Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • 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
Interplay between bacteria and host epithelial cells
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bacterial pathogens have developed multiple ways of manipulating host cell functions to exploit the host environment. We found that interactions with epithelial cells increase the resistance of the human pathogen Neisseria meningitidis to the antimicrobial peptide LL-37. This resistance was dependent on host cell cholesterol-rich microdomains and RhoA/Cdc42-dependent signalling.

At mucosal surfaces, pathogenic bacteria compete with the resident microbiota. Lactobacillus inhibits the adherence of a wide range of pathogens, however, the mechanisms of inhibition are still largely unknown. We demonstrate that certain lactobacilli interfere with host cell signalling pathways used by pathogenic bacteria during initial colonisation. Inhibitory lactobacilli blocked the pathogen-induced activation of Src, increases of host cytosolic [Ca2+] and upregulation of Egr1, in a TLR2-dependent fashion. We further identify Egr1 as a host factor crucial for efficient pathogen adherence. The pathogens used in these studies were N. meningitidis, Helicobacter pylori and Streptococcus pyogenes.

In summary, these studies highlight that the interplay between bacteria and host cells is a critical determinant of pathogenesis and bacterial co-existence in the host.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , 2013. , 96 p.
Keyword [en]
Microbial-cell interaction, Adherence, Infection, Lactic acid bacteria, Antimicrobial peptides
National Category
Microbiology
Research subject
Molecular Bioscience
Identifiers
URN: urn:nbn:se:su:diva-92692ISBN: 978-91-7447-735-1 (print)OAI: oai:DiVA.org:su-92692DiVA: diva2:640948
Public defence
2013-09-20, William-Olssonsalen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Epub ahead of print. Paper 3: Submitted. Paper 4: Manuscript.

Available from: 2013-08-29 Created: 2013-08-14 Last updated: 2013-08-19Bibliographically approved
List of papers
1. Endotoxin, capsule, and bacterial attachment contribute to Neisseria meningitidis resistance to the human antimicrobial peptide LL-37
Open this publication in new window or tab >>Endotoxin, capsule, and bacterial attachment contribute to Neisseria meningitidis resistance to the human antimicrobial peptide LL-37
2009 (English)In: Journal of Bacteriology, ISSN 0021-9193, E-ISSN 1098-5530, Vol. 191, no 12, 3861-3868 p.Article in journal (Refereed) Published
Abstract [en]

Pathogenic bacteria have evolved numerous mechanisms to evade the human immune system and have developed widespread resistance to traditional antibiotics. We studied the human pathogen Neisseria meningitidis and present evidence of novel mechanisms of resistance to the human antimicrobial peptide LL-37. We found that bacteria attached to host epithelial cells are resistant to 10 microM LL-37 whereas bacteria in solution or attached to plastic are killed, indicating that the cell microenvironment protects bacteria. The bacterial endotoxin lipooligosaccharide and the polysaccharide capsule contribute to LL-37 resistance, probably by preventing LL-37 from reaching the bacterial membrane, as more LL-37 reaches the bacterial membrane on both lipooligosaccharide-deficient and capsule-deficient mutants whereas both mutants are also more susceptible to LL-37 killing than the wild-type strain. N. meningitidis bacteria respond to sublethal doses of LL-37 and upregulate two of their capsule genes, siaC and siaD, which further results in upregulation of capsule biosynthesis.

National Category
Microbiology
Research subject
Molecular Bioscience
Identifiers
urn:nbn:se:su:diva-32385 (URN)10.1128/JB.01313-08 (DOI)000266454200011 ()19376861 (PubMedID)
Available from: 2009-12-09 Created: 2009-12-09 Last updated: 2017-12-12Bibliographically approved
2. Meningococcal resistance to antimicrobial peptides is mediated by bacterial adhesion and host cell RhoA and Cdc42 signalling
Open this publication in new window or tab >>Meningococcal resistance to antimicrobial peptides is mediated by bacterial adhesion and host cell RhoA and Cdc42 signalling
2013 (English)In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 15, no 11, 1938-1954 p.Article in journal (Refereed) Published
Abstract [en]

Antimicrobial peptides (AMPs) constitute an essential part of the innate immune defence. Pathogenic bacteria have evolved numerous strategies to withstand AMP-mediated killing. The influence of host epithelia on bacterial AMP resistance is, however, still largely unknown. We found that adhesion to pharyngeal epithelial cells protected Neisseria meningitidis, a leading cause of meningitis and sepsis, from the human cathelicidin LL-37, the cationic model amphipathic peptide (MAP) and the peptaibol alamethicin, but not from polymyxin B. Adhesion to primary airway epithelia resulted in a similar increase in LL-37 resistance. The inhibition of selective host cell signalling mediated by RhoA and Cdc42 was found to abolish the adhesion-induced LL-37 resistance by a mechanism unrelated to the actin cytoskeleton. Moreover, N. meningitidis triggered the formation of cholesterol-rich membrane microdomains in pharyngeal epithelial cells, and host cell cholesterol proved to be essential for adhesion-induced resistance. Our data highlight the importance of Rho GTPase-dependent host cell signalling for meningococcal AMP resistance. These results indicate that N. meningitidis selectively exploits the epithelial microenvironment in order to protect itself from LL-37.

National Category
Microbiology Cell and Molecular Biology
Research subject
Molecular Bioscience
Identifiers
urn:nbn:se:su:diva-92688 (URN)10.1111/cmi.12163 (DOI)000325541700012 ()
Note

AuthorCount: 4;

Available from: 2013-08-14 Created: 2013-08-14 Last updated: 2017-10-24Bibliographically approved
3. Lactobacillus inhibits host cell signalling used by pathogenic bacteria during initial colonization
Open this publication in new window or tab >>Lactobacillus inhibits host cell signalling used by pathogenic bacteria during initial colonization
Show others...
(English)Article in journal (Refereed) Submitted
National Category
Microbiology
Research subject
Molecular Bioscience
Identifiers
urn:nbn:se:su:diva-92689 (URN)
Available from: 2013-08-14 Created: 2013-08-14 Last updated: 2013-08-16Bibliographically approved
4. Lactobacillus inhibits Streptococcus pyogenes adherence by different antiadhesive properties
Open this publication in new window or tab >>Lactobacillus inhibits Streptococcus pyogenes adherence by different antiadhesive properties
(English)Manuscript (preprint) (Other academic)
National Category
Microbiology
Research subject
Molecular Bioscience
Identifiers
urn:nbn:se:su:diva-92690 (URN)
Available from: 2013-08-14 Created: 2013-08-14 Last updated: 2013-08-16Bibliographically approved
5. Lactobacilli reduce cell cytotoxicity caused by Streptococcus pyogenes by producing lactic acid that degrades the toxic component lipoteichoic acid
Open this publication in new window or tab >>Lactobacilli reduce cell cytotoxicity caused by Streptococcus pyogenes by producing lactic acid that degrades the toxic component lipoteichoic acid
2011 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 55, no 4, 1622-1628 p.Article in journal (Refereed) Published
Abstract [en]

Lactobacilli are known to prevent colonization by many pathogens; nevertheless, the mechanisms of their protective effect are largely unknown. In this work, we investigated the role of lactobacilli during infection of epithelial cells with group A streptococci (GAS). GAS cause a variety of illnesses ranging from noninvasive disease to more severe invasive infections, such as necrotizing fasciitis and toxic shock-like syndrome. Invasion of deeper tissues is facilitated by GAS-induced apoptosis and cell death. We found that lactobacilli inhibit GAS-induced host cell cytotoxicity and shedding of the complement regulator CD46. Further, survival assays demonstrated that lactic acid secreted by lactobacilli is highly bactericidal toward GAS. In addition, lactic acid treatment of GAS, but not heat killing, prior to infection abolishes the cytotoxic effects against human cells. Since lipoteichoic acid (LTA) of GAS is heat resistant and cytotoxic, we explored the effects of lactic acid on LTA. By applying such an approach, we demonstrate that lactic acid reduces epithelial cell damage caused by GAS by degrading both secreted and cell-bound LTA. Taken together, our experiments reveal a mechanism by which lactobacilli prevent pathogen-induced host cell damage.

National Category
Microbiology
Research subject
Molecular Bioscience
Identifiers
urn:nbn:se:su:diva-63672 (URN)10.1128/AAC.00770-10 (DOI)000288594600038 ()21245448 (PubMedID)
Available from: 2011-10-26 Created: 2011-10-26 Last updated: 2017-12-08Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Maudsdotter, Lisa
By organisation
Department of Molecular Biosciences, The Wenner-Gren Institute
Microbiology

Search outside of DiVA

GoogleGoogle Scholar

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 387 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • 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