| 1. |
- de Klerk, Nele, et al.
(författare)
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Lactobacilli Reduce Helicobacter pylori Attachment to Host Gastric Epithelial Cells by Inhibiting Adhesion Gene Expression
- 2016
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 84:5, s. 1526-1535
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Tidskriftsartikel (refereegranskat)abstract
- The human gastrointestinal tract, including the harsh environment of the stomach, harbors a large variety of bacteria, of which Lactobacillus species are prominent members. The molecular mechanisms by which species of lactobacilli interfere with pathogen colonization are not fully characterized. In this study, we aimed to study the effect of lactobacillus strains upon the initial attachment of Helicobacter pylori to host cells. Here we report a novel mechanism by which lactobacilli inhibit adherence of the gastric pathogen H. pylori. In a screen with Lactobacillus isolates, we found that only a few could reduce adherence of H. pylori to gastric epithelial cells. Decreased attachment was not due to competition for space or to lactobacillus-mediated killing of the pathogen. Instead, we show that lactobacilli act on H. pylori directly by an effector molecule that is released into the medium. This effector molecule acts on H. pylori by inhibiting expression of the adhesin-encoding gene sabA. Finally, we verified that inhibitory lactobacilli reduced H. pylori colonization in an in vivo model. In conclusion, certain Lactobacillus strains affect pathogen adherence by inhibiting sabA expression and thereby reducing H. pylori binding capacity.
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| 2. |
- de Klerk, Nele, et al.
(författare)
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The Host Cell Transcription Factor EGR1 Is Induced by Bacteria through the EGFR-ERK1/2 Pathway
- 2017
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The essential first step in bacterial colonization is adhesion to the host epithelial cells. The early host-responses post-bacterial adhesions are still poorly understood. Early growth response 1 (EGR1) is an early response transcriptional regulator that can be rapidly induced by various environmental stimuli. Several bacteria can induce EGR1 expression in host cells, but the involved bacterial characteristics and the underlying molecular mechanisms of this response are largely unknown. Here, we show that EGR1 can be induced in host epithelial cells by different species of bacteria independent of the adherence level, Gram-staining type and pathogenicity. However, bacterial viability and contact with host cells is necessary, indicating that an active interaction between bacteria and the host is important. Furthermore, the strongest response is observed in cells originating from the natural site of the infection, suggesting that the EGR1 induction is cell type specific. Finally, we show that EGFRERK1/2 and beta 1-integrin signaling are the main pathways used for bacteria-mediated EGR1 upregulation. In conclusion, the increase of EGR1 expression in epithelial cells is a common stress induced, cell type specific response upon host-bacteria interaction that is mediated by EGFRERK1/2 and beta 1-integrin signaling.
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| 3. |
- Eriksson, Jens, et al.
(författare)
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Characterization of motility and piliation in pathogenic Neisseria
- 2015
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Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The type IV pili (Tfp) of pathogenic Neisseria (i. e., N. gonorrhoeae and N. meningitidis) are essential for twitching motility. Tfp retraction, which is dependent on the ATPase PilT, generates the forces that move bacteria over surfaces. Neisseria motility has mainly been studied in N. gonorrhoeae whereas the motility of N. meningitidis has not yet been characterized. Results: In this work, we analyzed bacterial motility and monitored Tfp retraction using live- cell imaging of freely moving bacteria. We observed that N. meningitidis moved over surfaces at an approximate speed of 1.6 mu m/s, whereas N. gonorrhoeae moved with a lower speed (1.0 mu/s). An alignment of the meningococcal and gonococcal pilT promoters revealed a conserved single base pair variation in the -10 promoter element that influence PilT expression. By tracking mutants with altered pilT expression or pilE sequence, we concluded that the difference in motility speed was independent of both. Live-cell imaging using total internal reflection fluorescence microscopy demonstrated that N. gonorrhoeae more often moved with fewer visible retracting filaments when compared to N. meningitidis. Correspondingly, meningococci also displayed a higher level of piliation in transmission electron microscopy. Nevertheless, motile gonococci that had the same number of filaments as N. meningitidis still moved with a lower speed. Conclusions: These data reveal differences in both speed and piliation between the pathogenic Neisseria species during twitching motility, suggesting a difference in Tfp-dynamics.
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| 4. |
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| 5. |
- Geörg, Miriam, et al.
(författare)
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Meningococcal resistance to antimicrobial peptides is mediated by bacterial adhesion and host cell RhoA and Cdc42 signalling
- 2013
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 15:11, s. 1938-1954
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Jones, Allison, et al.
(författare)
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Endotoxin, capsule, and bacterial attachment contribute to Neisseria meningitidis resistance to the human antimicrobial peptide LL-37
- 2009
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Ingår i: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 191:12, s. 3861-3868
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
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| 8. |
- Maudsdotter, Lisa, 1984-
(författare)
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Interplay between bacteria and host epithelial cells
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 9. |
- Maudsdotter, Lisa, 1984-, et al.
(författare)
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Lactobacilli reduce cell cytotoxicity caused by Streptococcus pyogenes by producing lactic acid that degrades the toxic component lipoteichoic acid
- 2011
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 55:4, s. 1622-1628
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
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