| 3171. |
- Ozanic, Mateja, et al.
(författare)
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Phenotypic characterization of the Francisella tularensis Delta pdpC and Delta iglG mutants
- 2016
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Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 18:12, s. 768-776
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Tidskriftsartikel (refereegranskat)abstract
- Several bacterial pathogens interact with their host through protein secretion effectuated by a type VI secretion system (T6SS). Francisella tularensis is a highly pathogenic intracellular bacterium that causes the disease tularemia. Proteins encoded by the Francisella pathogenicity island (FPI), which constitute a type VI secretion system, are essential for the virulence of the bacterium and a key mechanism behind this is the escape from the phagosome followed by productive cytosolic replication. It has been shown that T6SS in Francisella is distinct since all putative substrates of F. tularensis T6SS, except for VgrG, are unique to the species. Many of the FPI proteins are secreted into the macrophage cytosol and this is dependent on the functional components of DotU, VgrG, IglC and IglG. In addition, PdpC seems to have a regulatory role for the expression of iglABCD. Since previous results showed peculiar phenotypes of the Delta pdpC and Delta iglG mutants in mouse macrophages, their unique behavior was characterized in human monocyte-derived macrophages (HMDM) in this study. Our results show that both Delta pdpC and Delta iglG mutants of the live vaccine strain (LVS) of F. tularensis did not replicate within HMDMs. The Delta pdpC mutant did not escape from the Francisella containing phagosome (FCP), neither caused cytopathogenicity in primary macrophages and was attenuated in a mouse model. Interestingly, the Delta iglG mutant escaped from the HMDMs FCP and also caused pathological changes in the spleen and liver tissues of intradermally infected C57BL/6 mice. The Delta iglG mutant, with its unique phenotype, is a potential vaccine candidate.
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| 3172. |
- Rascovan, Nicolas, et al.
(författare)
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Emergence and Spread of Basal Lineages of Yersinia pestis during the Neolithic Decline
- 2019
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 176:1, s. 295-305
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Tidskriftsartikel (refereegranskat)abstract
- Between 5,000 and 6,000 years ago, many Neolithic societies declined throughout western Eurasia due to a combination of factors that are still largely debated. Here, we report the discovery and genome reconstruction of Yersinia pestis, the etiological agent of plague, in Neolithic farmers in Sweden, pre-dating and basal to all modern and ancient known strains of this pathogen. We investigated the history of this strain by combining phylogenetic and molecular clock analyses of the bacterial genome, detailed archaeological information, and genomic analyses from infected individuals and hundreds of ancient human samples across Eurasia. These analyses revealed that multiple and independent lineages of Y. pestis branched and expanded across Eurasia during the Neolithic decline, spreading most likely through early trade networks rather than massive human migrations. Our results are consistent with the existence of a prehistoric plague pandemic that likely contributed to the decay of Neolithic populations in Europe.
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| 3173. |
- Rukavishnikov, Grigory, et al.
(författare)
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Antimicrobial activity of antidepressants on normal gut microbiota : Results of the in vitro study
- 2023
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media S.A.. - 1662-5153. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Currently, there is little published data on the effects of antidepressants on normal gut microbiota and the consequences of such effects on treatment outcomes. The aim of the study: was to evaluate the growth kinetics of normal human gut microorganisms with antidepressants most common in routine clinical practice. Materials and methods: Research objects were species of microorganisms representing normal gut microbiota: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Candida albicans ATCC 24433, Bifidobacterium 791, Enterococcus faecalis ATCC 29212, Lactobacillus rhamnosus ATCC 53103. All microorganisms were cultivated in Schaedler broth (HiMedia) under aerobic/anaerobic conditions. The active substances of all studied antidepressants (fluvoxamine, fluoxetine, escitalopram, duloxetine, venlafaxine, mirtazapine) were extracted from ground preparations by dimethyl sulfoxide and centrifuged. Each solution of antidepressants was added to a Schaedler broth containing a certain microorganism's strain and diluted to final concentrations-200 μg/ml, 500 μg/ml, and 700 μg/ml. For a quantitative assessment of the effect, the specific growth rates (μ, h-1) of microorganisms were calculated as the slope of the initial part of the growth curve in coordinates (lnA, t). To evaluate the antidepressant effects on representatives of the normal microbiota in vitro, the following parameters were chosen: specific growth rate and IC50. Results: All antidepressants had an inhibitory effect on the growth of all studied microorganisms. Fluvoxamine and venlafaxine had the least effect on the growth activity of all studied microorganisms. Fluoxetine showed a pronounced effect on growth activity against E. coli, E. feacalis, S. aureus, and the least effect against C. albicans. Escitalopram had a greater effect on the growth rate of E. coli, E. feacalis, B. bifidum, L. rhamnosus, and C. albicans, which puts it among the leaders in terms of its effect on the growth activity of the microorganisms we studied. Mirtazapine, according to the results of our experiment, showed the greatest activity against L. rhamnosus and C. albicans. Conclusions: Our results confirm the effects of antidepressants on the growth activity of the normal gut microbiota individual strains. Further study of the antimicrobial activity of antidepressants may become one of the new directions for optimizing the personalized therapy of patients with depression.
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| 3174. |
- Smith, D. B., et al.
(författare)
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Update: proposed reference sequences for subtypes of hepatitis E virus (species Orthohepevirus A)
- 2020
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 101:7, s. 692-698
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Tidskriftsartikel (refereegranskat)abstract
- In this recommendation, we update our 2016 table of reference sequences of subtypes of hepatitis E virus (HEV; species Orthohepevirus A, family Hepeviridae) for which complete genome sequences are available (Smith et al., 2016). This takes into account subsequent publications describing novel viruses and additional proposals for subtype names; there are now eight genotypes and 36 subtypes. Although it remains difficult to define strict criteria for distinguishing between virus subtypes, and is not within the remit of the International Committee on Taxonomy of Viruses (ICTV), the use of agreed reference sequences will bring clarity and stability to researchers, epidemiologists and clinicians working with HEV.
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| 3175. |
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| 3176. |
- Stålhammar-Carlemalm, Margaretha, et al.
(författare)
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Nonimmunodominant regions are effective as building blocks in a streptococcal fusion protein vaccine.
- 2007
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1934-6069 .- 1931-3128. ; 2:6, s. 427-434
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Tidskriftsartikel (refereegranskat)abstract
- Identification of antigens that elicit protective immunity is essential for effective vaccine development. We investigated the related surface proteins of group B Streptococcus, Rib and alpha, as potential vaccine candidates. Paradoxically, nonimmunodominant regions proved to be of particular interest as vaccine components. Mouse antibodies elicited by Rib and alpha were directed almost exclusively against the C-terminal repeats and not against the N-terminal regions. However, a fusion protein derived from the nonimmunodominant N-terminal regions of Rib and alpha was much more immunogenic than one derived from the repeats and was immunogenic even without adjuvant. Moreover, antibodies to the N-terminal fusion protein protected against infection and inhibited bacterial invasion of epithelial cells. Similarly, the N-terminal region of Streptococcus pyogenes M22 protein, which is targeted by opsonic antibodies, is nonimmunodominant. These data indicate that nonimmunodominant regions of bacterial antigens could be valuable for vaccine development.
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| 3177. |
- Toh, Eric, et al.
(författare)
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Sublytic activity of a pore-forming protein from commensal bacteria causes epigenetic modulation of tumor-affiliated protein expression
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Cytolysin A (ClyA) is a pore-forming protein expressed at sublytic levels by a strongly silenced gene in non-pathogenic Escherichia coli, including typical commensal isolates in the intestinal microbiome of healthy mammalian hosts. Upon overproduction, the ClyA-expressing bacteria display a cytolytic phenotype. However, it remains unclear whether sublytic amounts of native ClyA play a role in commensal E. coli-host interactions in vivo. Here, we show that sublytic amounts of ClyA are released via outer membrane vesicles (OMVs) and can affect host cells in a profound and remarkable manner. OMVs isolated from ClyA+ E. coli were rapidly internalised into cultured colon cancer cells. The OMV-associated ClyA inhibited the expression of cancer-activating proteins such as H3K27me3, CXCR4, STAT3, and MDM2 via the EZH2/H3K27me3/miR622/CXCR4 signalling axis. Our results demonstrate that sublytic amounts of ClyA in OMVs from non-pathogenic E. coli can target the stability of the EZH2 protein to modulate epigenetics of colon cancer cells
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| 3178. |
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| 3179. |
- Vieira, Brenda, et al.
(författare)
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Role of the polyamine transporter PotABCD during biofilm formation by Streptococcus pneumoniae
- 2024
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Ingår i: PLoS ONE. - 1932-6203. ; 19:8
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae is a bacterium of great global importance, responsible for more than one million deaths per year. This bacterium is commonly acquired in the first years of life and colonizes the upper respiratory tract asymptomatically by forming biofilms that persist for extended times in the nasopharynx. However, under conditions that alter the bacterial environment, such as viral infections, pneumococci can escape from the biofilm and invade other niches, causing local and systemic disease of varying severity. The polyamine transporter PotABCD is required for optimal survival of the organism in the host. Immunization of mice with recombinant PotD can reduce subsequent bacterial colonization. PotD has also been suggested to be involved in pneumococcal biofilm development. Therefore, in this study we aimed to elucidate the role of PotABCD and polyamines in pneumococcal biofilm formation. First, the formation of biofilms was evaluated in the presence of exogenous polyamines-the substrate transported by PotABCD-added to culture medium. Next, a potABCD-negative strain was used to determine biofilm formation in different model systems using diverse levels of complexity from abiotic surface to cell substrate to in vivo animal models and was compared with its wild-type strain. The results showed that adding more polyamines to the medium stimulated biofilm formation, suggesting a direct correlation between polyamines and biofilm formation. Also, deletion of potABCD operon impaired biofilm formation in all models tested. Interestingly, more differences between wild-type and mutant strains were observed in the more complex model, which emphasizes the significance of employing more physiological models in studying biofilm formation.
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| 3180. |
- Vödrös, Dalma, et al.
(författare)
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Coreceptor usage of sequential isolates from cynomolgus monkeys experimentally infected with simian immunodeficiency virus (SIVsm)
- 2001
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Ingår i: Virology. - : Elsevier BV. - 1096-0341 .- 0042-6822. ; 291:1, s. 12-21
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Tidskriftsartikel (refereegranskat)abstract
- Sequential isolates from eight cynomolgus monkeys experimentally infected with Simian immunodeficiency virus (SIVsm, of sooty mangabey origin) were tested for coreceptor use in the human osteosarcoma indicator cell line, GHOST(3), expressing CD4 and one or another of the chemokine receptors CCR3, CCR5, CXCR4, BOB, or the orphan receptor Bonzo. The indicator cell line carries the human immunodeficiency virus type 2 long terminal repeat-driven green fluorescence protein gene that becomes activated upon infection with HIV or SIV and fluorescence can be quantitated by flow cytometric analysis. The methodological details are described in the accompanying paper (Vodros et al., 2001, Virology 290, in press). All SIVsm inoculum viruses and reisolates used CCR5 with a high level of efficiency. CCR5 use was stable over time, BOB and Bonzo use was less efficient than CCR5 use and, in particular, late isolates obtained at the time of immunodeficiency varied greatly in their coreceptor use and often could not establish a productive infection in BOB- or Bonzo-expressing cells. Unexpectedly, early reisolates obtained 12 days postinfection could infect the entire GHOST(3) panel including the parental cells. In one case this was due to use of CXCR4, either transfected or endogenously expressed on the GHOST(3) cells. Our results demonstrate the complex coreceptor use of SIVsm isolates. Moreover, they focus attention on the initial phase of virus replication when the availability of target cells may govern the replication pattern of the virus.
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