| 1. |
- Appelberg, Sofia, et al.
(författare)
-
Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells
- 2020
-
Ingår i: Emerging Microbes & Infections. - : Informa UK Limited. - 2222-1751. ; 9:1, s. 1748-1760
-
Tidskriftsartikel (refereegranskat)abstract
- How severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections engage cellular host pathways and innate immunity in infected cells remains largely elusive. We performed an integrative proteo-transcriptomics analysis in SARS-CoV-2 infected Huh7 cells to map the cellular response to the invading virus over time. We identified four pathways, ErbB, HIF-1, mTOR and TNF signaling, among others that were markedly modulated during the course of the SARS-CoV-2 infection in vitro. Western blot validation of the downstream effector molecules of these pathways revealed a dose-dependent activation of Akt, mTOR, S6K1 and 4E-BP1 at 24 hours post infection (hpi). However, we found a significant inhibition of HIF-1α through 24hpi and 48hpi of the infection, suggesting a crosstalk between the SARS-CoV-2 and the Akt/mTOR/HIF-1 signaling pathways. Inhibition of the mTOR signaling pathway using Akt inhibitor MK-2206 showed a significant reduction in virus production. Further investigations are required to better understand the molecular sequelae in order to guide potential therapy in the management of severe coronavirus disease 2019 (COVID-19) patients.
|
|
| 2. |
- Chen, Jian, et al.
(författare)
-
Zika virus infects renal proximal tubular epithelial cells with prolonged persistency and cytopathic effects
- 2017
-
Ingår i: Emerging Microbes & Infections. - : NATURE PUBLISHING GROUP. - 2222-1751. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Zika virus (ZIKV) infection can cause fetal developmental abnormalities and Guillain-Barre syndrome in adults. Although progress has been made in understanding the link between ZIKV infection and microcephaly, the pathology of ZIKV, particularly the viral reservoirs in human, remains poorly understood. Several studies have shown that compared to serum samples, patients' urine samples often have a longer duration of ZIKV persistency and higher viral load. This finding suggests that an independent viral reservoir may exist in the human urinary system. Despite the clinical observations, the host cells of ZIKV in the human urinary system are poorly characterized. In this study, we demonstrate that ZIKV can infect renal proximal tubular epithelial cells (RPTEpiCs) in immunodeficient mice in vivo and in both immortalized and primary human renal proximal tubular epithelial cells (hRPTEpiCs) in vitro. Importantly, ZIKV infection in mouse kidneys caused caspase-3-mediated apoptosis of renal cells. Similarly, in vitro infection of immortalized and primary hRPTEpiCs resulted in notable cytopathic effects. Consistent with the clinical observations, we found that ZIKV infection can persist with prolonged duration in hRPTEpiCs. RNA-Seq analyses of infected hRPTEpiCs revealed a large number of transcriptional changes in response to ZIKV infection, including type I interferon signaling genes and anti-viral response genes. Our results suggest that hRPTEpiCs are a potential reservoir of ZIKV in the human urinary system, providing a possible explanation for the prolonged persistency of ZIKV in patients' urine.
|
|
| 3. |
|
|
| 4. |
- Hua, Y., et al.
(författare)
-
Molecular characteristics of eae-positive clinical Shiga toxin-producing Escherichia coli in Sweden
- 2020
-
Ingår i: Emerging microbes & infections. - : Informa UK Limited. - 2222-1751. ; 9:1, s. 2562-2570
-
Tidskriftsartikel (refereegranskat)abstract
- 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 (epsilon 1, gamma 1, beta 3, theta, zeta and rho) were identified eae and its subtype gamma 1 were significantly overrepresented in O157:H7 strains isolated from BD and HUS patients. epsilon 1 was associated with O121:H19 and O103:H2 strains, and beta 3 to O26:H11 strains. The combination of eae subtype gamma 1 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.
|
|
| 5. |
|
|
| 6. |
- Jensen, Jørgen Skov, et al.
(författare)
-
In vitro activity of the first-in-class triazaacenaphthylene gepotidacin alone and in combination with doxycycline against drug-resistant and -susceptible Mycoplasma genitalium
- 2020
-
Ingår i: Emerging Microbes & Infections. - : Taylor & Francis. - 2222-1751. ; 9:1, s. 1388-1392
-
Tidskriftsartikel (refereegranskat)abstract
- Mycoplasma genitalium has developed resistance to first-line azithromycin and second-line moxifloxacin. Third-line pristinamycin is only 75% effective. Gepotidacin, a novel triazaacenaphthylene topoisomerase II inhibitor, blocks bacterial DNA replication. We determined thein vitroactivity of gepotidacin alone and in combination with doxycycline against a diverse collection of Mycoplasma genitalium isolates (n = 54).Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined by a Vero-cell culture method. Macrolide resistance was present in 31 (57%) isolates, fluoroquinolone resistance in 18 (33%) isolates, and 17 (31%) had dual resistance. Synergy testing was performed for gepotidacin and doxycycline by checkerboard analysis for two macrolide- and two dual-resistant isolates.Gepotidacin was active against all 54 M. genitalium isolates with median and modal MICs of 0.125 mg/L and MIC(90)of 0.25 mg/L (range <= 0.016-0.5 mg/L). No difference in gepotidacin MIC between macrolide-resistant and -susceptible isolates (p = 0.24) or between fluoroquinolone-, dual-resistant and -susceptible isolates (p = 0.2) was demonstrated. Gepotidacin MBCs were available for 44 M. genitalium isolates with median MIC of 0.064 mg/L and median MBC of 0.125 mg/L. All isolates had <= 4-fold difference between MIC and MBC, suggesting bactericidal effect for gepotidacin. Checkerboard analysis indicated synergistic effect for gepotidacin in combination with doxycycline [fractional inhibitory concentration index (sigma FICI) of 0.5] for two isolates and additive/indifference (sigma FICI at 0.62 and 0.75) for two isolates.Gepotidacin warrants further evaluation in clinical treatment trials for M. genitalium. Combination therapy with doxycycline should be clinically studied to assess effect and potential protection against development and/or spread of gepotidacin resistance.
|
|
| 7. |
|
|
| 8. |
- Lamy, Anaïs, et al.
(författare)
-
ATP2, The essential P4-ATPase of malaria parasites, catalyzes lipid-stimulated ATP hydrolysis in complex with a Cdc50 β-subunit
- 2021
-
Ingår i: Emerging Microbes & Infections. - : Taylor & Francis. - 2222-1751. ; 10:1, s. 132-147
-
Tidskriftsartikel (refereegranskat)abstract
- Gene targeting approaches have demonstrated the essential role for the malaria parasite of membrane transport proteins involved in lipid transport and in the maintenance of membrane lipid asymmetry, representing emerging oportunites for therapeutical intervention. This is the case of ATP2, a Plasmodium-encoded 4 P-type ATPase (P4-ATPase or lipid flippase), whose activity is completely irreplaceable during the asexual stages of the parasite. Moreover, a recent chemogenomic study has situated ATP2 as the possible target of two antimalarial drug candidates. In eukaryotes, P4-ATPases assure the asymmetric phospholipid distribution in membranes by translocating phospholipids from the outer to the inner leaflet. In this work, we have used a recombinantly-produced P. chabaudi ATP2 (PcATP2), to gain insights into the function and structural organization of this essential transporter. Our work demonstrates that PcATP2 associates with two of the three Plasmodium-encoded Cdc50 proteins: PcCdc50B and PcCdc50A. Purified PcATP2/PcCdc50B complex displays ATPase activity in the presence of either phosphatidylserine or phosphatidylethanolamine. In addition, this activity is upregulated by phosphatidylinositol 4-phosphate. Overall, our work describes the first biochemical characterization of a Plasmodium lipid flippase, a first step towards the understanding of the essential physiological role of this transporter and towards its validation as a potential antimalarial drug target.
|
|
| 9. |
- Ling, Jiaxin, et al.
(författare)
-
Identification of hepatitis C virus in the common bed bug - a potential, but uncommon route for HCV infection?
- 2020
-
Ingår i: Emerging Microbes & Infections. - : TAYLOR & FRANCIS LTD. - 2222-1751. ; 9:1, s. 1429-1431
-
Tidskriftsartikel (refereegranskat)abstract
- During an ongoing virome metagenomics project we identified hepatitis C virus (HCV) in a pool of recently blood-fed common bed bug (Cimex lectularius) nymphs sampled from domestic residences in Europe. Additional PCR and genomic analysis revealed that the virus was a member of HCV genotype 3A, one of the most prevalent genotypes in Europe. Although the role of the common bed bug in the transmission of human hepatitis viruses remains unclear, our study suggests that it merits additional investigation.
|
|
| 10. |
- Magnusson, Cecilia, 1971-, et al.
(författare)
-
Characterization of a Clostridioides difficile outbreak caused by PCR ribotype 046, associated with increased mortality
- 2022
-
Ingår i: Emerging Microbes & Infections. - : Taylor & Francis. - 2222-1751. ; 11:1, s. 850-859
-
Tidskriftsartikel (refereegranskat)abstract
- This study describe a large nosocomial outbreak of Clostridioides difficile infections (CDI) dominated by ribotype (RT) 046 in a Swedish hospital. The aim of the present study was 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. In order to control the outbreak, a number of measures were successfully implemented.
|
|
