his.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Modeling the regulation of the competence-evoking quorum sensing network in Streptococcus pneumoniae
University of Skövde, School of Life Sciences.
University of Skövde, School of Life Sciences.
University of Skövde, School of Life Sciences.
Swedish Institute for Infectious Disease Control, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Show others and affiliations
2007 (English)In: Biosystems (Amsterdam. Print), ISSN 0303-2647, E-ISSN 1872-8324, Vol. 90, no 1, 211-223 p.Article in journal (Refereed) Published
Abstract [en]

Competence for genetic transformation seems to play a fundamental role in the biology of Streptococcus pneumoniae and is believed to account for serotype switching, evolution of virulence factors, and rapid emergence of antibiotic resistance. The initiation of competence is regulated by the quorum sensing system referred as the ComABCDE pathway. Experimental studies reveal that competence is down-regulated a short time after its induction and several hypotheses about the mechanism(s) responsible for this shut-down have been presented. Possibly, a ComX-dependent gene product, such as a repressor or a phosphatase, is involved. To better understand the down-regulation of the competence-evoking system in S. pneumoniae, a mathematical model was set up. By analyzing the model, we suggest that shut-down of competence possibly occurs at the transcriptional level on the comCDE operon. As a result of introducing a putative comX-dependent repressor, which inhibits expression of comCDE and comX, in the mathematical model, competence is demonstrated to appear in waves. This is supported by experimental studies showing the appearance of successive competence cycles in pneumococcal batch cultures.

Place, publisher, year, edition, pages
Elsevier, 2007. Vol. 90, no 1, 211-223 p.
Identifiers
URN: urn:nbn:se:his:diva-1887DOI: 10.1016/j.biosystems.2006.08.005ISI: 000248966800019PubMedID: 17011700Scopus ID: 2-s2.0-34447093989OAI: oai:DiVA.org:his-1887DiVA: diva2:32163
Available from: 2007-09-19 Created: 2007-09-19 Last updated: 2014-10-24Bibliographically approved
In thesis
1. Studies on emergence and spread of antibiotic resistant Streptococcus pneumoniae
Open this publication in new window or tab >>Studies on emergence and spread of antibiotic resistant Streptococcus pneumoniae
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Streptococcus pneumoniae is one of the major contributors to mortality and morbidity around  the  world.  It  causes  a  wide  variety  of  diseases  ranging  from  uncomplicated respiratory  infections  to  life-threatening  invasive  infections  such  as  meningitis  and septicemia. In recent years, the effectiveness of antibiotic therapy has been hampered by  the  increasing  rates  of  resistant  pneumococci.  As  antibiotic  resistance  increases, there is a growing need for interventions that minimize opportunities for development and spread  of resistant  pneumococci.  The aim  of this  thesis  was  to learn  more  about emergence  and  spread  of  antibiotic  resistant  pneumococci  using  both  theoretical  and empirical methods.  Since the increasing prevalence of resistant pneumococci is mainly due to the spread of strains belonging to few clones, interventions for controlling pneumococcal transmission  in  the  community  were  studied.  Model  predictions  suggested  that interventions for efficiently control organism transmission should include reduction of group sizes in the day-care centers. Simulations also indicated that it appears extremely difficult  to  reduce  the  rates  of  penicillin  non-susceptible  pneumococci  by  simply decreasing  the  penicillin  consumption  assumed  that  reduced  penicillin  susceptibility does not imply a fitness cost for the organism. Managing the penicillin resistance rates in pneumococci then probably requires a more restrictive use of penicillin together with other  control  measures  such  as  vaccine  programs.  Although  clonal  spread  is  the primary  mechanism  for  the  rapid  emergence  of  resistance  in  pneumococci,  natural competence  for  genetic  transformation  also  seems  to  be  involved.  Further  molecular understanding  of competence regulation  is  important  to be  able  to prevent  horizontal spread  of  resistance  genes.  Studying  the  competence  regulation  by  theoretical  means led  to  the  conclusion  that  down-regulation  of  competence  is  probably  caused  by  a repressor acting on the comCDE operon at the level of transcription.  Despite the globally emerging frequency of resistant pneumococci, we conclude in a prospective study that antimicrobial resistance in invasive pneumococci in south-west Sweden remains limited. Any correlations between resistance pattern and clinical parameters could not be revealed. However, the serotype distribution was observed to differ  between  strains  with  reduced  susceptibility  and  fully  susceptible  strains  as isolates  with  decreased  susceptibility  more  frequently  belonged  to  the  serotypes included in the 7-valent vaccine.

Place, publisher, year, edition, pages
Stockholm: Karolinska Institutet, 2010. 82 p.
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-4699 (URN)978-91-7457-027-4 (ISBN)
Funder
Knowledge Foundation
Available from: 2011-04-27 Created: 2011-02-01 Last updated: 2014-10-24Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Karlsson, DianaKarlsson, StefanGustafsson, ErikNilsson, Patric
By organisation
School of Life Sciences
In the same journal
Biosystems (Amsterdam. Print)

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 1576 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf