| 1. |
- Anwar, Naeem
(författare)
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Oxidoreductases and RNA degradosome controlling virulence-associated traits of Salmonella enterica serovar Typhimurium
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The oxidative stress response is a fundamental and primitive mode of innate immune defense in nearly all forms of life. The host oxidative stress response becomes truly important and effective especially against intracellular pathogens such as Salmonella. Pathogens have evolved diverse mechanisms to withstand the oxidative responses. These include the use of oxidoreductases to neutralize oxidative products and repair oxidative damages, rapid alteration in their transcriptome and diversion of such oxidative products in cellular signaling, for their survival and successful infection. In the first study in this thesis, we have introduced the putative ScsABCD oxidoreductases of the thioredoxin superfamily for their role in oxidative stress tolerance and in virulence of S. Typhimurium. We demonstrated that ScsABCD proteins are dispensable for invasion in cultured epithelial cells under normal invasive conditions, although ScsABCD acts as a suppressor of SPI-1 mediated invasion upon oxidative stress. Our results have further shown a functional association between ScsABCD and thiroredoxin 1 (TrxA) oxidoreductase of S. Typhimurium. In this, we demonstrated that absence of ScsABCD restored the invasiveness of a trxA mutant in epithelial cells and its virulence in C. elegans. (Paper I). Next, we present the analyses on the role of periplasmic Dsb oxidoreductase system in S. Typhimurium’s biofilm-development, specifically under redox stress. In this, we show that DsbA and DsbB act as suppressors of rdar-morphotype development and affect biofilm-regulation using either Csg-dependent or -independent mechanism, respectively. Our results further reveal that oxidative stress abrogates rdar-morphotype of S. Typhimurium, whereas reductive stress reduces rdar-morphotype with concomitant plentiful release of extracellular slimy material containing, notably, the extracellular DNA (eDNA). Furthermore, we have demonstrated the oxidative recovery of swimming motility defects of a dsbA mutant. (Paper II). Finally, we have demonstrated that exoribonuclease; PNPase and its genetic associate membrane lipoprotein NlpI constitute an operon and are functionally connected (Papers III and IV). PNPase was required for rdar-morphotype development whereas, NlpI suppresses the biofilm formation. In addition, we established the association of PNPase with c-di-GMP metabolism in biofilm regulation. Moreover, we showed that both PNPase and NlpI are required, independently, for cold adaptation of S. Typhimurium.
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| 2. |
- Khan, H. R., et al.
(författare)
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Cross-cultural prevalence of sleep quality and psychological distress in healthcare workers during COVID-19 pandemic
- 2021
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Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279 .- 2162-3279. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Poor quality sleep and emotional disturbances are expected in times of crisis. COVID-19 has severely impacted healthcare worldwide and with that comes the concern about its effects on healthcare workers. The purpose of the present study was to assess sleep quality and psychological distress in healthcare workers during the COVID-19 pandemic.Methods: The present work is a multi-centric cross-sectional study targeting healthcare workers from India, Pakistan, and Nepal. It used an online version of the Pittsburg Sleep Quality Index and the General Health Questionnaire, and data were analyzed using SPSS V.24.Results: A total of 1790 participants completed the questionnaire. Of the 1790 participants, 57% reported poor sleep quality, and 10% reported a high level of psychological distress. A cross-cultural comparison found some differences between the different groups of participants. The details of the differences were further explored in the article.Conclusion: The present study highlights that a significant proportion of healthcare workers are affected by poor sleep quality and psychological distress during the COVID-19 pandemic. It also emphasizes the imperative to provide them with psychosocial support to avoid potential short- and long-term psychological consequences of these troubling times.
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| 3. |
- Koskiniemi, Sanna, et al.
(författare)
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Pathoadaptive Mutations in Salmonella enterica Isolated after Serial Passage in Mice
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e70147-
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Tidskriftsartikel (refereegranskat)abstract
- How pathogenic bacteria adapt and evolve in the complex and variable environment of the host remains a largely unresolved question. Here we have used whole genome sequencing of Salmonella enterica serovar Typhimurium LT2 populations serially passaged in mice to identify mutations that adapt bacteria to systemic growth in mice. We found unique pathoadaptive mutations in two global regulators, phoQ and stpA, which increase the competitive indexes of the bacteria 3- to 5-fold. Also, all mouse-adapted lineages had changed the orientation of the hin invertable element, resulting in production of a FliC type of flagellum. Competition experiments in mice with locked flagellum mutants showed that strains expressing the FliC type of flagellum had a 5-fold increase in competitive index as compared to those expressing FljB type flagellum. Combination of the flagellum cassette inversion with the stpA mutation increased competitive indexes up to 20-fold. These experiments show that Salmonella can rapidly adapt to a mouse environment by acquiring a few mutations of moderate individual effect that when combined confer substantial increases in growth.
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| 4. |
- Lofton, Hava, et al.
(författare)
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Fitness of Salmonella mutants resistant to antimicrobial peptides
- 2015
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 70:2, s. 432-440
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine the effects of mutations in the waaY, phoP and pmrB genes, which confer resistance to antimicrobial peptides (AMPs), on fitness of Salmonella Typhimurium. Methods: Survival during low pH, oxidative stress, stationary-phase incubation, exposure to serum and bile and growth in mice and laboratory media were determined by time-kills, disc inhibition assays, competition experiments and optical density measurements. Results: Individual mutations in the waaY gene (involved in LPS core biosynthesis) and in the phoP and pmrB genes (part of two different two-component regulatory systems, phoPQ and pmrAB) conferred no or minor effects on bacterial survival during stressful in vitro conditions or in mice. In contrast, a waaY-phoP-pmrB triple mutant was compromised under most assay conditions. Conclusions: Results from this study show that AMP resistance can be cost-free, as assessed by several assays that attempt to mimic the conditions a bacterium might encounter within a host. Our findings imply that future therapeutic use of AMPs could select for fit mutants with cross-resistance to human defence peptides and that potential resistance development in response to therapeutic use of AMPs needs to be carefully monitored.
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| 5. |
- Wrande, Marie, et al.
(författare)
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Replication of Salmonella enterica serovar Typhimurium in RAW264.7 Phagocytes Correlates With Hypoxia and Lack of iNOS Expression
- 2020
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Salmonella infection associates with tissue hypoxia, while inducible nitric oxide synthase (iNOS), relying for its activity on molecular oxygen, stands as a central host defence measure in murine salmonellosis. Here, we have detailed hypoxia and iNOS responses of murine macrophage-like RAW264.7 cells upon infection with Salmonella enterica serovar Typhimurium. We noted that only a proportion of the infected RAW264.7 cells became hypoxic or expressed iNOS. Heavily infected cells became hypoxic, while in parallel such cells tended not to express iNOS. While a proportion of the infected RAW264.7 cells revealed shutdown of protein synthesis, this was only detectable after 12 h post infection and after iNOS expression was induced in the cell culture. Our data implicate an intrinsic heterogeneity with regard to hypoxia and iNOS expression in a cell culture-based infection setting.
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