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Andersson, ChristopherORCID iD iconorcid.org/0000-0001-5702-9742
Publications (7 of 7) Show all publications
Quereda, J. J., Andersson, C., Cossart, P., Johansson, J. & Pizarro-Cerda, J. (2018). Role in virulence of phospholipases, listeriolysin O and listeriolysin S from epidemic Listeria monocytogenes using the chicken embryo infection model. Veterinary research (Print), 49, Article ID 13.
Open this publication in new window or tab >>Role in virulence of phospholipases, listeriolysin O and listeriolysin S from epidemic Listeria monocytogenes using the chicken embryo infection model
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2018 (English)In: Veterinary research (Print), ISSN 0928-4249, E-ISSN 1297-9716, Vol. 49, article id 13Article in journal (Refereed) Published
Abstract [en]

Most human listeriosis outbreaks are caused by Listeria monocytogenes evolutionary lineage I strains which possess four exotoxins: a phosphatidylinositol-specific phospholipase C (PlcA), a broad-range phospholipase C (PlcB), listeriolysin O (LLO) and listeriolysin S (LLS). The simultaneous contribution of these molecules to virulence has never been explored. Here, the importance of these four exotoxins of an epidemic lineage I L. monocytogenes strain (F2365) in virulence was assessed in chicken embryos infected in the allantoic cavity. We show that LLS does not play a role in virulence while LLO is required to infect and kill chicken embryos both in wild type transcriptional regulator of virulence PrfA -(PrfAWT) and constitutively active PrfA (PrfA*) backgrounds. We demonstrate that PlcA, a toxin previously considered as a minor virulence factor, played a major role in virulence in a PrfA* background. Interestingly, GFP transcriptional fusions show that the plcA promoter is less active than the hly promoter in vitro, explaining why the contribution of PlcA to virulence could be observed more importantly in a PrfA* background. Together, our results suggest that PlcA might play a more important role in the infectious lifecycle of L. monocytogenes than previously thought, explaining why all the strains of L. monocytogenes have conserved an intact copy of plcA in their genomes.

Place, publisher, year, edition, pages
BioMed Central, 2018
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-145143 (URN)10.1186/s13567-017-0496-4 (DOI)000424675000001 ()29409521 (PubMedID)
Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2018-06-09Bibliographically approved
Good, J. A. D., Andersson, C., Hansen, S., Wall, J., Krishnan, S., Begum, A., . . . Johansson, J. (2016). Attenuating Listeria monocytogenes virulence by targeting the regulatory protein PrfA. Cell chemical biology, 23(3), 404-414
Open this publication in new window or tab >>Attenuating Listeria monocytogenes virulence by targeting the regulatory protein PrfA
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2016 (English)In: Cell chemical biology, ISSN 2451-9448, Vol. 23, no 3, p. 404-414Article in journal (Refereed) Published
Abstract [en]

The transcriptional activator PrfA, a member of the Crp/Fnr family, controls the expression of some key virulence factors necessary for infection by the human bacterial pathogen Listeria monocytogenes. Phenotypic screening identified ring-fused 2-pyridone molecules that at low micromolar concentrations attenuate L. monocytogenes infectivity by reducing the expression of virulence genes, without compromising bacterial growth. These inhibitors bind the transcriptional regulator PrfA and decrease its affinity for the consensus DNA binding site. Structural characterization of this interaction revealed that one of the ring-fused 2-pyridones, compound 1, binds within a hydrophobic pocket, located between the C- and N-terminal domains of PrfA, and interacts with residues important for PrfA activation. This indicates that these inhibitors maintain the DNA-binding helix-turn-helix motif of PrfA in a disordered state, thereby preventing a PrfA:DNA interaction. Ring-fused 2-pyridones represent a new class of chemical probes for studying virulence in L. monocytogenes.

National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:umu:diva-114083 (URN)10.1016/j.chembiol.2016.02.013 (DOI)000381508300013 ()26991105 (PubMedID)
Note

Originally published in manuscipt form in thesis.

Available from: 2016-01-12 Created: 2016-01-12 Last updated: 2018-06-07Bibliographically approved
Andersson, C. (2016). Regulatory pathways and virulence inhibition in Listeria monocytogenes. (Doctoral dissertation). Umeå: Umeå Universitet
Open this publication in new window or tab >>Regulatory pathways and virulence inhibition in Listeria monocytogenes
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Listeria monocytogenes is a rod-shaped Gram positive bacterium. It generally exist ubiquitously in nature, where it lives as a saprophyte. Occasionally it however enters the food chain, from where it can be ingested by humans and cause gastro-intestinal distress. In immunocompetent individuals L. monocytogenes is generally cleared within a couple of weeks, but in immunocompromised patients it can progress to listeriosis, a potentially life-threatening infection in the central nervous system. If the infected individual is pregnant, the bacteria can cross the placental barrier and infect the fetus, possibly leading to spontaneous abortion.

The infectivity of L. monocytogenes requires a certain set of genes, and the majority of them is dependent on the transcriptional regulator PrfA. The expression and activity of PrfA is controlled at several levels, and has traditionally been viewed to be active at 37 °C (virulence conditions) where it bind as a homodimer to a “PrfA-box” and induces the expression of the downstream gene.

One of these genes is ActA, which enables intracellular movement by recruiting an actin polymerizing protein complex. When studying the effects of a blue light receptor we surprisingly found an effect of ActA at non-virulent conditions, where it is required for the bacteria to properly react to light exposure.

To further study the PrfA regulon we tested deletion mutants of several PrfA-regulated virulence genes in chicken embryo infection studies. Based on these studies we could conclude that the chicken embryo model is a viable complement to traditional murine models, especially when investigating non-traditional internalin pathogenicity pathways. We have also studied the effects of small molecule virulence inhibitors that, by acting on PrfA, can inhibit L. monocytogenes infectivity in cell cultures with concentrations in the low micro-molar range.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2016. p. 37
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1772
Keywords
Listeria monocytogenes, PrfA, ActA, infection
National Category
Cell and Molecular Biology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:umu:diva-114085 (URN)978-91-7601-397-7 (ISBN)
Public defence
2016-02-04, KB3B1, KBC-huset, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2016-01-14 Created: 2016-01-12 Last updated: 2018-06-07Bibliographically approved
Andersson, C., Gripenland, J. & Johansson, J. (2015). Using the chicken embryo to assess virulence of Listeria monocytogenes and to model other microbial infections. Nature Protocols, 10(8), 1155-1164
Open this publication in new window or tab >>Using the chicken embryo to assess virulence of Listeria monocytogenes and to model other microbial infections
2015 (English)In: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 10, no 8, p. 1155-1164Article in journal (Refereed) Published
Abstract [en]

Microbial infections are a global health problem, particularly as microbes are continually developing resistance to antimicrobial treatments. An effective and reliable method for testing the virulence of different microbial pathogens is therefore a useful research tool. This protocol describes how the chicken embryo can be used as a trustworthy, inexpensive, ethically desirable and quickly accessible model to assess the virulence of the human bacterial pathogen Listeria monocytogenes, which can also be extended to other microbial pathogens. We provide a step-by-step protocol and figures and videos detailing the method, including egg handling, infection strategies, pathogenicity screening and isolation of infected organs. From the start of incubation of the fertilized eggs, the protocol takes <4 weeks to complete, with the infection part taking only 3 d. We discuss the appropriate controls to use and potential adjustments needed for adapting the protocol for other microbial pathogens.

Place, publisher, year, edition, pages
Nature Publishing Group, 2015
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-107282 (URN)10.1038/nprot.2015.073 (DOI)000358482200003 ()26134955 (PubMedID)
Available from: 2015-08-31 Created: 2015-08-21 Last updated: 2018-06-07Bibliographically approved
Gripenland, J., Andersson, C. & Johansson, J. (2014). Exploring the chicken embryo as a possible model for studying Listeria monocytogenes pathogenicity. Frontiers in Cellular and Infection Microbiology, 4, Article ID 170.
Open this publication in new window or tab >>Exploring the chicken embryo as a possible model for studying Listeria monocytogenes pathogenicity
2014 (English)In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 4, article id 170Article in journal (Refereed) Published
Abstract [en]

Listeria monocytogenes is a bacterial pathogen capable of causing severe infections in humans, often with fatal outcomes. Many different animal models exist to study L. monocytogenes pathogenicity, and we have investigated the chicken embryo as an infection model: What are the benefits and possible drawbacks? We have compared a defined wild-type strain with its isogenic strains lacking well-characterized virulence factors. Our results show that wild-type L. monocytogenes, already at a relatively low infection dose (similar to 5 x 10(2) cfu), caused death of the chicken embryo within 36 h, in contrast to strains lacking the main transcriptional activator of virulence, PrfA, or the cytolysin LLO. Surprisingly, strains lacking the major adhesins InIA and InIB caused similar mortality as the wild-type strain. In conclusion, our results suggest that the chicken embryo is a practical model to study L. monocytogenes infections, especially when analyzing alternative virulence pathways independent of the InIA and InIB adhesins. However, the route of infection might be different from a human infection. The chicken embryo model and other Listeria infection models are discussed.

Keywords
Listeria monocytogenes, chicken embryo, PrfA, virulence: InIA, LLO, InIB
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-100984 (URN)10.3389/fcimb.2014.00170 (DOI)000349152600003 ()25540772 (PubMedID)
Available from: 2015-03-16 Created: 2015-03-16 Last updated: 2018-06-07Bibliographically approved
Tiensuu, T., Andersson, C., Ryden, P. & Johansson, J. (2013). Cycles of light and dark co-ordinate reversible colony differentiation in Listeria monocytogenes. Molecular Microbiology, 87(4), 909-924
Open this publication in new window or tab >>Cycles of light and dark co-ordinate reversible colony differentiation in Listeria monocytogenes
2013 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 87, no 4, p. 909-924Article in journal (Refereed) Published
Abstract [en]

Recently, several light receptors have been identified in non-phototrophic bacteria, but their physiological roles still remain rather elusive. Here we show that colonies of the saprophytic bacterium Listeria monocytogenes undergo synchronized multicellular behaviour on agar plates, in response to oscillating light/dark conditions, giving rise to alternating ring formation (opaque and translucent rings). On agar plates, bacteria from opaque rings survive increased levels of reactive oxygen species (ROS), as well as repeated cycles of light and dark, better than bacteria from translucent rings. The ring formation is strictly dependent on a blue-light receptor, Lmo0799, acting through the stress-sigma factor, sigma B. A transposon screening identified 48 mutants unable to form rings at alternating light conditions, with several of them showing a decreased sigma B activity/level. However, some of the tested mutants displayed a varied sigma B activity depending on which of the two stress conditions tested (light or H2O2 exposure). Intriguingly, the transcriptional regulator PrfA and the virulence factor ActA were shown to be required for ring formation by a mechanism involving activation of sigma B. All in all, this suggests a distinct pathway for Lmo0799 that converge into a common signalling pathway for sigma B activation. Our results show that night and day cycles co-ordinate a reversible differentiation of a L.monocytogenes colony at room temperature, by a process synchronized by a blue-light receptor and sigma B.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-67399 (URN)10.1111/mmi.12140 (DOI)000314925700015 ()
Available from: 2013-04-09 Created: 2013-03-18 Last updated: 2018-06-08Bibliographically approved
Gripenland, J., Andersson, C. & Johansson, J.Evaluating the chicken embryo as a model for studying Listeria monocytogenes pathogenesis: a role for the PrfA pathway.
Open this publication in new window or tab >>Evaluating the chicken embryo as a model for studying Listeria monocytogenes pathogenesis: a role for the PrfA pathway
(English)Manuscript (preprint) (Other academic)
National Category
Basic Medicine Microbiology
Identifiers
urn:nbn:se:umu:diva-55425 (URN)
Available from: 2012-05-14 Created: 2012-05-14 Last updated: 2018-06-08Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5702-9742

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