization with NP/NCMP PspA4Pro showed binding to the surface of intact bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding was observed for bacteria expressing PspA from clades 1 and 2 (family 1). Immunized mice were then challenged with strains ATCC6303 (serotype 3, PspA clade 5) or EF3030 (serotype 19F, PspA1) and BALF was collected after 12 and 24 hours, respectively. A reduction in bacterial load in BALF was observed in mice challenged with ATCC6303. A reduction in IL-6, TNF- KC/CXCL1 and MIP-2 CXCL2 levels in BALF of mice immunized with NP/NCMP PspA4Pro was also observed. Reduction in bacterial load was not observed for mice challenged with strain EF3030 though. A challenge with strain ATCC6303 strain was also performed to evaluate overall survival and partial protection was observed for the group immunized with NP/NCMP PspA4Pro. In conclusion, lung immunization with NP/NCMP PspA4Pro is able to induce antibodies in serum and lungs, conferring protection against a pneumococcal strain expressing PspA from the same family. Future studies are thus necessary to guarantee broader vaccine protection.

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Genomics, Genetic Variation, and Regions of Differences

Cited by 8 publications

References 136 publications

Highly Variable Streptococcus oralis Strains Are Common among Viridans Streptococci Isolated from Primates

Highly Variable Streptococcus oralis Strains Are Common among Viridans Streptococci Isolated from Primates

Streptococcus pneumoniae’s Virulence and Host Immunity: Aging, Diagnostics, and Prevention

Imunização pulmonar com nanopartículas contendo o antígeno PspA (Pneumococcal surface protein A)

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