scholarly journals Shigella sonnei O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Jayne L. Watson ◽  
Julia Sanchez-Garrido ◽  
Philippa J. Goddard ◽  
Vincenzo Torraca ◽  
Serge Mostowy ◽  
...  
Keyword(s):  
Cell Death ◽  
Low Income ◽  
Diarrheal Disease ◽  
Shigella Flexneri ◽  
Shigella Sonnei ◽  
Low Income Countries ◽  
Inflammasome Activation ◽  
Content Type ◽  
O Antigen ◽  
Key Aspects

ABSTRACT Two Shigella species, Shigella flexneri and Shigella sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle- and high-income countries. S. flexneri is a prototypic cytosolic bacterium; once intracellular, it rapidly escapes the phagocytic vacuole and causes pyroptosis of macrophages, which is important for pathogenesis and bacterial spread. In contrast, little is known about the invasion, vacuole escape, and induction of pyroptosis during S. sonnei infection of macrophages. We demonstrate here that S. sonnei causes substantially less pyroptosis in human primary monocyte-derived macrophages and THP1 cells. This is due to reduced bacterial uptake and lower relative vacuole escape, which results in fewer cytosolic S. sonnei and hence reduced activation of caspase-1 inflammasomes. Mechanistically, the O-antigen (O-Ag), which in S. sonnei is contained in both the lipopolysaccharide and the capsule, was responsible for reduced uptake and the type 3 secretion system (T3SS) was required for vacuole escape. Our findings suggest that S. sonnei has adapted to an extracellular lifestyle by incorporating multiple layers of O-Ag onto its surface compared to other Shigella species. IMPORTANCE Diarrheal disease remains the second leading cause of death in children under five. Shigella remains a significant cause of diarrheal disease with two species, S. flexneri and S. sonnei, causing the majority of infections. S. flexneri are well known to cause cell death in macrophages, which contributes to the inflammatory nature of Shigella diarrhea. Here, we demonstrate that S. sonnei causes less cell death than S. flexneri due to a reduced number of bacteria present in the cell cytosol. We identify the O-Ag polysaccharide which, uniquely among Shigella spp., is present in two forms on the bacterial cell surface as the bacterial factor responsible. Our data indicate that S. sonnei differs from S. flexneri in key aspects of infection and that more attention should be given to characterization of S. sonnei infection.

scholarly journals Shigella sonnei O-antigen inhibits internalisation, vacuole escape and inflammasome activation

2019 ◽  
Author(s):  
Jayne L Watson ◽  
Julia Sanchez-Garrido ◽  
Philippa J Goddard ◽  
Vincenzo Torraca ◽  
Serge Mostowy ◽  
...  
Keyword(s):  
Low Income ◽  
Dominant Species ◽  
Shigella Sonnei ◽  
Surface Structures ◽  
Low Income Countries ◽  
Inflammasome Activation ◽  
O Antigen ◽  
Caspase 1 ◽  
Primary Monocyte ◽  
Bacterial Uptake

AbstractTwo Shigella species, flexneri and sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle and high-income countries. S. flexneri is a prototypic cytosolic bacterium; once intracellular it rapidly escapes the phagocytic vacuole and causes pyroptosis of macrophages, which is important for pathogenesis and bacterial spread. By contrast little is known about the invasion, vacuole escape and induction of pyroptosis during S. sonnei infection of macrophages. We demonstrate that S. sonnei causes substantially less pyroptosis in human primary monocyte-derived macrophages and THP1 cells. This is due to reduced bacterial uptake and lower relative vacuole escape, which results in fewer cytosolic S. sonnei and hence reduced activation of caspase-1 inflammasomes. Mechanistically, the O-antigen, which in S. sonnei is contained in both the lipopolysaccharide and the capsule, was responsible for reduced uptake and the T3SS was required for vacuole escape. Our findings suggest that S. sonnei has adapted to an extracellular lifestyle by incorporating additional O-antigen into its surface structures compared to other Shigella species.

scholarly journals Conformational and Immunogenicity Studies of the Shigella flexneri Serogroup 6 O-Antigen: The Effect of O-Acetylation

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 432
Author(s):  
Nicole Inge Richardson ◽  
Neil Ravenscroft ◽  
Vanessa Arato ◽  
Davide Oldrini ◽  
Francesca Micoli ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Low Income ◽  
Diarrheal Disease ◽  
Repeat Unit ◽  
Shigella Flexneri ◽  
Low Income Countries ◽  
Effective Vaccine ◽  
Antigen Delivery ◽  
O Antigen

The pathogenic bacterium Shigella is a leading cause of diarrheal disease and mortality, disproportionately affecting young children in low-income countries. The increasing prevalence of antibiotic resistance in Shigella necessitates an effective vaccine, for which the bacterial lipopolysaccharide O-antigen is the primary target. S. flexneri serotype 6 has been proposed as a multivalent vaccine component to ensure broad protection against Shigella. We have previously explored the conformations of S. flexneri O-antigens from serogroups Y, 2, 3, and 5 that share a common saccharide backbone (serotype Y). Here we consider serogroup 6, which is of particular interest because of an altered backbone repeat unit with non-stoichiometric O-acetylation, the antigenic and immunogenic importance of which have yet to be established. Our simulations show significant conformational changes in serogroup 6 relative to the serotype Y backbone. We further find that O-acetylation has little effect on conformation and hence may not be essential for the antigenicity of serotype 6. This is corroborated by an in vivo study in mice, using Generalized Modules for Membrane Antigens (GMMA) as O-antigen delivery systems, that shows that O-acetylation does not have an impact on the immune response elicited by the S. flexneri serotype 6 O-antigen.

scholarly journals Shigella sonneiDoes Not Use Amoebae as Protective Hosts

2018 ◽  
Vol 84 (9) ◽  
Author(s):  
Jayne Watson ◽  
Claire Jenkins ◽  
Abigail Clements
Keyword(s):  
Low Income ◽  
Legionella Pneumophila ◽  
Shigella Flexneri ◽  
Low Income Countries ◽  
Public Health Issue ◽  
Free Living ◽  
Middle Income ◽  
Content Type ◽  
Protective Environment ◽  
Alternative Scenarios

ABSTRACTShigella flexneriandShigella sonneibacteria cause the majority of all shigellosis cases worldwide. However, their distributions differ, withS. sonneipredominating in middle- and high-income countries andS. flexneripredominating in low-income countries. One proposed explanation for the continued range expansion ofS. sonneiis that it can survive in amoebae, which could provide a protective environment for the bacteria. In this study, we demonstrate that while bothS. sonneiandS. flexnerican survive coculture with the free-living amoebaeAcanthamoebae castellanii, bacterial growth is predominantly extracellular. All isolates ofShigellawere degraded following phagocytosis byA. castellanii, unlike those ofLegionella pneumophila, which can replicate intracellularly. Our data suggest thatS. sonneiis not able to use amoebae as a protective host to enhance environmental survival. Therefore, alternative explanations forS. sonneiemergence need to be considered.IMPORTANCEThe distribution ofShigellaspecies closely mirrors a country's socioeconomic conditions. With the transition of many populous nations from low- to middle-income countries,S. sonneiinfections have emerged as a major public health issue. Understanding whyS. sonneiinfections are resistant to improvements in living conditions is key to developing methods to reduce exposure to this pathogen. We show that free-living amoebae are not likely to be environmental hosts ofS. sonnei, as allShigellastrains tested were phagocytosed and degraded by amoebae. Therefore, alternative scenarios are required to explain the emergence and persistence ofS. sonneiinfections.

scholarly journals Molecular Modeling of the Shigella flexneri Serogroup 3 and 5 O-Antigens and Conformational Relationships for a Vaccine Containing Serotypes 2a and 3a

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 643
Author(s):  
Jason Hlozek ◽  
Sara Owen ◽  
Neil Ravenscroft ◽  
Michelle M. Kuttel
Keyword(s):  
Diarrheal Disease ◽  
Shigella Flexneri ◽  
Quadrivalent Vaccine ◽  
Slight Effect ◽  
Work Support ◽  
O Antigen ◽  
The Common ◽  
O Antigens ◽  
Chain Conformations ◽  
Shared Epitopes

The pathogenic bacterium Shigella flexneri is a leading global cause of diarrheal disease. The O-antigen is the primary vaccine target and distinguishes the 30 serotypes reported. Except for serotype 6, all S. flexneri serotypes have a common backbone repeating unit (serotype Y), with variations in substitution creating the various serotypes. A quadrivalent vaccine containing serotypes 2a and 3a (as well as 6 and Shigella sonnei) is proposed to provide broad protection against non-vaccine S. flexneri serotypes through shared epitopes and conformations. Here we model the O-antigen (O-Ag) conformations of serogroups 3 and 5: a continuation of our ongoing systematic study of the S. flexneri O-antigens that began with serogroup 2. Our simulations show that S. flexneri serogroups 2, 3, and 5 all have flexible O-Ags, with substitutions of the backbone altering the chain conformations in different ways. Our analysis suggests three general heuristics for the effects of substitution on the Shigella O-Ag conformations: (1) substitution on rhamnose C reduces the extension of the O-Ag chain; (2) substitution at O-3 of rhamnose A restricts the O-Ags to predominantly helical conformations, (3) substitution at O-3 of rhamnose B has only a slight effect on conformation. The common O-Ag conformations across serotypes identified in this work support the assumption that a quadrivalent vaccine containing serotypes 2a and 3a could provide coverage against S. flexneri serotype 3b and serogroup 5.

Foreign capital inflows and economic growth: the experience of low-income countries in Sub Saharan Africa

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Atif Awad
Keyword(s):  
Low Income ◽  
Foreign Capital ◽  
Ordinary Least Squares ◽  
Capital Inflows ◽  
Sub Saharan Africa ◽  
Low Income Countries ◽  
Content Type ◽  
Long Run ◽  
Foreign Capital Inflows ◽  
The Impact

Purpose This paper aims to investigate the long-run impact of selected foreign capital inflows, including aid, remittances, foreign direct investment (FDI), trade and debt, on the economic growth of 21 low-income countries in the Sub Saharan Africa (SSA) region, during the period 1990–2018. Design/methodology/approach To obtain this objective and for robust analysis, a parametric approach, which was dynamic ordinary least squares, and a non-parametric technique, which was fully modified ordinary least squares, were used. Findings The results of both models confirmed that, in the long run, trade and aid affected the growth rate of the per capita income in these countries in a positive way. However, external debt seemed to have an adverse influence on such growth. Originality/value First, this is the initial study that has addressed this matter across a homogenous group of countries in the SSA region. Second, while most of the previous studies regarding capital inflows into the SSA region have focused on the impact of only one or two aspects of such foreign capital inflows on growth, the present study, instead, examined the impact of five types of foreign capital inflows (aid, remittances, FDI, trade and debt).

scholarly journals Genetic Mechanisms behind the Spread of Reduced Susceptibility to Azithromycin in Shigella Strains Isolated from Men Who Have Sex with Men in Québec, Canada

2018 ◽  
Vol 63 (2) ◽  
pp. e01679-18 ◽  
Author(s):  
Khadidja Yousfi ◽  
Christiane Gaudreau ◽  
Pierre A. Pilon ◽  
Brigitte Lefebvre ◽  
Matthew Walker ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Shigella Flexneri ◽  
Complete Sequence ◽  
Shigella Sonnei ◽  
Content Type ◽  
Genetic Mechanisms ◽  
Sex With Men

ABSTRACT We analyzed 254 Shigella species isolates collected in Québec, Canada, during 2013 and 2014. Overall, 23.6% of isolates showed reduced susceptibility to azithromycin (RSA) encoded by mphA (11.6%), ermB (1.7%), or both genes (86.7%). Shigella strains with RSA were mostly isolated from men who have sex with men (68.8% or higher) from the Montreal region. A complete sequence analysis of six selected plasmids from Shigella sonnei and different serotypes of Shigella flexneri emphasized the role of IS26 in the dissemination of RSA.

Private school vouchers for expanding secondary school access? The case of Tanzania

2018 ◽  
Vol 32 (7) ◽  
pp. 1307-1318
Author(s):  
Donald R. Baum ◽  
Jacobus Cilliers
Keyword(s):  
Secondary Education ◽  
Secondary School ◽  
Low Income ◽  
Private School ◽  
Systems Approach ◽  
Financial Burden ◽  
Low Income Countries ◽  
Urban District ◽  
Content Type ◽  
School Voucher

Purpose The purpose of this paper is to provide insight into the current contributions of private schools to education provision in Tanzania, and to consider the feasibility of a school voucher program to contribute to the expansion of the secondary school system, compared to the alternative expansion of public secondary education. Design/methodology/approach The study offers an analysis of current educational circumstances and educational goals in Tanzania, and projects differential costs and outcomes associated with various options for expanding secondary education. Data come from two sources: a census of the private schooling market in the Morogoro Urban district, conducted as part of the World Bank’s Systems Approach for Better Education Results initiative; and Tanzania’s National Panel Survey 2010–2011. Findings For those students unable to cover the full cost of secondary education, findings suggest that a targeted private school voucher would be an efficient and equitable policy mechanism for secondary school expansion. Such an approach would ease the financial burden on government for constructing all new schools, yet assure access for the most vulnerable. Originality/value The implementation of school voucher programs is increasing in low-income countries. It is important for policy makers to carefully consider the appropriateness of this type of policy intervention for their particular educational contexts. This paper models an approach by which researchers and policymakers can assess the educational circumstances of a particular location, and determine the potential effectiveness of a private school voucher policy.

Cross-cultural metacognition as a prior for humanitarian knowledge: when cultures collide in global health emergencies

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Tachia Chin ◽  
Jianwei Meng ◽  
Shouyang Wang ◽  
Yi Shi ◽  
Jianxin Zhang
Keyword(s):  
Low Income ◽  
A Priori ◽  
Normative Theory ◽  
Cross Cultural ◽  
Warning Signs ◽  
Low Income Countries ◽  
Global Public Health ◽  
Business World ◽  
Content Type ◽  
Cultural Conflicts

Purpose A serious global public health emergency (GPHE) like the COVID-19 aggravates the inequilibrium of medical care and other critical resources between wealthy and poor nations, which, coupled with the collision of cultures, indicates the vital need for developing humanitarian knowledge transcending cultures. Given the scarcity of literature addressing such unprecedent issues, this paper thus proposes new, unconventional viewpoints and future themes at the intersection of knowledge management (KM) and humanitarian inquiry. Design/methodology/approach This paper is conceptual in nature. The data of the World Bank and the Office for the Coordination of Humanitarian Affairs are analysed to introduce some emerging real impact topics regarding cross-cultural conflicts and humanitarian knowledge in the post-COVID business world. The theoretical foundation was built upon a critical literature review. Findings This paper synthesizes the perspectives of culture, KM and the humanistic philosophy to distil the core component of cultural intelligence and comparatively and thereby illuminating why cross-cultural metacognition acts as a priori for achieving cosmopolitan humanitarian knowledge. Research limitations/implications This paper provides profound implications to academics by highlighting the importance to formulating new, inter-disciplinary themes or unorthodox, phenomenon-driven assumptions beyond the traditional KM domain. This paper also offers practitioners and policymakers valuable insights into coping with the growing disparity between high- and low-income countries by showing warning signs of a looming humanitarian crisis associated with a GPHE context. Originality/value This paper does not aim to claim the birth of a new domain but call for more research on developing a normative theory of humanitarian knowledge as transcendence of cultures. It implies uncharted territories of great interest and potential for the real impact KM community.

scholarly journals Global e-government development: besides the relative wealth of countries, do policies matter?

2020 ◽  
Vol 14 (3) ◽  
pp. 381-400 ◽  
Author(s):  
Gonçalo Paiva Dias
Keyword(s):  
Low Income ◽  
Public Policies ◽  
Low Income Countries ◽  
Political Commitment ◽  
Content Type ◽  
Secondary Sources ◽  
Relative Wealth ◽  
Innovative Thinking ◽  
High Level ◽  
Government Development

Purpose This study aims to investigate whether, discounting the effect of the relative wealth of countries, it is possible to observe the relevance of policies for e-government development. Design/methodology/approach The deviations of countries' results from what could be expected, considering their relative wealth is calculated by using the residuals of a linear regression using the Gross Domestic Product per capita as the independent variable and the UN E-Government Development Index as the dependent variable. The countries that achieve better and worse results than expected are then identified and their cases are analyzed by resorting to secondary sources, namely, published research referring to their cases. Those research documents were identified by successively searching the Scopus database, the Google Scholar database and the Web of Science. Findings The existence of formal e-government strategies and plans and the capacity to implement them can make a difference, allowing countries to achieve better results than expected or, in their absence, to perform worse than expected. Research limitations/implications The proposed methodology can be useful to e-government researchers, particularly as a basis for deeper and more detailed studies. Practical implications Countries should invest in well-developed and focused strategies and continuity of public policies and their capacity to deliver results. For that purpose, political commitment and high-level coordination are key factors. For low-income countries, long-lasting cooperation with external experienced partners is crucial. For high-income countries, innovative thinking is a key enabler. Originality/value This study uses an innovative method to look beyond the effect of the relative wealth of countries and investigate the relevance of public policies for e-government development.

State fragility and human development: a study with special emphasis on social cohesion

2020 ◽  
Vol 48 (1) ◽  
pp. 39-61
Author(s):  
Belay Seyoum
Keyword(s):  
Human Development ◽  
Social Cohesion ◽  
Low Income ◽  
Ordinary Least Squares ◽  
Low Income Countries ◽  
Least Squares Regression ◽  
Content Type ◽  
State Fragility ◽  
State Legitimacy ◽  
The Impact

PurposeThe purpose of this paper is to examine the effect of state fragility on select indicators of human development and identify aspects of state fragility that have the greatest impact on poverty reduction and sustainable development. The paper also explores the impact of social cohesion on human development as well as the mediating role of state legitimacy in mediating the relationship between social cohesion and human development.Design/methodology/approachThe study is based on data from 180 countries and uses ordinary least squares regression and mediation analysis to explore the effects of social cohesion on human development.FindingsThe findings show a significant relationship between state fragility and human development. It suggests that policies and efforts aimed at enhancing social cohesion would have the most significant impact on human development. The findings also show that social cohesion not only has a direct effect on human development but it also has an indirect effect on human development through state legitimacy (mediator).Practical implicationsEven though state fragility has been largely associated with low income countries, different facets of fragility are manifested in various countries regardless of levels of economic development.Originality/valueThe study is timely in view of the evidence of increasing state fragility in many countries. Furthermore, this is the first scholarly work linking lack of social cohesion, state fragility and human development.

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