| 1. |
- Brundin, Peik M.A., et al.
(författare)
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Blood hormones and torque teno virus in peripheral blood mononuclear cells
- 2020
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects (n = 27), we found presence of TTV in PMBC from 17.6% pre-MP (n = 17), 25.0% post-MP (n = 4) and 50.0% men (n = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.
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| 2. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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The human gut microbiome as a transporter of antibiotic resistance genes between continents
- 2015
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 59:10, s. 6551-6560
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.
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| 3. |
- Forsell, Joakim, et al.
(författare)
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The relation between Blastocystis and the intestinal microbiota in Swedish travellers
- 2017
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Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Blastocystis sp. is a unicellular eukaryote that is commonly found in the human intestine. Its ability to cause disease is debated and a subject for ongoing research. In this study, faecal samples from 35 Swedish university students were examined through shotgun metagenomics before and after travel to the Indian peninsula or Central Africa. We aimed at assessing the impact of travel on Blastocystis carriage and seek associations between Blastocystis and the bacterial microbiota.Results: We found a prevalence of Blastocystis of 16/35 (46%) before travel and 15/35 (43%) after travel. The two most commonly Blastocystis subtypes (STs) found were ST3 and ST4, accounting for 20 of the 31 samples positive for Blastocystis. No mixed subtype carriage was detected. All ten individuals with a typable ST before and after travel maintained their initial ST. The composition of the gut bacterial community was not significantly different between Blastocystis-carriers and non-carriers. Interestingly, the presence of Blastocystis was accompanied with higher abundances of the bacterial genera Sporolactobacillus and Candidatus Carsonella. Blastocystis carriage was positively associated with high bacterial genus richness, and negatively correlated to the Bacteroides-driven enterotype. These associations were both largely dependent on ST4 – a subtype commonly described from Europe – while the globally prevalent ST3 did not show such significant relationships.Conclusions: The high rate of Blastocystis subtype persistence found during travel indicates that long-term carriage of Blastocystis is common. The associations between Blastocystis and the bacterial microbiota found in this study could imply a link between Blastocystis and a healthy microbiota as well as with diets high in vegetables. Whether the associations between Blastocystis and the microbiota are resulting from the presence of Blastocystis, or are a prerequisite for colonization with Blastocystis, are interesting questions for further studies.
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| 4. |
- Claesson, Rolf, et al.
(författare)
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Characterization of Aggregatibacter actinomycetemcomitans Serotype b Strains with Five Different, Including Two Novel, Leukotoxin Promoter Structures
- 2020
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Ingår i: Vaccines. - Basel, Switzerland : MDPI. - 2076-393X. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- The JP2 genotype of A. actinomycetemcomitans, serotype b has attracted much interest during the past three decades due to its close association with periodontitis in young individuals and the enhanced expression of a leukotoxin (LtxA). A typical feature of this genotype is a 530-base pair (bp) deletion in the ltxCABD promoter region controlling leukotoxin expression. In the present work, we have characterized serotype b strains with four additional promoter types. Two novel types have been recognized, that is, one with a 230-bp deletion and one with a 172-bp duplication. Moreover, a strain with a 640-bp deletion and three strains with a full-length promoter, including the type strain Y4, were included in the present study. The seven strains were characterized by multi locus sequence typing (MLST) and arbitrarily primed polymerase chain reaction (PCR) and assessed for LtxA production. MLST showed that the strains with the non-JP2-like deletions represented distinct monophyletic groups, whereas the JP2 strain, HK1651, represented a separate branch. LtxA production was high in all three strains with a promoter deletion, whereas the other four strains showed significantly lower levels. It can be concluded that the genetic characterization and determination of LtxA production of A. actinomycetemcomitans isolates from individuals with periodontitis can contribute to the identification of novel virulent genotypes of this bacterium.
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| 5. |
- Hernandez, Jorge, et al.
(författare)
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Globally disseminated human pathogenic Escherichia coli of O25b-ST131 clone, harbouring blaCTX-M-15, found in Glaucous-winged gull at remote Commander Islands, Russia
- 2010
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Ingår i: Environmental Microbiology Reports. - : Wiley. - 1758-2229. ; 2:2, s. 329-332
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Tidskriftsartikel (refereegranskat)abstract
- With focus on environmental dissemination of antibiotic resistance among clinically relevant bacteria, such as the rising ESBL type of resistance among Escherichia coli, we investigated antibiotic resistance levels in wild birds in the Commander Islands and Kamchatka, Russia. Despite overall low resistance levels in randomly selected E. coli (one from each sample), we found multi-resistant ESBL-producing E. coli harbouring bla(CTX-M-14) and bla(CTX-M-15) using selective screening. Among these multi-resistant ESBL-producing E. coli we found one bla(CTX-M-15) harbouring strain belonging to the O25b-ST131 clone, recognized for its clonal disseminated worldwide as a human pathogen. The potential in acquiring resistant bacteria of human origin, especially highly pathogenic clones, as well as downstream consequences of that, should not be underestimated but further investigated.
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| 6. |
- Rydén, Patrik, 1969-, et al.
(författare)
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Outbreaks of tularemia in a boreal forest region depends on mosquito prevalence
- 2012
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 205:2, s. 297-304
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Tidskriftsartikel (refereegranskat)abstract
- Background. We aimed to evaluate the potential association of mosquito prevalence in a boreal forest area with transmission of the bacterial disease tularemia to humans, and model the annual variation of disease using local weather data.Methods. A prediction model for mosquito abundance was built using weather and mosquito catch data. Then a negative binomial regression model based on the predicted mosquito abundance and local weather data was built to predict annual numbers of humans contracting tularemia in Dalarna County, Sweden.Results. Three hundred seventy humans were diagnosed with tularemia between 1981 and 2007, 94% of them during 7 summer outbreaks. Disease transmission was concentrated along rivers in the area. The predicted mosquito abundance was correlated (0.41, P < .05) with the annual number of human cases. The predicted mosquito peaks consistently preceded the median onset time of human tularemia (temporal correlation, 0.76; P < .05). Our final predictive model included 5 environmental variables and identified 6 of the 7 outbreaks.Conclusions. This work suggests that a high prevalence of mosquitoes in late summer is a prerequisite for outbreaks of tularemia in a tularemia-endemic boreal forest area of Sweden and that environmental variables can be used as risk indicators.
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| 7. |
- Vahvelainen, Nelli, et al.
(författare)
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Pilus PilA of the naturally competent HACEK group pathogen Aggregatibacter actinomycetemcomitans stimulates human leukocytes and interacts with both DNA and proinflammatory cytokines
- 2022
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Ingår i: Microbial Pathogenesis. - : Elsevier. - 0882-4010 .- 1096-1208. ; 173:Part A
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Tidskriftsartikel (refereegranskat)abstract
- Each HACEK group pathogen, which can cause infective endocarditis, expresses type IVa pili. The type IVa major pilin PilA plays a role in bacterial colonization, virulence, twitching motility, and the uptake of extracellular DNA. The type IV prepilin homolog PilA of the periodontal pathogen A. actinomycetemcomitans (AaPilA) is linked to DNA uptake and natural competence.Our aim was to investigate the virulence properties and immunogenic potential of AaPilA. Since Neisseria meningitidis PilE, which shares sequence similarity with AaPilA, participates in sequestering host cytokines, we examined the ability of AaPilA to interact with various cytokines. Moreover, we investigated the structural characteristics of AaPilA with molecular modeling.AaPilA was conserved among A. actinomycetemcomitans strains. One of the 18 different natural variants, PilAD7S, is present in naturally competent strains. This variant interacted with DNA and bound interleukin (IL)-8 and tumor necrosis factor (TNF)-α. Specific anti-AaPilA antibodies were present in A. actinomycetemcomitans-positive periodontitis patient sera, and the production of reactive oxygen species from human neutrophils was less effectively induced by the ΔpilA mutant than by the wild-type strains. However, AaPilA did not stimulate human macrophages to produce proinflammatory cytokines, nor was it cytotoxic.The results strengthen our earlier hypothesis that the DNA uptake machinery of A. actinomycetemcomitans is involved in the sequestration of inflammatory cytokines. Furthermore, AaPilA stimulates host immune cells, such as B cells and neutrophils, making it a potential virulence factor.
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| 8. |
- Antti, Henrik, et al.
(författare)
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Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Angelin, Martin, 1976-
(författare)
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Travel – a risk factor for disease and spread of antibiotic resistance
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As international travel is rapidly increasing, more people are being exposed to potentially more antibiotic resistant bacteria, a changed infectious disease epidemiology, and an increased risk of accidents and crime. Research-based advice is needed to adequately inform travellers about these risks. We studied travellers who sought advice from the Travel Medicine Clinic at the Department of Infectious Diseases, Umeå University Hospital, as well as university students from Umeå, Stockholm, and Gothenburg travelling abroad for study, research, and clinical exchange programs.From retrospective data at the Travel Medicine Clinic, we found that pre-existing health problems were rare among travellers from Umeå seeking pre- travel health advice and vaccinations. In addition, we found that the travel destination and the sex of the traveller affected vaccination levels. Although hepatitis A is endemic to both Thailand and Turkey, compared to travellers to Thailand few travellers to Turkey visited the clinic for hepatitis A vaccination. The data also revealed that more women than men were vaccinated against Japanese encephalitis despite comparable trips.A prospective survey study showed that travellers felt that the pre-travel health advice they received was helpful. Two-thirds of the travellers followed the advice given although they still fell ill to the same extent as those who were not compliant with the advice. Factors outside the control of travellers likely affect the travel-related morbidity. Compared to older travellers, younger travellers were less compliant with advice, fell ill to a greater extent, and took greater risks during travel.In a prospective survey study, we found that healthcare students had higher illness rates and risk exposure when abroad compared to students from other disciplines. This difference was mainly due to the fact that healthcare students more often travelled to developing regions during their study period abroad. When abroad, half of all students increased their alcohol consumption and this was linked to an increased risk of theft and higher likelihood of meeting a new sex partner.The healthcare students participating in the survey study also submitted stool samples before and after travel. These samples were tested for the presence of antibiotic resistance, both by selective culturing for ESBL-PE (Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae) as well as by metagenomic sequencing. About one-third (35%) of the students became colonised by ESBL-PE following their study abroad. The strongest risk factor for colonisation was travel destination; for example, 70% of students who had travelled to India became colonised. Antibiotic treatment during travel was also a significant risk factor for colonisation.The stool samples from a subset of study subjects were analysed using metagenomic sequencing. From this we learned that although the majority of resistance genes in the gut microbiome remained unchanged following travel, several clinically important resistance genes increased, most prominently genes encoding resistance to sulphonamide, trimethoprim, and beta-lactams. Overall, taxonomic changes associated with travel were small but the proportion of Proteobacteria, which includes several clinically important bacteria (e.g., Enterobacteriaceae), increased in a majority of the study subjects.Clearly, there are risks associated with international travel and these risks include outside factors as well as the personal behaviour of travellers. We believe our results can be used to develop better pre-travel advice for tourists as well as university students studying abroad resulting in safer travel.
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| 10. |
- Svärd, Anna, et al.
(författare)
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Presence and immunoreactivity of Aggregatibacter actinomycetemcomitans in rheumatoid arthritis
- 2024
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Ingår i: Pathogens. - : MDPI. - 2076-0817. ; 13:5, s. 368-368
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Tidskriftsartikel (refereegranskat)abstract
- The presence of periodontal pathogens is associated with an increased prevalence of rheumatoid arthritis (RA). The systemic antibody response to epitopes of these bacteria is often used asa proxy to study correlations between bacteria and RA. The primary aim of the present study is toexamine the correlation between the presence of Aggregatibacter actinomycetemcomitans (Aa) in theoral cavity and serum antibodies against the leukotoxin (LtxA) produced by this bacterium. Thesalivary presence of Aa was analyzed with quantitative PCR and serum LtxA ab in a cell culturebased neutralization assay. The analyses were performed on samples from a well-characterized RAcohort (n = 189) and a reference population of blood donors (n = 101). Salivary Aa was present in15% of the RA patients and 6% of the blood donors. LtxA ab were detected in 19% of RA-sera andin 16% of sera from blood donors. The correlation between salivary Aa and serum LtxA ab wassurprisingly low (rho = 0.55 [95% CI: 0.40, 0.68]). The presence of salivary Aa showed no significantassociation with any of the RA-associated parameters documented in the cohort. A limitation of thepresent study is the relatively low number of individuals with detectable concentrations of Aa insaliva. Moreover, in the comparison of detectable Aa prevalence between RA patients and blooddonors, we assumed that the two groups were equivalent in other Aa prognostic factors. These limitations must be taken into consideration when the result from the study is interpreted. We concludethat a systemic immune response to Aa LtxA does not fully reflect the prevalence of Aa in saliva. Inaddition, the association between RA-associated parameters and the presence of Aa was negligiblein the present RA cohort.
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