scholarly journals Posttranslational Regulation of Botulinum Neurotoxin Production in Clostridium botulinum Hall A- hyper

mSphere ◽  
2021 ◽  
Author(s):  
Heather N’te Inzalaco ◽  
William H. Tepp ◽  
Chase Fredrick ◽  
Marite Bradshaw ◽  
Eric A. Johnson ◽  
...  
Keyword(s):  
Public Health ◽  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Biologically Active ◽  
Regulatory Mechanisms ◽  
Posttranslational Regulation ◽  
Content Type

Botulinum neurotoxin (BoNT) is a public health and bioterrorism concern as well as an important and widely used pharmaceutical, yet the regulation of its synthesis by BoNT-producing clostridia is not well understood. This paper highlights the role of environmentally controlled posttranslational regulatory mechanisms influencing processing and stability of biologically active BoNTs produced by C. botulinum .

scholarly journals Closed Genome Sequence of Clostridium botulinum Strain CFSAN064329 (62A)

2018 ◽  
Vol 6 (26) ◽  
Author(s):  
Travis G. Wentz ◽  
Kuan Yao ◽  
Kristin M. Schill ◽  
N. Rukma Reddy ◽  
Guy E. Skinner ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Food Challenge ◽  
Strictly Anaerobic ◽  
Botulinum Neurotoxin A ◽  
Gram Positive ◽  
Content Type

Clostridium botulinum is a strictly anaerobic, Gram-positive, spore-forming bacterium that produces botulinum neurotoxin, a potent and deadly proteinaceous exotoxin. Clostridium botulinum strain CFSAN064329 (62A) produces an A1 serotype/subtype botulinum neurotoxin and is frequently utilized in food challenge and detection studies.

scholarly journals Alternative Sigma Factor SigK Has a Role in Stress Tolerance of Group I Clostridium botulinum Strain ATCC 3502

2013 ◽  
Vol 79 (12) ◽  
pp. 3867-3869 ◽  
Author(s):  
Elias Dahlsten ◽  
David Kirk ◽  
Miia Lindström ◽  
Hannu Korkeala
Keyword(s):  
Stress Tolerance ◽  
Sigma Factor ◽  
Clostridium Botulinum ◽  
Alternative Sigma Factor ◽  
Strain Atcc ◽  
Content Type ◽  
Osmotic Stress Tolerance ◽  
Group I ◽  
Temperature Downshift

ABSTRACTThe role of the alternative sigma factor SigK in cold and osmotic stress tolerance ofClostridium botulinumATCC 3502 was demonstrated by induction ofsigKafter temperature downshift and exposure to hyperosmotic conditions and by impaired growth of thesigKmutants under the respective conditions.

Not your typical “historian”

2018 ◽  
Vol 27 (5) ◽  
pp. 523-533
Author(s):  
Adrienne Lefevre ◽  
Madison Walter-Garcia ◽  
Kimberly Hanson ◽  
Julia Smith-Easley
Keyword(s):  
Public Health ◽  
Lessons Learned ◽  
Incident Management ◽  
Public Health Response ◽  
Content Type ◽  
Incident Command ◽  
Health Community ◽  
Health Response ◽  
Decision Making Processes

Purpose In the incident command system (ICS) structure, response documentation is formally found within the planning section. However, longer term emergency responses have demonstrated the need for a flexible and innovative role that encompasses a variety of activities, including response documentation, communications science, real-time evaluation of major themes, and information management. The paper aims to discuss this issue. Design/methodology/approach This need can be universally met through the functional role of “Historian,” a term specific to ICS, or in the case of public health response, incident management system (IMS). It should be noted that the Historian role discussed is not related to the academic study of history, but to archiving key successes and challenges during a response. Ideally the Historian should be activated at the start of an emergency response and remain active to capture the overall picture of the response, including internal information, such as lessons learned, response activities, and decision-making processes. Findings The Historian compiles details of response activities that inform leadership, donors and external communications products while alleviating pressures on the planning section. The primary, minimum output of an IMS Historian is a response timeline, which notes major internal and external events during a response with emphasis on major themes, lessons learned, and creating a user-friendly interface to display this information (see the list “Abbreviated Example of Hurricane Matthew Response Timeline” in the text). Originality/value In a world with competing priorities and ongoing emergencies, the Historian’s role of archiving details of response efforts can help the international public health community to share lessons learned and contribute to lower morbidity and mortality among those affected by emergencies.

Health reform seeks broad improvements in Chile

2019 ◽  
Keyword(s):  
Public Health ◽  
Health Reform ◽  
Content Type ◽  
The Public ◽  
Public Health Systems ◽  
Sick People ◽  
Large Numbers ◽  
Private And Public ◽  
Improve Access

Subject Health reform in Chile. Significance On April 22, President Sebastian Pinera announced two initiatives to reform Chile’s private and public health systems. The first would end years of discrimination and spiralling costs for affiliates of private health insurers, known as ISAPREs. The second aims to improve access and coverage for users of the national health service by strengthening the role of FONASA, the institution which finances the public health system. Impacts Greater competition may deepen the controversial concern that ISAPREs “cannot afford to incorporate sick people”. Fiscal revenues will fall if affiliates leave FONASA in large numbers, as expected. The delay for new ISAPRE members to access all benefits has been called discriminatory and will be a focus of debate in Congress.

scholarly journals Clostridium botulinum Strains Producing BoNT/F4 or BoNT/F5

2014 ◽  
Vol 80 (10) ◽  
pp. 3250-3257 ◽  
Author(s):  
Brian H. Raphael ◽  
Marite Bradshaw ◽  
Suzanne R. Kalb ◽  
Lavin A. Joseph ◽  
Carolina Lúquez ◽  
...  
Keyword(s):  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Southern Hybridization ◽  
Pcr Analysis ◽  
Specific Marker ◽  
Peptide Substrates ◽  
Content Type ◽  
Mass Spectral ◽  
Culture Supernatants ◽  
Specific Peptide

ABSTRACTBotulinum neurotoxin type F (BoNT/F) may be produced byClostridium botulinumalone or in combination with another toxin type such as BoNT/A or BoNT/B. Type F neurotoxin gene sequences have been further classified into seven toxin subtypes. Recently, the genome sequence of one strain ofC. botulinum(Af84) was shown to contain three neurotoxin genes (bont/F4,bont/F5, andbont/A2). In this study, eight strains containingbont/F4and seven strains containingbont/F5were examined. Culture supernatants produced by these strains were incubated with BoNT/F-specific peptide substrates. Cleavage products of these peptides were subjected to mass spectral analysis, allowing detection of the BoNT/F subtypes present in the culture supernatants. PCR analysis demonstrated that a plasmid-specific marker (PL-6) was observed only among strains containingbont/F5. Among these strains, Southern hybridization revealed the presence of an approximately 242-kb plasmid harboringbont/F5. Genome sequencing of four of these strains revealed that the genomic backgrounds of strains harboring eitherbont/F4orbont/F5are diverse. None of the strains analyzed in this study were shown to produce BoNT/F4 and BoNT/F5 simultaneously, suggesting that strain Af84 is unusual. Finally, these data support a role for the mobility of abont/F5-carrying plasmid among strains of diverse genomic backgrounds.

scholarly journals Immunoprecipitation of Native Botulinum Neurotoxin Complexes from Clostridium botulinum Subtype A Strains

2014 ◽  
Vol 81 (2) ◽  
pp. 481-491 ◽  
Author(s):  
Guangyun Lin ◽  
William H. Tepp ◽  
Marite Bradshaw ◽  
Chase M. Fredrick ◽  
Eric A. Johnson
Keyword(s):  
Gastrointestinal Tract ◽  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Protein Complexes ◽  
Host Strain ◽  
Mouse Serum ◽  
Content Type ◽  
Strain Nctc ◽  
Botulinum Neurotoxins ◽  
Subtype A

ABSTRACTBotulinum neurotoxins (BoNTs) naturally exist as components of protein complexes containing nontoxic proteins. The nontoxic proteins impart stability of BoNTs in the gastrointestinal tract and during purification and handling. The two primary neurotoxin complexes (TCs) are (i) TC1, consisting of BoNT, nontoxin-nonhemagglutinin (NTNH), and hemagglutinins (HAs), and (ii) TC2, consisting of BoNT and NTNH (and possibly OrfX proteins). In this study, BoNT/A subtypes A1, A2, A3, and A5 were examined for the compositions of their TCs in culture extracts using immunoprecipitation (IP). IP analyses showed that BoNT/A1 and BoNT/A5 form TC1s, while BoNT/A2 and BoNT/A3 form TC2s. AClostridium botulinumhost strain expressing recombinant BoNT/A4 (normally present as a TC2) from an extrachromosomal plasmid formed a TC1 with complexing proteins from the host strain, indicating that the HAs and NTNH encoded on the chromosome associated with the plasmid-encoded BoNT/A4. Strain NCTC 2916 (A1/silent B1), which carries both anhasilentbont/bcluster and anorfX bont/a1cluster, was also examined. IP analysis revealed that NCTC 2916 formed only a TC2 containing BoNT/A1 and its associated NTNH. No association between BoNT/A1 and the nontoxic proteins from the silentbont/bcluster was detected, although the HAs were expressed as determined by Western blotting analysis. Additionally, NTNH and HAs from the silentbont/bcluster did not form a complex in NCTC 2916. The stabilities of the two types of TC differed at various pHs and with addition of KCl and NaCl. TC1 complexes were more stable than TC2 complexes. Mouse serum stabilized TC2, while TC1 was unaffected.

scholarly journals Holotoxin Activity of Botulinum Neurotoxin Subtype A4 Originating from a Nontoxigenic Clostridium botulinum Expression System

2014 ◽  
Vol 80 (23) ◽  
pp. 7415-7422 ◽  
Author(s):  
Marite Bradshaw ◽  
William H. Tepp ◽  
Regina C. M. Whitemarsh ◽  
Sabine Pellett ◽  
Eric A. Johnson
Keyword(s):  
Clostridium Botulinum ◽  
Botulinum Neurotoxin ◽  
Expression System ◽  
Single Amino Acid ◽  
Content Type ◽  
Expression Host ◽  
Toxin Complex ◽  
Human Neuronal Cells

ABSTRACTClostridium botulinumsubtype A4 neurotoxin (BoNT/A4) is naturally expressed in the dual-toxin-producingC. botulinumstrain 657Ba at 100× lower titers than BoNT/B. In this study, we describe purification of recombinant BoNT/A4 (rBoNT/A4) expressed in a nonsporulating and nontoxigenicC. botulinumexpression host strain. The rBoNT/A4 copurified with nontoxic toxin complex components provided intransby the expression host and was proteolytically cleaved to the active dichain form. Activity of the recombinant BoNT/A4 in mice and in human neuronal cells was about 1,000-fold lower than that of BoNT/A1, and the recombinant BoNT/A4 was effectively neutralized by botulism heptavalent antitoxin. A previous report using recombinant truncated BoNT/A4 light chain (LC) expressed inEscherichia colihas indicated reduced stability and activity of BoNT/A4 LC compared to BoNT/A1 LC, which was surmounted by introduction of a single-amino-acid substitution, I264R. In order to determine whether this mutation would also affect the holotoxin activity of BoNT/A4, a recombinant full-length BoNT/A4 carrying this mutation as well as a second mutation predicted to increase solubility (L260F) was produced in the clostridial expression system. Comparative analyses of thein vitro, cellular, andin vivoactivities of rBoNT/A4 and rBoNT/A4-L260F I264R showed 1,000-fold-lower activity than BoNT/A1 in both the mutated and nonmutated BoNT/A4. This indicates that these mutations do not alter the activity of BoNT/A4 holotoxin. In summary, a recombinant BoNT from a dual-toxin-producing strain was expressed and purified in an endogenous clostridial expression system, allowing analysis of this toxin.

scholarly journals Public health leadership in the times of COVID-19: a comparative case study of three countries

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Jeffrey Glenn ◽  
Claire Chaumont ◽  
Pablo Villalobos Dintrans
Keyword(s):  
Public Health ◽  
Crisis Management ◽  
Active Role ◽  
The United States ◽  
Content Type ◽  
Public Leadership ◽  
The Core ◽  
Public Leaders ◽  
The Way

PurposeThe purpose is to understand the role of public leadership during the COVID-19 pandemic and advocate for a more active role of public health professionals in helping manage the crisis.Design/methodology/approachThe authors use the framework developed by Boin et al. (2005) on crisis leadership. The authors focus on three of the core tasks – sense-making, decision-making and meaning-making – that are relevant to explain the role of public leaders during the ongoing crisis. The authors draw from the experience of three countries – Chile, France and the United States – to illustrate how these tasks were exercised with concrete examples.FindingsSeveral examples of the way in which public leaders reacted to the crisis are found in the selected countries. Countries show different responses to the way they assessed and reacted to the COVID-19 as a crisis, the decisions taken to prevent infections and mitigate consequences, and the way they communicate information to the population.Practical implicationsA better understanding public leadership as a key for better crisis management, particularly for designing policy responses to public health crises. Public health leaders need to assume a more active role in the crisis management process, which also implies the emergence of a new class of public health leaders and a more prominent role for public health in the public eye.Originality/valueThe use of examples from three different countries, as well as the focus on the core leadership tasks during an ongoing crisis help not only assessing the crisis management but also extracting lessons for the coming months, as well as future public health emergencies. The three authors have a first-hand experience on the evolution of the crisis in their countries and the environment, since they are currently living and working in public health in Chile, France and the United States.

Decreasing work-related movement during a pandemic. Location analytics and the implications of the digital divide

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Joseph Taylor ◽  
Rickey Taylor
Keyword(s):  
Public Health ◽  
Digital Divide ◽  
Economic Activities ◽  
Content Type ◽  
Work Related ◽  
Movement Data ◽  
Digital Infrastructure ◽  
Positive Externalities ◽  
Travel Restrictions

Purpose The purpose of this study is to examine the role of digital infrastructure in supporting compliance with travel restrictions. The purpose of this study is to examine the role of digital infrastructure in supporting compliance with travel restrictions. In response to the COVID-19 pandemic, countries around the world have issued “stay-at-home” orders and curtailed a variety of economic activities. As countries have adopted aggressive policies to limit the spread of COVID-19, varying levels of national infrastructure to provide internet access have limited some nations’ ability to reduce travel requirements. As national policies struggle to address public health issues, location analytics enabled by big data provide unique insights regarding the efficacy of digital infrastructure. These insights can provide valuable tools to public health officials and regulators in understanding how health recommendations are implemented within an economy. Design/methodology/approach This study analyzes mobile phone movement data during the first half of 2020 and finds that countries that provided greater access to internet capabilities were better able to reduce work-related mobility. Findings This study’s findings indicate that greater levels of digital infrastructure may better prepare countries to adapt to societal disruptions such as COVID-19. Practical implications This study’s findings demonstrate that public health controls regarding movement and person-to-person interaction are less likely to be effective in nations with weaker digital infrastructure, even after accounting for variation attributable to gross domestic product (GDP) and pandemic severity. This could limit public health options in developing countries when faced with future socially disruptive events and encourage national investment in digital infrastructure. Social implications This study’s findings highlight positive externalities associated with reducing the digital divide. Developing better digital business infrastructure globally may reduce human exposure to future pandemic risks. Originality/value This research demonstrates the practical development implications of analysis of aggregate data widely available through mobile technology. As institutions develop techniques to ethically and effectively analyze this data, greater opportunities to support economic development may be revealed.

Schooling health: the critical contribution of curriculum in the 1980s

2017 ◽  
Vol 46 (2) ◽  
pp. 224-235 ◽  
Author(s):  
Deana Leahy ◽  
Dawn Penney ◽  
Rosie Welch
Keyword(s):  
Public Health ◽  
Health Education ◽  
School Health ◽  
Education Curriculum ◽  
Content Type ◽  
School Health Education ◽  
Official Curriculum ◽  
Public Health Authorities ◽  
Historical Accounts

Purpose Public health authorities have long regarded schools as important sites for improving children and young people’s health. In Australia, and elsewhere, lessons on health have been an integral component of public health’s strategy mix. Historical accounts of schools’ involvement in public health lack discussion of the role of health education curriculum. The purpose of this paper is to redress this silence and illustrate the ways health education functioned as a key governmental apparatus in Victoria in the 1980s. Design/methodology/approach The paper draws on governmentality studies to consider the explicit governmental role of official health education curriculum in the 1980s in Victoria, Australia. The authors conduct a discourse analysis of the three official curriculum texts that were released during this period to consider the main governmental rationalities and techniques that were assembled together by curriculum writers. Findings School health education functions as a key governmental apparatus of governmentality. One of its major functions is to provide opportunities to responsibilise young people with an aim to ensure that that they can perform their duty to be well. The authors demonstrate the central role of policy events in the 1970s and how they contributed to conditions of possibility that shaped versions of health education throughout the 1980s and beyond. Despite challenges posed by the critical turn in health education in the late 1980s, the governmental forces that shape health education are strong and have remained difficult to displace. Originality/value Many public health and schooling histories fail to take into account insights from the history of education and curriculum studies. The authors argue that in order to grasp the complexities of school health education, we need to consider insights afforded by curriculum histories. Historical insights can provide us with an understanding of the changing approaches to governing health in schools.

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