umu.sePublikasjoner
Endre søk
Link to record
Permanent link

Direct link
BETA
Fahlgren, Anna
Publikasjoner (10 av 30) Visa alla publikasjoner
Taheri, N., Fällman, M., Wai, S. N. & Fahlgren, A. (2019). Accumulation of virulence-associated proteins in Campylobacter jejuni Outer Membrane Vesicles at human body temperature. Journal of Proteomics, 195, 33-40
Åpne denne publikasjonen i ny fane eller vindu >>Accumulation of virulence-associated proteins in Campylobacter jejuni Outer Membrane Vesicles at human body temperature
2019 (engelsk)Inngår i: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 195, s. 33-40Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Campylobacter jejuni is the major cause of bacterial gastroenteritis in humans. In contrast, colonization in avian hosts is asymptomatic. Body temperature differs between human (37 °C) and avian (42 °C) hosts, and bacterial growth in 37 °C is therefore a potential cue for higher virulence properties during human infection. The proteome of the bacteria was previously shown to be altered by temperature. Here we investigated whether temperature has an effect on the C. jejuni outer membrane vesicle (OMV) proteome, as OMVs are considered to be bacterial vehicles for protein delivery and might play a role during infection. OMVs isolated from C. jejuni strain 81-176 grown at 37 °C and 42 °C were analyzed by LC-ESI-MS/MS. 181 proteins were detected in both sample groups, one protein was exclusively present, and three were absent in OMVs from 37 °C. Of the 181 proteins, 59 were differentially expressed; 30 proteins were detected with higher abundance, and 29 proteins with lower abundance at 37 °C. Among the more highly abundant proteins, significantly more proteins were predicted to be associated with virulence. These data show that temperature has an impact on the property of the OMVs, and this might affect the outcome of colonization/infection by C. jejuni in different hosts.

Emneord
Campylobacter jejuni, OMVs, Proteomics, Temperature
HSV kategori
Forskningsprogram
mikrobiologi
Identifikatorer
urn:nbn:se:umu:diva-155499 (URN)10.1016/j.jprot.2019.01.005 (DOI)000459366000004 ()30641234 (PubMedID)
Tilgjengelig fra: 2019-01-18 Laget: 2019-01-18 Sist oppdatert: 2019-04-16bibliografisk kontrollert
Taheri, N., Mahmud, A. K., Sandblad, L., Fällman, M., Wai, S. N. & Fahlgren, A. (2018). Campylobacter jejuni bile exposure influences outer membrane vesicles protein content and bacterial interaction with epithelial cells. Scientific Reports, 8, Article ID 16996.
Åpne denne publikasjonen i ny fane eller vindu >>Campylobacter jejuni bile exposure influences outer membrane vesicles protein content and bacterial interaction with epithelial cells
Vise andre…
2018 (engelsk)Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 16996Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Campylobacter jejuni is a prevalent human pathogen and a major cause of bacterial gastroenteritis in the world. In humans, C. jejuni colonizes the intestinal tract and its tolerance to bile is crucial for bacteria to survive and establish infection. C. jejuni produces outer membrane vesicles (OMVs) which have been suggested to be involved in virulence. In this study, the proteome composition of C. jejuni OMVs in response to low concentration of bile was investigated. We showed that exposure of C. jejuni to low concentrations of bile, similar to the concentration in cecum, induced significant changes in the protein profile of OMVs released during growth without affecting the protein profile of the bacteria. This suggests that bile influences a selective packing of the OMVs after bacterial exposure to low bile. A low concentration of bile was found to increase bacterial adhesion to intestinal epithelial cells, likely by an enhanced hydrophobicity of the cell membrane following exposure to bile. The increased bacterial adhesiveness was not associated with increased invasion, instead bile exposure decreased C. jejuni invasion. OMVs released from bacteria upon exposure to low bile showed to increase both adhesion and invasion of non-bile-exposed bacteria into intestinal epithelial cells. These findings suggest that C. jejuni in environments with low concentrations of bile produce OMVs that facilitates colonization of the bacteria, and this could potentially contribute to virulence of C. jejuni in the gut.

sted, utgiver, år, opplag, sider
Nature Publishing Group, 2018
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-153787 (URN)10.1038/s41598-018-35409-0 (DOI)000450411700027 ()
Forskningsfinansiär
Carl Tryggers foundation
Tilgjengelig fra: 2018-12-03 Laget: 2018-12-03 Sist oppdatert: 2019-01-18bibliografisk kontrollert
Avican, U., Doruk, T., Östberg, Y., Fahlgren, A. & Forsberg, Å. (2017). The Tat substrate SufI is critical for the ability of Yersinia pseudotuberculosis to cause systemic infection. Infection and Immunity, 85(4), Article ID e00867-16.
Åpne denne publikasjonen i ny fane eller vindu >>The Tat substrate SufI is critical for the ability of Yersinia pseudotuberculosis to cause systemic infection
Vise andre…
2017 (engelsk)Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 85, nr 4, artikkel-id e00867-16Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The twin arginine translocation (Tat) system targets folded proteins across the inner membrane and is crucial for virulence in many important humanpathogenic bacteria. Tat has been shown to be required for the virulence of Yersinia pseudotuberculosis, and we recently showed that the system is critical for different virulence-related stress responses as well as for iron uptake. In this study, we wanted to address the role of the Tat substrates in in vivo virulence. Therefore, 22 genes encoding potential Tat substrates were mutated, and each mutant was evaluated in a competitive oral infection of mice. Interestingly, a.sufI mutant was essentially as attenuated for virulence as the Tat-deficient strain. We also verified that SufI was Tat dependent for membrane/periplasmic localization in Y. pseudotuberculosis. In vivo bioluminescent imaging of orally infected mice revealed that both the.sufI and Delta tatC mutants were able to colonize the cecum and Peyer's patches (PPs) and could spread to the mesenteric lymph nodes (MLNs). Importantly, at this point, neither the Delta tatC mutant nor the Delta sufI mutant was able to spread systemically, and they were gradually cleared. Immunostaining of MLNs revealed that both the Delta tatC and Delta sufI mutants were unable to spread from the initial infection foci and appeared to be contained by neutrophils, while wild-type bacteria readily spread to establish multiple foci from day 3 postinfection. Our results show that SufI alone is required for the establishment of systemic infection and is the major cause of the attenuation of the Delta tatC mutant.

Emneord
Yersinia pseudotuberculosis, Tat pathway, virulence, SufI, mesenteric lymph nodes, neutrophils
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-128087 (URN)10.1128/IAI.00867-16 (DOI)000397581800003 ()28115509 (PubMedID)
Tilgjengelig fra: 2016-11-22 Laget: 2016-11-22 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Wang, H., Avican, K., Fahlgren, A., Erttmann, S. F., Nuss, A. M., Dersch, P., . . . Wolf-Watz, H. (2016). Increased plasmid copy number is essential for Yersinia T3SS function and virulence. Science, 353(6298), 492-495
Åpne denne publikasjonen i ny fane eller vindu >>Increased plasmid copy number is essential for Yersinia T3SS function and virulence
Vise andre…
2016 (engelsk)Inngår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 353, nr 6298, s. 492-495Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Pathogenic bacteria have evolved numerous virulence mechanisms that are essential for establishing infections. The enterobacterium Yersinia uses a type III secretion system (T3SS) encoded by a 70-kilobase, low-copy, IncFII-class virulence plasmid. We report a novel virulence strategy in Y. pseudotuberculosis in which this pathogen up-regulates the plasmid copy number during infection. We found that an increased dose of plasmid-encoded genes is indispensable for virulence and substantially elevates the expression and function of the T3SS. Remarkably, we observed direct, tight coupling between plasmid replication and T3SS function. This regulatory pathway provides a framework for further exploration of the environmental sensing mechanisms of pathogenic bacteria.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-125586 (URN)10.1126/science.aaf7501 (DOI)000380583600042 ()27365311 (PubMedID)
Tilgjengelig fra: 2016-09-19 Laget: 2016-09-13 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Taheri, N., Fahlgren, A. & Fällman, M. (2016). Yersinia pseudotuberculosis Blocks Neutrophil Degranulation. Infection and Immunity, 84(12), 3369-3378
Åpne denne publikasjonen i ny fane eller vindu >>Yersinia pseudotuberculosis Blocks Neutrophil Degranulation
2016 (engelsk)Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 84, nr 12, s. 3369-3378Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Neutrophils are essential components of immunity and are rapidly recruited to infected or injured tissue. Upon their activation, neutrophils release granules to the cell's exterior, through a process called degranulation. These granules contain proteins with antimicrobial properties that help combat infection. The enteropathogenic bacterium Yersinia pseudotuberculosis successfully persists as an extracellular bacterium during infection by virtue of its translocation of virulence effectors (Yersinia outer proteins [Yops]) that act in the cytosol of host immune cells to subvert phagocytosis and proinflammatory responses. Here, we investigated the effect of Y. pseudotuberculosis on neutrophil degranulation upon cell contact. We found that virulent Y. pseudotuberculosis was able to prevent secondary granule release. The blocking effect was general, as the release of primary and tertiary granules was also reduced. Degranulation of secondary granules was also blocked in primed neutrophils, suggesting that this mechanism could be an important element of immune evasion. Further, wild-type bacteria conferred a transient block on neutrophils that prevented their degranulation upon contact with plasmid-cured, avirulent Y. pseudotuberculosis and Escherichia coli Detailed analyses showed that the block was strictly dependent on the cooperative actions of the two antiphagocytic effectors, YopE and YopH, suggesting that the neutrophil target structures constituting signaling molecules needed to initiate both phagocytosis and general degranulation. Thus, via these virulence effectors, Yersinia can impair several mechanisms of the neutrophil's antimicrobial arsenal, which underscores the power of its virulence effector machinery.

Emneord
Yersinia, neutrophil, degranulation
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-128892 (URN)10.1128/IAI.00760-16 (DOI)000390128700011 ()27620724 (PubMedID)
Tilgjengelig fra: 2016-12-19 Laget: 2016-12-19 Sist oppdatert: 2019-01-18bibliografisk kontrollert
Avican, K., Fahlgren, A., Huss, M., Heroven, A. K., Beckstette, M., Dersch, P. & Fällman, M. (2015). Reprogramming of Yersinia from Virulent to Persistent Mode Revealed by Complex In Vivo RNA-seq Analysis. PLoS Pathogens, 11(1), Article ID e1004600.
Åpne denne publikasjonen i ny fane eller vindu >>Reprogramming of Yersinia from Virulent to Persistent Mode Revealed by Complex In Vivo RNA-seq Analysis
Vise andre…
2015 (engelsk)Inngår i: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 11, nr 1, artikkel-id e1004600Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

We recently found that Yersinia pseudotuberculosis can be used as a model of persistent bacterial infections. We performed in vivo RNA-seq of bacteria in small cecal tissue biopsies at early and persistent stages of infection to determine strategies associated with persistence. Comprehensive analysis of mixed RNA populations from infected tissues revealed that Y. pseudotuberculosis undergoes transcriptional reprogramming with drastic down-regulation of T3SS virulence genes during persistence when the pathogen resides within the cecum. At the persistent stage, the expression pattern in many respects resembles the pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes and invA. These findings are expected to have impact on future rationales to identify suitable bacterial targets for new antibiotics. Other genes that are up-regulated during persistence are genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress, which indicates the influence of different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades influence the pattern of bacterial gene expression during persistence. Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our findings suggest a model for the life cycle of this enteropathogen with reprogramming from a virulent to an adapted phenotype capable of persisting and spreading by fecal shedding.

Emneord
Persistent infection, RNA-seq, PMNs, Yersinia, Transcriptome, wrba, fnr, rovA, arcA, rfaH
HSV kategori
Forskningsprogram
biologi, miljövetenskap
Identifikatorer
urn:nbn:se:umu:diva-100980 (URN)10.1371/journal.ppat.1004600 (DOI)000349106100030 ()25590628 (PubMedID)
Tilgjengelig fra: 2015-03-16 Laget: 2015-03-16 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Fahlgren, A., Avican, K., Westermark, L., Nordfelth, R. & Fällman, M. (2014). Colonization of cecum is important for development of persistent infection by Yersinia pseudotuberculosis. Infection and Immunity, 82(8), 3471-3482
Åpne denne publikasjonen i ny fane eller vindu >>Colonization of cecum is important for development of persistent infection by Yersinia pseudotuberculosis
Vise andre…
2014 (engelsk)Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 82, nr 8, s. 3471-3482Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Yersiniosis is a human disease caused by the bacterium Yersinia pseudotuberculosis or Yersinia enterocolitica. The infection is usually resolved but can lead to postinfectious sequelae, including reactive arthritis and erythema nodosum. The commonly used Yersinia mouse infection model mimics acute infection in humans to some extent but leads to systemic infection and eventual death. Here, we analyzed sublethal infection doses of Y. pseudotuberculosis in mice in real time using bioluminescent imaging and found that infections using these lower doses result in extended periods of asymptomatic infections in a fraction of mice. In a search for the site for bacterial persistence, we found that the cecum was the primary colonization site and was the site where the organism resided during a 115-day infection period. Persistent infection was accompanied by sustained fecal shedding of cultivable bacteria. Cecal patches were identified as the primary site for cecal colonization during persistence. Y. pseudotuberculosis bacteria were present in inflammatory lesions, in localized foci, or as single cells and also in neutrophil exudates in the cecal lumen. The chronically colonized cecum may serve as a reservoir for dissemination of infection to extraintestinal sites, and a chronic inflammatory state may trigger the onset of postinfectious sequelae. This novel mouse model for bacterial persistence in cecum has potential as an investigative tool to unveil a deeper understanding of bacterial adaptation and host immune defense mechanisms during persistent infection.

sted, utgiver, år, opplag, sider
American Society for Microbiology, 2014
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-91821 (URN)10.1128/IAI.01793-14 (DOI)000339161400035 ()
Tilgjengelig fra: 2014-09-01 Laget: 2014-08-18 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Normark, J., Nelson, M., Engström, P., Andersson, M., Björk, R., Moritz, T., . . . Bergström, S. (2014). Maladjusted Host Immune Responses Induce Experimental Cerebral Malaria-Like Pathology in a Murine Borrelia and Plasmodium Co-Infection Model. PLoS ONE, 9(7), Article ID e103295.
Åpne denne publikasjonen i ny fane eller vindu >>Maladjusted Host Immune Responses Induce Experimental Cerebral Malaria-Like Pathology in a Murine Borrelia and Plasmodium Co-Infection Model
Vise andre…
2014 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 7, artikkel-id e103295Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1 beta and TNF-alpha, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells.

sted, utgiver, år, opplag, sider
PLOS ONE, 2014
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-92942 (URN)10.1371/journal.pone.0103295 (DOI)000340028800036 ()
Tilgjengelig fra: 2014-09-17 Laget: 2014-09-09 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Westermark, L., Fahlgren, A. & Fällman, M. (2014). Yersinia pseudotuberculosis Efficiently Escapes Polymorphonuclear Neutrophils during Early Infection. Infection and Immunity, 82(3), 1181-1191
Åpne denne publikasjonen i ny fane eller vindu >>Yersinia pseudotuberculosis Efficiently Escapes Polymorphonuclear Neutrophils during Early Infection
2014 (engelsk)Inngår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 82, nr 3, s. 1181-1191Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The human-pathogenic species of the Gram-negative genus Yersinia preferentially target and inactivate cells of the innate immune defense, suggesting that this is a critical step by which these bacteria avoid elimination and cause disease. In this study, bacterial interactions with dendritic cells, macrophages, and polymorphonuclear neutrophils (PMNs) in intestinal lymphoid tissues during early Yersinia pseudotuberculosis infection were analyzed. Wild-type bacteria were shown to interact mainly with dendritic cells, but not with PMNs, on day 1 postinfection, while avirulent yopH and yopE mutants interacted with PMNs as well as with dendritic cells. To unravel the role of PMNs during the early phase of infection, we depleted mice of PMNs by using an anti-Ly6G antibody, after which we could see more-efficient initial colonization by the wild-type strain as well as by yopH, yopE, and yopK mutants on day 1 postinfection. Dissemination of yopH, yopE, and yopK mutants from the intestinal compartments to mesenteric lymph nodes was faster in PMN-depleted mice than in undepleted mice, emphasizing the importance of effective targeting of PMNs by these Yersinia outer proteins (Yops). In conclusion, escape from interaction with PMNs due to the action of YopH, YopE, and YopK is a key feature of pathogenic Yersinia species that allows colonization and effective dissemination.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-88290 (URN)10.1128/IAI.01634-13 (DOI)000333190900029 ()24379291 (PubMedID)
Tilgjengelig fra: 2014-05-02 Laget: 2014-04-29 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Antti, H., Fahlgren, A., Näsström, E., Kouremenos, K., Sundén-Cullberg, J., Guo, Y., . . . Fällman, M. (2013). Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance. PLoS ONE, 8(2), Article ID e56971.
Åpne denne publikasjonen i ny fane eller vindu >>Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance
Vise andre…
2013 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 2, artikkel-id e56971Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria. Methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) were used and for infecting mice, while natural MSSA infection was studied in humans. Samples of bacterial growth media, the blood of infected mice and of humans were analyzed with combined Gas Chromatography/Mass Spectrometry. Multivariate data analysis was used to reveal the metabolic profiles of infection and the responses to different antibiotic treatments. experiments resulted in the detection of 256 putative metabolites and mice infection experiments resulted in the detection of 474 putative metabolites. Importantly, ineffective and effective antibiotic treatments were differentiated already two hours after treatment start in both experimental systems. That is, the ineffective treatment of MRSA using cloxacillin and untreated controls produced one metabolic profile while all effective treatment combinations using cloxacillin or vancomycin for MSSA or MRSA produced another profile. For further evaluation of the concept, blood samples of humans admitted to intensive care with severe sepsis were analyzed. One hundred thirty-three putative metabolites differentiated severe MSSA sepsis (n = 6) from severe sepsis (n = 10) and identified treatment responses over time. Combined analysis of human, , and mice samples identified 25 metabolites indicative of effective treatment of sepsis. Taken together, this study provides a proof of concept of the utility of analyzing metabolite patterns in blood for early differentiation between ineffective and effective antibiotic treatment in acute infections.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-66816 (URN)10.1371/journal.pone.0056971 (DOI)000316849500048 ()23451124 (PubMedID)
Tilgjengelig fra: 2013-03-05 Laget: 2013-03-05 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Organisasjoner