| 1. |
- Agerhäll, Martin, et al.
(author)
-
High prevalence of pharyngeal bacterial pathogens among healthy adolescents and young adults
- 2021
-
In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : John Wiley & Sons. - 0903-4641 .- 1600-0463. ; 129:12, s. 711-716
-
Journal article (peer-reviewed)abstract
- The pharyngeal mucosa can be colonized with bacteria that have potential to cause pharyngotonsillitis. By the use of culturing techniques and PCR, we aimed to assess the prevalence of bacterial pharyngeal pathogens among healthy adolescents and young adults. We performed a cross-sectional study in a community-based cohort of 217 healthy individuals between 16 and 25 years of age. Samples were analyzed for Group A streptococci (GAS), Group C/G streptococci (SDSE), Fusobacterium necrophorum, and Arcanobacterium haemolyticum. Compared to culturing, the PCR method resulted in more frequent detection, albeit in most cases with low levels of DNA, of GAS (20/217 vs. 5/217; p < 0.01) and F. necrophorum (20/217 vs. 8/217; p < 0.01). Culturing and PCR yielded similar rates of SDSE detection (14/217 vs. 12/217; p = 0.73). Arcanobacterium haemolyticum was rarely detected (3/217), and only by PCR. Overall, in 25.3% (55/217) of these healthy adolescents and young adults at least one of these pathogens was detected, a rate that is higher than previously described. Further studies are needed before clinical adoption of PCR-based detection methods for pharyngeal bacterial pathogens, as our findings suggest a high incidence of asymptomatic carriage among adolescents and young adults without throat infections.
|
|
| 2. |
|
|
| 3. |
- Boiko, Iryna, et al.
(author)
-
Genomic epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates from Ukraine, 2013-2018
- 2020
-
In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 128:7, s. 465-475
-
Journal article (peer-reviewed)abstract
- Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major health threat compromising the gonorrhoea treatment globally. AMR surveillance including whole genome sequencing (WGS)-based epidemiology provides ideal resolution to identify and describe AMR gonococcal clones, AMR determinants and populations, which can inform management guidelines and antimicrobial stewardship policies. Our aims were to, for the first time, elucidate the WGS-based epidemiology and characterise AMR determinants of gonococcal strains spreading in Ukraine, 2013-2018. Gonococcal isolates (n=150) from Ternopil and Dnipro, Ukraine (2013-2018) were subjected to AMR testing (Etest) for eight antimicrobials and WGS. Overall, 11.3% of isolates were resistant to ciprofloxacin, 6.0% to tetracycline and 0.7% to benzylpenicillin. No isolates were resistant to azithromycin, spectinomycin, ceftriaxone, or cefixime, but one isolate was bordering resistance to both cephalosporins. Twenty-five MLST STs, 50 NG-MAST STs, and 34 NG-STAR types were identified. The phylogenomic analysis revealed six main clusters, mostly associated with the internationally described multidrug-susceptible gonococcal lineage. Resistance to ciprofloxacin was associated with GyrA S91F and ParC S87R mutations; tetracyclines with rpsJ V57M and tetM; penicillins with mosaic penA-34.001 and β-lactamase; mtrR; PorB1b G101D, and PBP1 L421P mutations. One isolate of the multidrug-resistant NG-MAST ST1407, MLST ST1901 was found, which was bordering resistance to ceftriaxone and cefixime. The susceptibility of gonococcal strains spreading in Ternopil and Dnipro, Ukraine, 2013-2018 was surprisingly high. Continued and expanded gonococcal AMR surveillance, ideally including WGS, in Ukraine is essential. This could inform action plans and public health policies to control the spread of AMR gonococcal strains in Ukraine.
|
|
| 4. |
|
|
| 5. |
- Bruun-Sørensen, Anne Sofie, et al.
(author)
-
Aquaporins in pancreatic ductal adenocarcinoma
- 2021
-
In: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; 129:12, s. 700-705
-
Research review (peer-reviewed)abstract
- Aquaporins are water channel proteins facilitating passive transport of water across cellular membranes. Aquaporins are over- or ectopically expressed in a multitude of cancers, including pancreatic ductal adenocarcinoma, which is a highly aggressive cancer with low survival rate. Evidence suggests that aquaporins can affect multiple cellular processes involved in cancer development and progression including epithelial-mesenchymal transition, cellular migration, cell proliferation, invasion, and cellular adhesions. In pancreatic ductal adenocarcinoma, aquaporin-1, aquaporin-3, and aquaporin-5 are overexpressed and have been associated with metastatic processes and poor survival. Thus, aquaporin expression has been suggested as diagnostic markers and therapeutic targets in pancreatic ductal adenocarcinoma.
|
|
| 6. |
- Bystrup, Malte, et al.
(author)
-
Aquaporin-5 in breast cancer
- 2022
-
In: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; 130:5, s. 253-260
-
Research review (peer-reviewed)abstract
- The water channel aquaporin-5 (AQP5) is essential in transepithelial water transport in secretory glands. AQP5 is ectopically overexpressed in breast cancer, where expression is associated with lymph node metastasis and poor prognosis. Besides the role in water transport, AQP5 has been found to play a role in cancer metastasis, migration, and proliferation. AQP5 has also been shown to be involved in the dysregulation of epithelial cell–cell adhesion; frequently observed in cancers. Insight into the underlying molecular mechanisms of how AQP5 contributes to cancer development and progression is essential for potentially implementing AQP5 as a prognostic biomarker and to develop targeted intervention strategies for the treatment of breast cancer patients.
|
|
| 7. |
- Enkirch, Theresa, et al.
(author)
-
Molecular epidemiology of community- and hospital-associated Clostridioides difficile infections in Jönköping, Sweden, October 2017-March 2018
- 2022
-
In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 130:11, s. 661-670
-
Journal article (peer-reviewed)abstract
- Clostridioides difficile infections (CDIs) in Sweden are mostly hospital-associated (HA) with limited knowledge regarding community-associated (CA) infections. Here, we investigated the molecular epidemiology of clinical isolates of CA-CDI and HA-CDI in a Swedish county. Data and isolates (n = 156) of CDI patients (n = 122) from Jonkoping county, October 2017-March 2018, were collected and classified as CA (without previous hospital care or onset <= 2 days after admission or >12 weeks after discharge from hospital) or HA (onset >3 days after hospital admission or within 4 weeks after discharge). Molecular characterization of isolates included PCR ribotyping (n = 156 isolates) and whole genome sequencing with single nucleotide polymorphisms (SNP) analysis (n = 53 isolates). We classified 47 patients (39%) as CA-CDI and 75 (61%) as HA-CDI. Between CA-CDI and HA-CDI patients, we observed no statistically significant differences regarding gender, age, 30-day mortality or recurrence. Ribotype 005 (RR 3.1; 95% CI: 1.79-5.24) and 020 (RR 2.5; 95% CI: 1.31-4.63) were significantly associated with CA-CDI. SNP analysis identified seven clusters (0-2 SNP difference) involving 17/53 isolates of both CA-CDI and HA-CDI. Molecular epidemiology differed between CA-CDI and HA-CDI and WGS analysis suggests transmission of CDI within and between hospitals and communities.
|
|
| 8. |
|
|
| 9. |
- Foerster, Sunniva, et al.
(author)
-
The first wide-scale drug repurposing screen using the Prestwick Chemical Library (1200 bioactive molecules) against Neisseria gonorrhoeae identifies high in vitro activity of auranofin and many additional drugs
- 2020
-
In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell Publishing Inc.. - 0903-4641 .- 1600-0463. ; 128:3, s. 242-250
-
Journal article (peer-reviewed)abstract
- Treatment options for gonorrhoea are scarce. Drug repurposing of bioactive molecules approved for other conditions might therefore be of value. We developed a method for wide-scale, systematic drug repurposing screen to identify molecules with activity against Neisseria gonorrhoeae and screened the Prestwick Chemical Library (1200 FDA-approved drugs). As a proof-of-concept, we further examined one promising and interesting screening hit (auranofin; antirheumatic agent). Three WHO gonococcal reference strains (WHO F, O, P) were used for the Library screening. The strains were grown in presence of a fixed concentration of the library drugs in 384-well plates for 12 hours and the remaining bacterial respiration, to reflect growth, was then quantitatively measured using optical density (OD) 450 nm and a resazurin assay. The activity of auranofin was further examined using in vitro susceptibility testing (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)) against genetically diverse antimicrobial-resistant N. gonorrhoeae strains and time-kill assays. Sixty-eight molecules significantly inhibited bacterial growth of WHO F, O and, P. Auranofin showed potent in vitro bactericidal activity (in MIC-, MBC-, and time-kill assays) against four WHO reference strains. No cross resistance between auranofin and any antimicrobial currently or previously used for gonorrhoea treatment was found when examining 51 selected antimicrobial-resistant gonococcal strains. In conclusion, this is the first wide-scale systematic screening effort for repurposing drugs for future treatment of gonorrhoea. Additional studies examining mechanism(s) of action, resistance development, in vivo anti-gonococcal activity, and pharmacokinetics/pharmacodynamics for gonococcal infections of auranofin and several other significant screening hits would be valuable.
|
|
| 10. |
- Hadad, Ronza, 1984-, et al.
(author)
-
A Chlamydia trachomatis 23S rRNA G1523A variant escaping detection in the Aptima Combo 2 assay (Hologic) was widespread across Denmark in July-September 2019
- 2020
-
In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell Publishing Inc.. - 0903-4641 .- 1600-0463. ; 128:6, s. 440-444
-
Journal article (peer-reviewed)abstract
- Chlamydia trachomatis infection is the most common bacterial sexually transmitted infection globally, and nucleic acid amplification tests (NAATs) are recommended for highly sensitive and specific diagnosis. In early 2019, the Finnish new variant of Chlamydia trachomatis (FI-nvCT) was identified. The FI-nvCT has a C1515T mutation in the 23S rRNA gene, making it escaping detection in the Aptima Combo 2 (AC2; Hologic) NAAT, and the FI-nvCT has been subsequently reported in Sweden and Norway. In the present study, we investigated the presence of the FI-nvCT and other AC2 diagnostic-escape CT mutants in July-September 2019 in Denmark. The FI-nvCT was present but rare in Denmark. However, another AC2 diagnostic-escape CT mutant (with a 23S rRNA G1523A mutation) was found to be widespread across Denmark, accounting for 95% (76/80) of AC2 diagnostic-escape nvCT samples from five Danish CT-diagnostic laboratories. This nvCT-G1523A has previously only been detected in one single sample in the United Kingdom and Norway, respectively. It is vital to monitor the continued stability of the NAAT targets in local, national and international settings and monitor as well as appropriately analyse incidence, unexplained shifts in diagnostics rates, and/or annual collections of samples diagnosed as negative/equivocal using NAATs with different target(s). Furthermore, diagnostic CT NAATs with dual target sequences are crucial and fortunately, an updated Hologic AC2 assay including one additional target sequence is in advanced development.
|
|
