Andreas Albert Matussek

• Ögren, Jessica; Henningsson, Anna J.; Botero-Kleiven, Silvia; Matussek, Andreas Albert & Wilhelmsson, Peter (2026). Prevalence of Enterocytozoon bieneusi and Encephalitozoon spp. in Swedish patients with suspected gastrointestinal parasite infection: a cross-sectional molecular study. European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. doi: 10.1007/s10096-026-05443-2. Fulltekst i vitenarkiv
• Bai, Xiangning; Rayner, Simon; Skuggen, Linda Ellevog; Engseth, Kine; Bjørnstad, Pål Marius & Dalland, Marianne [Vis alle 9 forfattere av denne artikkelen] (2025). A preliminary evaluation of a fast, low-cost, and high-throughput nucleic acid extraction method for bacterial microbiota profiling in low-microbial biomass samples. Scientific Reports. 15(1). doi: 10.1038/s41598-024-84682-9. Fulltekst i vitenarkiv Vis sammendrag

  The respiratory tract is colonized with low-density microbial communities, which have been shown to impact human respiratory health through microbiota–host interactions. However, a lack of fast and cost-effective nucleic acid extraction method for low-microbial biomass samples hinders investigation of respiratory microbiota. Here, we performed a pilot study to assess the suitability of the NAxtra nucleic acid extraction protocol for profiling bacterial microbiota in respiratory samples. A small number of nasopharyngeal aspirate (n = 8), nasal swab (n = 8), and saliva samples (n = 8) were collected, nucleic acids were isolated using the NAxtra protocol, and 16 S rRNA gene sequencing was performed to characterize bacterial microbiota, which were compared to the same sample types from previous studies using other protocols. The bacterial composition in nasal and saliva samples were consistent with previous reports. Saliva microbiota was significantly richer than nasal microbiota and varied less among individual samples than nasal microbiota. Bacterial composition in nasal samples was distinct from nasopharyngeal aspirates, but closer to saliva samples. A sequencing depth of 50,000 reads/sample was sufficient for microbiota profiling in low biomass respiratory samples. Our pilot study indicates the potential of the NAxtra protocol for bacterial microbiota characterization of low-microbial biomass samples and supports a more comprehensive study to fully evaluate the value of the NAxtra protocol in microbiota research and clinical diagnostics of respiratory pathogens.

• Wang, Lei; Huang, Ying; Bai, Xiangning; Zhang, Ji; Mernelius, Sara & Chromek, Milan [Vis alle 9 forfattere av denne artikkelen] (2024). Prevalence and Characteristics of Plasmid-Encoded Serine Protease EspP in Clinical Shiga Toxin-Producing Escherichia coli Strains from Patients in Sweden. Microorganisms. 12(3), s. 1–10. doi: 10.3390/microorganisms12030589. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin-producing Escherichia coli (STEC) infection can cause a broad spectrum of symptoms spanning from asymptomatic shedding to mild and bloody diarrhea (BD) and even life-threatening hemolytic-uremic syndrome (HUS). As a member of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, EspP has the ability to degrade human coagulation factor V, leading to mucosal bleeding, and also plays a role in bacteria adhesion to the surface of host cells. Here, we investigated the prevalence and genetic diversity of espP among clinical STEC isolates from patients with mild diarrhea, BD, and HUS, as well as from asymptomatic individuals, and assessed the presence of espP and its subtypes in correlation to disease severity. We found that 130 out of 239 (54.4%) clinical STEC strains were espP positive, and the presence of espP was significantly associated with BD, HUS, and O157:H7 serotype. Eighteen unique espP genotypes (GTs) were identified and categorized into four espP subtypes, i.e., espPα (119, 91.5%), espPγ (5, 3.8%), espPδ (4, 3.1%), and espPε (2, 1.5%). espPα was widely distributed, especially in strains from patients with BD and HUS, and correlated with serotype O157:H7. Serogroup O26, O145, O121, and O103 strains carried espPα only. Ten GTs were identified in espPα, and espPα/GT2 was significantly associated with severe disease, i.e., BD and HUS. Additionally, espP was strongly linked to the presence of eae gene, and the coexistence of espPα and stx2/stx2a + stx2c was closely related to HUS status. To sum up, our data demonstrated a high prevalence and genetic diversity of the espP gene in clinical STEC strains in Sweden and revealed an association between the presence of espP, espP subtypes, and disease severity. espP, particularly the espPα subtype, was prone to be present in more virulent STEC strains, e.g., “top-six” serotypes strains.

• Debelius, Justine W.; Engstrand, Lars; Matussek, Andreas Albert; Brusselaers, Nele; Morton, James T. & Stenmarker, Margaretha [Vis alle 7 forfattere av denne artikkelen] (2023). The Local Tumor Microbiome Is Associated with Survival in Late-Stage Colorectal Cancer Patients. Microbiology spectrum. 11(3), s. 1–13. doi: 10.1128/spectrum.05066-22. Fulltekst i vitenarkiv Vis sammendrag

  The gut microbiome is associated with survival in colorectal cancer. Single organisms have been identified as markers of poor prognosis. However, in situ imaging of tumors demonstrate a polymicrobial tumor-associated community. To understand the role of these polymicrobial communities in survival, we conducted a nested case-control study in late-stage cancer patients undergoing resection for primary adenocarcinoma. The microbiome of paired tumor and adjacent normal tissue samples was profiled using 16S rRNA sequencing. We found a consistent difference in the microbiome between paired tumor and adjacent tissue, despite strong individual microbial identities. Furthermore, a larger difference between normal and tumor tissue was associated with prognosis: patients with shorter survival had a larger difference between normal and tumor tissue. Within the tumor tissue, we identified a 39-member community statistic associated with survival; for every log2-fold increase in this value, an individual’s odds of survival increased by 20% (odds ratio survival 1.20; 95% confidence interval = 1.04 to 1.33). Our results suggest that a polymicrobial tumor-specific microbiome is associated with survival in late-stage colorectal cancer patients.

• Wang, Lei; Bai, Xiangning; Ylinen, Elisa; Zhang, Ji; Saxén, Harri & Matussek, Andreas Albert (2023). Genetic Characterization of Intimin Gene (eae) in Clinical Shiga Toxin-Producing Escherichia coli Strains from Pediatric Patients in Finland. Toxins. 15(12), s. 1–10. doi: 10.3390/toxins15120669. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin (Stx)-producing Escherichia coli (STEC) infections cause outbreaks of severe disease in children ranging from bloody diarrhea to hemolytic uremic syndrome (HUS). The adherent factor intimin, encoded by eae, can facilitate the colonization process of strains and is frequently associated with severe disease. The purpose of this study was to examine and analyze the prevalence and polymorphisms of eae in clinical STEC strains from pediatric patients under 17 years old with and without HUS, and to assess the pathogenic risk of different eae subtypes. We studied 240 STEC strains isolated from pediatric patients in Finland with whole genome sequencing. The gene eae was present in 209 (87.1%) strains, among which 49 (23.4%) were from patients with HUS, and 160 (76.6%) were from patients without HUS. O157:H7 (126, 60.3%) was the most predominant serotype among eae-positive STEC strains. Twenty-three different eae genotypes were identified, which were categorized into five eae subtypes, i.e., γ1, β3, ε1, θ and ζ3. The subtype eae-γ1 was significantly overrepresented in strains from patients aged 5–17 years, while β3 and ε1 were more commonly found in strains from patients under 5 years. All O157:H7 strains carried eae-γ1; among non-O157 strains, strains of each serotype harbored one eae subtype. No association was observed between the presence of eae/its subtypes and HUS. However, the combination of eae-γ1+stx2a was significantly associated with HUS. In conclusion, this study demonstrated a high occurrence and genetic variety of eae in clinical STEC from pediatric patients under 17 years old in Finland, and that eae is not essential for STEC-associated HUS. However, the combination of certain eae subtypes with stx subtypes, i.e., eae-γ1+stx2a, may be used as risk predictors for the development of severe disease in children.

• Matussek, Andreas Albert; Mernelius, Sara; Chromek, Milan; Zhang, Ji; Frykman, Anne & Hansson, Sverker [Vis alle 9 forfattere av denne artikkelen] (2023). Genome-wide association study of hemolytic uremic syndrome causing Shiga toxin-producing Escherichia coli from Sweden, 1994–2018. European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. 42(6), s. 771–779. doi: 10.1007/s10096-023-04600-1. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Shiga toxin-producing Esc herichia coli (STEC) infection can cause clinical manifestations ranging from diarrhea to potentially fatal hemolytic uremic syndrome (HUS). This study is aimed at identifying STEC genetic factors associated with the development of HUS in Sweden. A total of 238 STEC genomes from STEC-infected patients with and without HUS between 1994 and 2018 in Sweden were included in this study. Serotypes, Shiga toxin gene ( stx ) subtypes, and virulence genes were characterized in correlation to clinical symptoms (HUS and non-HUS), and pan-genome wide association study was performed. Sixty-five strains belonged to O157:H7, and 173 belonged to non-O157 serotypes. Our study revealed that strains of O157:H7 serotype especially clade 8 were most commonly found in patients with HUS in Sweden. stx2a and stx2a  +  stx2c subtypes were significantly associated with HUS. Other virulence factors associated with HUS mainly included intimin ( eae ) and its receptor ( tir ), adhesion factors, toxins, and secretion system proteins. Pangenome wide-association study identified numbers of accessory genes significantly overrepresented in HUS-STEC strains, including genes encoding outer membrane proteins, transcriptional regulators, phage-related proteins, and numerous genes related to hypothetical proteins. Whole-genome phylogeny and multiple correspondence analysis of pangenomes could not differentiate HUS-STEC from non-HUS-STEC strains. In O157:H7 cluster, strains from HUS patients clustered closely; however, no significant difference in virulence genes was found in O157 strains from patients with and without HUS. These results suggest that STEC strains from different phylogenetic backgrounds may independently acquire genes determining their pathogenicity and confirm that other non-bacterial factors and/or bacteria-host interaction may affect STEC pathogenesis.

• Yang, Xi; Liu, Qian; Bai, Xiangning; Hu, Bin; Jiang, Deshui & Jiao, Hongbo [Vis alle 11 forfattere av denne artikkelen] (2022). High Prevalence and Persistence of Escherichia coli Strains Producing Shiga Toxin Subtype 2k in Goat Herds. Microbiology spectrum. 10:e0157122(4), s. 1–12. doi: 10.1128/spectrum.01571-22. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin (Stx)-producing Escherichia coli (STEC) is a zoonotic pathogen with the ability to cause severe diseases like hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is the key virulence factor in STEC and can be classified into two types, Stx1 and Stx2, and different subtypes. Stx2k is a newly reported Stx2 subtype in E. coli strains from diarrheal patients, animals, and raw meats exclusively in China so far. To understand the reservoir of Stx2k-producing E. coli (Stx2k-STEC), we investigated Stx2k-STEC strains in goat herds and examined their genetic characteristics using whole-genome sequencing. A total of 448 STEC strains were recovered from 2,896 goat fecal samples, and 37.95% (170/448) were Stx2k-STEC. Stx2k-STEC strains of serotype O93:H28 and sequence type 4038 (ST4038) were the most predominant and were detected over several years. Notably, 55% of Stx2k-STEC strains carried the heat-labile toxin (LT)-encoding gene (elt) defining enterotoxigenic E. coli (ETEC), thereby exhibiting the hybrid STEC/ETEC pathotype. Stx2k-converting prophage genomes clustered into four groups and exhibited high similarity within each group. Strains from patients, raw meat, sheep, and goats were intermixed distributed in the phylogenetic tree, indicating the risk for cross-species spread of Stx2k-STEC and pathogenic potential for humans. Further studies are required to investigate the Stx2k-STEC strains in other reservoirs and to understand the mechanism of persistence in these hosts.

• Magnusson, Cecilia; Mernelius, Sara; Bengnér, Malin; Norén, Torbjörn; Serrander, Lena & Forshell, Sophie [Vis alle 7 forfattere av denne artikkelen] (2022). Characterization of a Clostridioides difficile outbreak caused by PCR ribotype 046, associated with increased mortality. Emerging microbes & infections. 11(1), s. 850–859. doi: 10.1080/22221751.2022.2049981. Fulltekst i vitenarkiv Vis sammendrag

  This study describes a large nosocomial outbreak of Clostridioides difficile infections (CDI) dominated by ribotype (RT) 046 in a Swedish hospital. The present study aimed to examine the pathogenicity of this RT, explore epidemiological links by whole genome sequencing (WGS), and evaluate different interventions implemented to stop the outbreak. Clinical isolates (n =  366) collected during and after the outbreak were ribotyped and 246 isolates were subjected to WGS. Medical records of patients infected with the seven most common RTs were evaluated. RT046 was spread effectively throughout the hospital and was the most common among the 44 different RTs found (114/366 isolates). Infection with RT046 was associated with higher mortality compared to other strains (20.2% to 7.8%), although there were no differences in concomitant disease, age or antibiotic treatment. To control the outbreak, several measures were successfully implemented.

• Viprey, Virginie F.; Davis, Georgina L.; Benson, Anthony D.; Ewin, Duncan; Spittal, William & Vernon, Jon J. [Vis alle 28 forfattere av denne artikkelen] (2022). A point-prevalence study on community and inpatient Clostridioides difficile infections (CDI): results from Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI), July to November 2018. Eurosurveillance. ISSN 1025-496X. 27(26), s. 1–13. doi: 10.2807/1560-7917.ES.2022.27.26.2100704. Fulltekst i vitenarkiv Vis sammendrag

  Background There is a paucity of data on community-based Clostridioides difficile infection (CDI) and how these compare with inpatient CDI. Aim To compare data on the populations with CDI in hospitals vs the community across 12 European countries. Methods For this point-prevalence study (July–November 2018), testing sites sent residual diagnostic material on sampling days to a coordinating laboratory for CDI testing and PCR ribotyping (n = 3,163). Information on whether CDI testing was requested at the original site was used to identify undiagnosed CDI. We used medical records to identify differences between healthcare settings in patient demographics and risk factors for detection of C. difficile with or without free toxin. Results The CDI positivity rate was 4.4% (country range: 0–16.2) in hospital samples, and 1.3% (country range: 0–2.2%) in community samples. The highest prevalence of toxinotype IIIb (027, 181 and 176) was seen in eastern European countries (56%; 43/77), the region with the lowest testing rate (58%; 164/281). Different predisposing risk factors were observed (use of broad-spectrum penicillins in the community (OR: 8.09 (1.9–35.6), p = 0.01); fluoroquinolones/cephalosporins in hospitals (OR: 2.2 (1.2–4.3), p = 0.01; OR: 2.0 (1.1–3.7), p = 0.02)). Half of community CDI cases were undetected because of absence of clinical suspicion, accounting for three times more undiagnosed adults in the community compared with hospitals (ca 111,000 vs 37,000 cases/year in Europe). Conclusion These findings support recommendations for improving diagnosis in patients presenting with diarrhoea in the community, to guide good practice to limit the spread of CDI.

• Bai, Xiangning; Ylinen, Elisa; Zhang, Ji; Salmenlinna, Saara; Halkilahti, Jani & Saxen, Harri [Vis alle 9 forfattere av denne artikkelen] (2022). Comparative Genomics of Shiga Toxin-Producing Escherichia coli Strains Isolated from Pediatric Patients with and without Hemolytic Uremic Syndrome from 2000 to 2016 in Finland. Microbiology spectrum. 10(4). doi: 10.1128/spectrum.00660-22. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin-producing Escherichia coli (STEC) infection can cause mild to severe illness, such as nonbloody or bloody diarrhea, and the fatal hemolytic uremic syndrome (HUS). The molecular mechanism underlying the variable pathogenicity of STEC infection is not fully defined so far. Here, we performed a comparative genomics study on a large collection of clinical STEC strains collected from STEC-infected pediatric patients with and without HUS in Finland over a 16-year period, aiming to identify the bacterial genetic factors that can predict the risk to cause HUS and poor renal outcome. Of 240 STEC strains included in this study, 52 (21.7%) were from pediatric patients with HUS. Serotype O157:H7 was the main cause of HUS, and Shiga toxin gene subtype stx2a was significantly associated with HUS. Comparative genomics and pangenome-wide association studies identified a number of virulence and accessory genes overrepresented in HUS-associated STEC compared to non-HUS STEC strains, including genes encoding cytolethal distending toxins, type III secretion system effectors, adherence factors, etc. No virulence or accessory gene was significantly associated with risk factors for poor renal outcome among HUS patients assessed in this study, including need for and duration of dialysis, presence and duration of anuria, and leukocyte counts. Whole-genome phylogeny and multiple-correspondence analysis of pangenomes could not separate HUS STEC from non-HUS STEC strains, suggesting that STEC strains with diverse genetic backgrounds may independently acquire genetic elements that determine their varied pathogenicity. Our findings indicate that nonbacterial factors, i.e., characteristics of the host immunity, might affect STEC virulence and clinical outcomes.

• Yang, Xi; Liu, Qian; Sun, Hui; Xiong, Yanwen; Matussek, Andreas Albert & Bai, Xiangning (2022). Genomic Characterization of Escherichia coli O8 Strains Producing Shiga Toxin 2l Subtype. Microorganisms. 10(6). doi: 10.3390/microorganisms10061245. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin-producing Escherichia coli (STEC) can cause diseases ranging from mild diarrhea to fatal extra-intestinal hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is the key virulence factor in STEC, two Stx types (Stx1 and Stx2) and several subtypes varying in sequences, toxicity, and host specificity have been identified. Stx2l is a newly-designated subtype related to human disease but lacks thorough characterization. Here, we identified Stx2l from five STEC strains (Stx2l-STECs) recovered from raw mutton and beef in China. Whole-genome sequencing (WGS) was used to characterize the Stx2l-STECs in this study together with Stx2l-STECs retrieved from public databases. Our study revealed that all the analyzed Stx2l-STEC strains belonged to the same serogroup O8. Multilocus sequencing typing (MLST) showed two sequence types (ST88 and ST23) among these strains. Stx2l-converting prophages from different sources shared a highly similar structure and sequence. Single-nucleotide polymorphism (SNP)-based analysis revealed genetic relatedness between the human-derived and food-derived strains belonging to ST23. To conclude, our study supported the designation of Stx2l and demonstrated diverse host range and geographical distribution of Stx2l-STECs.Stx2l-STEC strains from different sources showed a high genetic similarity with an identical O8 serogroup. Further studies are needed to investigate the epidemiological trait and pathogenic potential of Stx2l-STEC strains.

• Hua, Ying; Zhang, Ji; Jernberg, Cecilia; Chromek, Milan; Hansson, Sverker & Frykman, Anne [Vis alle 10 forfattere av denne artikkelen] (2021). Molecular characterization of the enterohemolysin gene (ehxA) in clinical Shiga toxin-producing Escherichia coli isolates. Toxins. 13:71(1), s. 1–11. doi: 10.3390/toxins13010071. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin (Stx)-producing Escherichia coli (STEC) is an important foodborne pathogen with the ability to cause bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Little is known about enterohemolysin-encoded by ehxA. Here we investigated the prevalence and diversity of ehxA in 239 STEC isolates from human clinical samples. In total, 199 out of 239 isolates (83.26%) were ehxA positive, and ehxA was significantly overrepresented in isolates carrying stx2a + stx2c (p < 0.001) and eae (p < 0.001). The presence of ehxA was significantly associated with BD and serotype O157:H7. Five ehxA subtypes were identified, among which, ehxA subtypes B, C, and F were overrepresented in eae-positive isolates. All O157:H7 isolates carried ehxA subtype B, which was related to BD and HUS. Three ehxA groups were observed in the phylogenetic analysis, namely, group Ⅰ (ehxA subtype A), group Ⅱ (ehxA subtype B, C, and F), and group Ⅲ (ehxA subtype D). Most BD- and HUS-associated isolates were clustered into ehxA group Ⅱ, while ehxA group Ⅰ was associated with non-bloody stool and individuals ≥10 years of age. The presence of ehxA + eae and ehxA + eae + stx2 was significantly associated with HUS and O157:H7 isolates. In summary, this study showed a high prevalence and the considerable genetic diversity of ehxA among clinical STEC isolates. The ehxA genotypes (subtype B and phylogenetic group Ⅱ) could be used as risk predictors, as they were associated with severe clinical symptoms, such as BD and HUS. Furthermore, ehxA, together with stx and eae, can be used as a risk predictor for HUS in STEC infections.

• Lager, Malin; Wilhelmsson, Peter; Matussek, Andreas Albert; Lindgren, Per-Eric & Henningsson, Anna J. (2021). Molecular Detection of Borrelia Bacteria in Cerebrospinal Fluid-Optimisation of Pre-Analytical Sample Handling for Increased Analytical Sensitivity. Diagnostics (Basel). 11:2088(11), s. 1–16. doi: 10.3390/diagnostics11112088. Fulltekst i vitenarkiv Vis sammendrag

  The main tools for clinical diagnostics of Lyme neuroborreliosis (LNB) are based on serology, i.e., detection of antibodies in cerebrospinal fluid (CSF). In some cases, PCR may be used as a supplement, e.g., on CSF from patients with early LNB. Standardisation of the molecular methods and systematic evaluation of the pre-analytical handling is lacking. To increase the analytical sensitivity for detection of Borrelia bacteria in CSF by PCR targeting the 16S rRNA gene, parameters were systematically evaluated on CSF samples spiked with a known amount of cultured Borrelia bacteria. The results showed that the parameters such as centrifugation time and speed, the use of complementary DNA as a template (in combination with primers and a probe aiming at target gene 16S rRNA), and the absence of inhibitors (e.g., erythrocytes) had the highest impact on the analytical sensitivity. Based on these results, a protocol for optimised handling of CSF samples before molecular analysis was proposed. However, no clinical evaluation of the proposed protocol has been done so far, and further investigations of the diagnostic sensitivity need to be performed on well-characterised clinical samples from patients with LNB.

• Yang, Xi; Wu, Yannong; Liu, Qian; Sun, Hui; Luo, Ming & Xiong, Yanwen [Vis alle 9 forfattere av denne artikkelen] (2021). Genomic Characteristics of Stx2e-Producing Escherichia coli Strains Derived from Humans, Animals, and Meats. Pathogens. ISSN 2076-0817. 10(12). doi: 10.3390/pathogens10121551. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin (Stx) can be classified into two types, Stx1 and Stx2, and different subtypes. Stx2e is a subtype commonly causing porcine edema disease and rarely reported in humans. The purpose of this study was to analyze the prevalence and genetic characteristics of Stx2e-producing Escherichia coli (Stx2e-STEC) strains from humans compared to strains from animals and meats in China. Stx2e-STEC strains were screened from our STEC collection, and whole-genome sequencing was performed to characterize their genetic features. Our study showed a wide distribution of Stx2e-STEC among diverse hosts and a higher proportion of Stx2e-STEC among human STEC strains in China. Three human Stx2e-STEC isolates belonged to O100:H30, Onovel26:H30, and O8:H9 serotypes and varied in genetic features. Human Stx2e-STECs phylogenetically clustered with animal- and food-derived strains. Stx2e-STEC strains from animals and meat showed multidrug resistance, while human strains were only resistant to azithromycin and tetracycline. Of note, a high proportion (55.9%) of Stx2e-STEC strains, including one human strain, carried the heat-stable and heat-labile enterotoxin-encoding genes st and lt, exhibiting a STEC/enterotoxigenic E. coli (ETEC) hybrid pathotype. Given that no distinct genetic feature was found in Stx2e-STEC strains from different sources, animal- and food-derived strains may pose the risk of causing human disease.

• Bai, Xiangning; Zhang, Ji; Hua, Ying; Jernberg, Cecilia; Xiong, Yanwen & French, Nigel [Vis alle 11 forfattere av denne artikkelen] (2021). Genomic insights into clinical Shiga toxin-producing Escherichia coli strains: A 15-year period survey in Jönköping, Sweden. Frontiers in Microbiology. 12. doi: 10.3389/fmicb.2021.627861. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin-producing Escherichia coli (STEC) are important foodborne pathogens that can cause human infections ranging from asymptomatic carriage to bloody diarrhea (BD) and fatal hemolytic uremic syndrome (HUS). However, the molecular mechanism of STEC pathogenesis is not entirely known. Here, we demonstrated a large scale of molecular epidemiology and in-depth genomic study of clinical STEC isolates utilizing clinical and epidemiological data collected in Region Jönköping County, Sweden, over a 15-year period. Out of 184 STEC isolates recovered from distinct patients, 55 were from patients with BD, and 129 were from individuals with non-bloody stools (NBS). Five individuals developed HUS. Adults were more associated with BD. Serotypes O157:H7, O26:H11, O103:H2, O121:H19, and O104:H4 were more often associated with BD. The presence of Shiga toxin-encoding gene subtypes stx 2a , stx 2a + stx 2c , and stx 1a + stx 2c was associated with BD, while stx 1 a was associated with milder disease. Multiplex virulence and accessory genes were correlated with BD; these genes encode toxins, adhesion, autotransporters, invasion, and secretion system. A number of antimicrobial resistance (AMR) genes, such as aminoglycoside, aminocoumarin, macrolide, and fluoroquinolone resistance genes, were prevalent among clinical STEC isolates. Whole-genome phylogeny revealed that O157 and non-O157 STEC isolates evolved from distinct lineages with a few exceptions. Isolates from BD showed more tendency to cluster closely. In conclusion, this study unravels molecular trait of clinical STEC strains and identifies genetic factors associated with severe clinical outcomes, which could contribute to management of STEC infections and disease progression if confirmed by further functional validation.

• Hua, Ying; Chromek, Milan; Frykman, Anne; Jernberg, Cecilia; Georgieva, Valya & Hansson, Sverker [Vis alle 11 forfattere av denne artikkelen] (2021). Whole-genome characterization of hemolytic uremic syndrome-causing Shiga toxin-producing Escherichia coli in Sweden. Virulence. ISSN 2150-5594. 12(1), s. 1296–1305. doi: 10.1080/21505594.2021.1922010. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin-producing Escherichia coli, a foodborne bacterial pathogen, has been linked to a broad spectrum of clinical outcomes ranging from asymptomatic carriage to fatal hemolytic uremic syndrome (HUS). Here, we collected clinical data and STEC strains from HUS patients from 1994 through 2018, whole-genome sequencing was performed to molecularly characterize HUS-associated STEC strains, statistical analysis was conducted to identify bacterial genetic factors associated with severe outcomes in HUS patients. O157:H7 was the most predominant serotype (57%) among 54 HUS-associated STEC strains, followed by O121:H19 (19%) and O26:H11 (7%). Notably, some non-predominant serotypes such as O59:H17 (2%) and O109:H21 (2%) also caused HUS. All O157:H7 strains with one exception belonged to clade 8. During follow-up at a median of 4 years, 41% of the patients had renal sequelae. Fifty-nine virulence genes were found to be statistically associated with severe renal sequelae, these genes encoded type II and type III secretion system effectors, chaperones, and other factors. Notably, virulence genes associated with severe clinical outcomes were significantly more prevalent in O157:H7 strains. In contrast, genes related to mild symptoms were evenly distributed across all serotypes. The whole-genome phylogeny indicated high genomic diversity among HUS-STEC strains. No distinct cluster was found between HUS and non-HUS STEC strains. The current study showed that O157:H7 remains the main cause of STEC-associated HUS, despite the rising importance of other non-O157 serotypes. Besides, O157:H7 is associated with severe renal sequelae in the follow-up, which could be a risk factor for long-term prognosis in HUS patients.

• Yang, Xi; Sun, Hui; Fan, Ruyue; Fu, Shanshan; Zhang, Ji & Matussek, Andreas [Vis alle 8 forfattere av denne artikkelen] (2020). Genetic diversity of the intimin gene (eae) in non-O157 Shiga toxin-producing Escherichia coli strains in China. Scientific Reports. 10. doi: 10.1038/s41598-020-60225-w. Fulltekst i vitenarkiv
• Ylinen, Elisa; Salmenlinna, Saara; Halkilahti, Jani; Jahnukainen, Timo; Korhonen, Linda & Virkkala, Tila [Vis alle 15 forfattere av denne artikkelen] (2020). Hemolytic uremic syndrome caused by Shiga toxin–producing Escherichia coli in children: incidence, risk factors, and clinical outcome. Pediatric nephrology (Berlin, West). ISSN 0931-041X. 35, s. 1749–1759. doi: 10.1007/s00467-020-04560-0. Fulltekst i vitenarkiv
• Ögren, Jessica; Dienus, Olaf; Beser, Jessica; Henningsson, Anna J. & Matussek, Andreas (2020). Protozoan infections are under-recognized in Swedish patients with gastrointestinal symptoms. European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. 39(11), s. 2153–2160. doi: 10.1007/s10096-020-03974-w. Fulltekst i vitenarkiv
• Hua, Ying; Bai, Xiangning; Zhang, Ji; Jernberg, Cecilia; Chromek, Milan & Hansson, Sverker [Vis alle 11 forfattere av denne artikkelen] (2020). Molecular characteristics of eae-positive clinical Shiga toxin-producing Escherichia coli in Sweden. Emerging microbes & infections. 9(1), s. 2562–2570. doi: 10.1080/22221751.2020.1850182. Fulltekst i vitenarkiv Vis sammendrag

  Shiga toxin (Stx)-producing Escherichia coli (STEC) can cause a wide range of symptoms from asymptomatic carriage, mild diarrhea to bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Intimin, encoded by the eae gene, also plays a critical role in STEC pathogenesis. Herein, we investigated the prevalence and genetic diversity of eae among clinical STEC isolates from patients with diarrhea, BD, HUS as well as from asymptomatic STEC-positive individuals in Sweden with whole-genome sequencing. We found that 173 out of 239 (72.4%) of clinical STEC strains were eae positive. Six eae subtypes (ϵ1, γ1, β3, θ, ζ and ρ) were identified eae and its subtype γ1 were significantly overrepresented in O157:H7 strains isolated from BD and HUS patients. ϵ1 was associated with O121:H19 and O103:H2 strains, and β3 to O26:H11 strains. The combination of eae subtype γ1 and stx subtype (stx 2 or stx 1+stx 2) is more likely to cause severe disease, suggesting the possibility of using eae genotypes in risk assessment of STEC infection. In summary, this study demonstrated a high prevalence of eae in clinical STEC strains and considerable genetic diversity of eae in STEC strains in Sweden from 1994 through 2018, and revealed association between eae subtypes and disease severity.

• Lager, Malin; Dessau, Ram B.; Wilhelmsson, Peter; Nyman, Dag; Jensen, Guro Furset & Matussek, Andreas [Vis alle 8 forfattere av denne artikkelen] (2019). Serological diagnostics of Lyme borreliosis: comparison of assays in twelve clinical laboratories in Northern Europe. European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. 38(10), s. 1933–1945. doi: 10.1007/s10096-019-03631-x. Fulltekst i vitenarkiv Vis sammendrag

  Lyme borreliosis (LB), caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex, is the most common tick-borne infection in Europe. Laboratory diagnosis of LB is mainly based on the patients' medical history, clinical signs and symptoms in combination with detection of Borrelia-specific antibodies where indirect enzyme-linked-immunosorbent assay (ELISA) is the most widely used technique. The objective of the study was to evaluate and compare the diagnostic accuracy (sensitivities and specificities) of serological tests that are currently in use for diagnosis of LB in clinical laboratories in Northern Europe, by use of a large serum panel. The panel consisted of 195 serum samples from well-characterized and classified patients under investigation for clinically suspected LB (n = 59) including patients with Lyme neuroborreliosis, Lyme arthritis, acrodermatitis chronica atrophicans, erythema migrans or other diseases (n = 112). A total of 201 serum samples from healthy blood donors were also included. The panel (396 serum samples altogether) was sent to 12 clinical laboratories (using five different ELISA methods) as blinded for group affiliation and the laboratories were asked to perform serological analysis according to their routine procedure. The results from the study demonstrated high diagnostic concordance between the laboratories using the same diagnostic assay and lower diagnostic concordance between laboratories using different diagnostic assays. For IgG, the results were in general rather homogenous and showed an average sensitivity of 88% (range 85-91%) compared to IgM which showed lower average sensitivity of 59% (range 50-67%) and more heterogeneous results between assays and laboratories.

• Lager, Malin; Faller, Maximilian; Wilhelmsson, Peter; Kjelland, Vivian; Andreassen, Åshild Kristine & Dargis, Rimtas [Vis alle 16 forfattere av denne artikkelen] (2017). Molecular detection of Borrelia burgdorferi sensu lato - An analytical comparison of real-time PCR protocols from five different Scandinavian laboratories. PLOS ONE. 12:e0185434(9), s. 1–17. doi: 10.1371/journal.pone.0185434. Fulltekst i vitenarkiv
• Strindhall, Jan; Ernerudh, Jan; Mörner, Andreas; Waalen, Kristian; Löfgren, Sture & Matussek, Andreas [Vis alle 7 forfattere av denne artikkelen] (2016). Humoral response to influenza vaccination in relation to pre-vaccination antibody titres, vaccination history, cytomegalovirus serostatus and CD4/CD8 ratio. Infectious Diseases. ISSN 2374-4235. 48(6), s. 436–442. doi: 10.3109/23744235.2015.1135252. Fulltekst i vitenarkiv
• Glasner, Corinna; Pluister, Gerlinde N.; Westh, Henrik; Arends, Jan P.A.; Empel, Joanna & Edwards, Giles F. [Vis alle 17 forfattere av denne artikkelen] (2015). Staphylococcus aureus spa type t437: Identification of the most dominant community-associated clone from Asia across Europe. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 21(2), s. 163.e1–163.e8. doi: 10.1016/j.cmi.2014.09.010. Fulltekst i vitenarkiv
• Henningsson, Anna J.; Hvidsten, Dag; Kristiansen, Bjørn Erik; Matussek, Andreas; Stuen, Snorre & Jenkins, Andrew (2015). Detection of Anaplasma phagocytophilum in Ixodes ricinus ticks from Norway using a realtime PCR assay targeting the Anaplasma citrate synthase gene gltA. BMC Microbiology. 15:153. doi: 10.1186/s12866-015-0486-5. Fulltekst i vitenarkiv Vis sammendrag

  Background: A TaqMan real-time PCR assay targeting the Anaplasma citrate synthase gene, gltA, was developed and used for detection of Anaplasma phagocytophilum in 765 Ixodes ricinus ticks collected from dogs and cats in northern Norway (n = 669) and Telemark county in southern Norway (n = 96). Results: Among the ticks from northern Norway the prevalence of A. phagocytophilum was 3.0 %, while the prevalence in southern Norway was 2.1 % (p = 0.63). The gltA PCR assay showed a high analytical sensitivity (30 genomic units) and efficiency (98.5 %), and its utility in clinical diagnostics should be evaluated in future studies. Conclusion: This is the first report of A. phagocytophilum occurrence in ticks collected north of the Arctic Circle in Norway. The prevalence is comparable to that found in Telemark county in southern Norway.

• Gustafsson, Mika; Gawel, Danuta R.; Alfredsson, Lars; Baranzini, Sergio; Bjørkander, Janne & Blomgran, Robert [Vis alle 29 forfattere av denne artikkelen] (2015). A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases. Science Translational Medicine. ISSN 1946-6234. 7:313ra178(313). doi: 10.1126/scitranslmed.aad2722. Fulltekst i vitenarkiv
• Hvidsten, Dag; Stordal, Frode; Lager, Malin; Rognerud, Bjørg; Kristiansen, Bjørn Erik & Matussek, Andreas [Vis alle 8 forfattere av denne artikkelen] (2015). Borrelia burgdorferi sensu lato-infected Ixodes ricinus collected from vegetation near the Arctic Circle. Ticks and Tick-borne Diseases. ISSN 1877-959X. 6(6), s. 768–773. doi: 10.1016/j.ttbdis.2015.07.002. Fulltekst i vitenarkiv Vis sammendrag

  This is the first study to determine the density of questing Ixodes ricinus in northern Norway. It was performed at two sites in Brønnøy, which has been known for its tick permissive habitats for decades and is one of the northernmost habitats with an abundant I. ricinus population in the world. From April to November 2011, all stages of host-seeking I. ricinus were collected from the two sites. The overall prevalence of nymphs infected with Borrelia burgdorferi sensu lato was 21% and that of adultticks 46%. The rates of the genospecies Borrelia afzelii, Borrelia garinii, and Borrelia valaisiana were similar to findings in most other studies in Scandinavia, with B. afzelii by far the most prevalent at 76%. The high Borrelia-infection prevalence in ticks from Brønnøy may explain the high incidence rate of reported Lyme borreliosis in the municipality.

• Hvidsten, Dag; Stuen, Snorre; Jenkins, Andrew; Dienus, Olaf; Olsen, Renate Slind & Kristiansen, Bjørn-Erik [Vis alle 8 forfattere av denne artikkelen] (2014). Ixodes ricinus and Borrelia prevalence at the Arctic Circle in Norway. Ticks and Tick-borne Diseases. ISSN 1877-959X. 5(2), s. 107–112. doi: 10.1016/j.ttbdis.2013.09.003. Fulltekst i vitenarkiv Vis sammendrag

  The distribution limit of Ixodes ricinus ticks in northwestern Europe (Brønnøy, Norway, 1◦ south of the Arctic Circle), has been known since the 1930s. To reconfirm this finding and extend studies in the areas adjacent to the Arctic Circle (66◦33 N), ticks were collected from dogs and cats in 8 districts in northern Norway from 64◦56 N to 68◦48 N. We detected 549 I. ricinus, 244 (44%) of them in Brønnøy district, and 305 (range 6–87 ticks) in 7 districts in the northern part of the study area. The prevalence of Borrelia in these ticks was determined by real-time PCR. In the Brønnøy district (65◦28 N, 12◦12 E), 29% of the I. ricinus were Borrelia spp.-positive, and the species B. afzelii was nearly twice as prevalent as B. garinii and/or B. valaisiana. In the study area north of Brønnøy district, only 12 (4%) of the collected ticks contained Borrelia spp. In conclusion, tick occurrence and Borrelia prevalence are high in the Brønnøy district. In contrast, I. ricinus occurrence and Borrelia prevalence are low further north across the Arctic Circle in Norway.

• Granquist, Erik Georg; Kristiansson, Malin; Lindgren, Per-Eric; Matussek, Andreas; Nødtvedt, Ane & Okstad, Wenche [Vis alle 7 forfattere av denne artikkelen] (2014). Evaluation of microbial communities and symbionts in Ixodes ricinus and ungulate hosts (Cervus elaphus and Ovis aries) from shared habitats on the west coast of Norway. Ticks and Tick-borne Diseases. ISSN 1877-959X. 5(6), s. 780–784. doi: 10.1016/j.ttbdis.2014.05.005. Fulltekst i vitenarkiv
• Lindblom, Pontus; Wilhelmsson, Peter; Fryland, Linda; Sjöwall, Johanna; Haglund, Mats & Matussek, Andreas [Vis alle 12 forfattere av denne artikkelen] (2014). Tick-borne encephalitis virus in ticks detached from humans and follow-up of serological and clinical response. Ticks and Tick-borne Diseases. ISSN 1877-959X. 5(1), s. 21–28. doi: 10.1016/j.ttbdis.2013.07.009. Fulltekst i vitenarkiv
• Jenkins, Andrew; Hvidsten, Dag; Matussek, Andreas; Lindgren, Per-Eric; Stuen, Snorre & Kristiansen, Bjørn-Erik (2012). Borrelia burgdorferi sensu lato in Ixodes ricinus ticks from Norway: evaluation of a PCR test targeting the chromosomal flaB gene. Experimental & applied acarology. ISSN 0168-8162. 58(4), s. 431–439. doi: 10.1007/s10493-012-9585-2. Fulltekst i vitenarkiv Vis sammendrag

  A consensus TaqMan real-time PCR test targeting the chromosomal flaB gene of Borrelia burgdorferi sensu lato was constructed. The test was compared with a recently published generic Light Upon eXtension (LUX) 16S rRNA real-time PCR test (Wilhelmsson et al. in J Clin Microbiol 48:4169–4176, 2010) on material consisting of 242 Ixodes ricinus ticks collected from dogs and cats in Northern Norway (n = 139) and Telemark County in Southern Norway (n = 103). Ticks positive in either test were further tested by nested PCR amplification of the 5S-23S rRNA intergenic-spacer region followed by sequencing for species identification. A tick was defined as Borrelia positive if two of three tests were positive. Thirty-four of the 242 (14 %) ticks satisfied this definition of positivity. Of these ticks 32 were positive both in the rRNA and flaB test, while two were positive only in the rRNA test. One tick was positive only in the rRNA test and was considered false positive since PCR for sequencing failed. The sensitivity of the flaB test was 94 % and the specificity 100 %. It was possible to determine the species present using Tm analysis. Among ticks from Northern Norway the prevalence of Borrelia was 13 %, whereas the prevalence in Telemark was 16 %. Among identified species (n = 33) B. afzelii was found in 16 (47 %), B. garinii in 15 (44 %) and B. valaisiana in 2 (6 %) ticks, respectively. The flaB test is a rapid, sensitive and specific test for detection and quantification of Borrelia burgdorferi s.l. in I. ricinus ticks. This is the first report on Borrelia prevalence in I. ricinus in Northern Norway.

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• Stuen, Snorre; Eskeland, Sveinung; Munderloh, Ulrike G; Barbet, Anthony F.; Lindgren, Per-Eric & Tollefsen, Stig [Vis alle 12 forfattere av denne artikkelen] (2016). A combined tissue culture and reverse vaccinology approach to develop a vaccine against Anaplasma phagocytophilum in sheep. Fulltekst i vitenarkiv
• Granquist, Erik Georg; Lindgren, Per-Eric; Matussek, Andreas; Kristiansson, Malin; Okstad, Wenche & Stuen, Snorre (2013). Biomanipulasjon og endosymbiose - En fremtidig løsning på flåttplagene? Fulltekst i vitenarkiv
• Granquist, Erik Georg; Lindgren, Per-Eric; Matussek, Andreas; Kristiansson, Malin; Okstad, Wenche & Stuen, Snorre (2013). Endosymbionts and the way forward. Fulltekst i vitenarkiv
• Granquist, Erik Georg; Lindgren, Per-Eric; Matussek, Andreas; Kristiansson, Malin; Okstad, Wenche & Stuen, Snorre (2013). Biomanipulasjon og endosymbiose - En fremtidig løsning på flåttplagene? I Brodin, Janne Karin (Red.), Husdyrforsøksmøtet 2013. Universitetet for miljø- og biovitenskap. ISSN 9788274790254. s. 297–301. Fulltekst i vitenarkiv
• Granquist, Erik Georg; Lindgren, Per-Eric; Matussek, Andreas; Kristiansson, Malin; Okstad, Wenche & Stuen, Snorre (2013). Endosymbionts in ticks of Norway - A possible target of biological manipulation and disease control? Fulltekst i vitenarkiv

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