scholarly journals Influence of Shigella flexneri 2a O Antigen Acetylation on Its Bacteriophage Sf6 Receptor Activity and Bacterial Interaction with Human Cells

2020 ◽  
Vol 202 (24) ◽  
Author(s):  
Min Yan Teh ◽  
Axel Furevi ◽  
Göran Widmalm ◽  
Renato Morona
Keyword(s):  
Shigella Flexneri ◽  
Limited Range ◽  
World Health ◽  
Bacteriophage Therapy ◽  
Chemical Modifications ◽  
Content Type ◽  
O Antigen ◽  
Shigella Flexneri 2A ◽  
Bacterial Interaction ◽  
Health Organization

ABSTRACT Shigella flexneri is a major causative agent of bacillary dysentery in developing countries, where serotype 2a2 is the prevalent strain. To date, approximately 30 serotypes have been identified for S. flexneri, and the major contribution to the emergence of new serotypes is chemical modifications of the lipopolysaccharide (LPS) component O antigen (Oag). Glucosylation, O-acetylation, and phosphoethanolamine (PEtN) modifications increase the Oag diversity, providing benefits to S. flexneri. LPS Oag acts as a primary receptor for bacteriophage Sf6, which infects only a limited range of S. flexneri serotypes (Y and X). It uses its tailspike protein (Sf6TSP) to establish initial interaction with LPS Oags that it then hydrolyzes. Currently, there is a lack of comprehensive study on the parent and serotype variant strains from the same genetic background and an understanding of the importance of LPS Oag O-acetylations. Therefore, a set of isogenic strains (based on S. flexneri 2457T [2a2]) with deletions of different Oag modification genes (oacB, oacD, and gtrII) that resemble different naturally occurring serotype Y and 2a strains was created. The impacts of these Oag modifications on S. flexneri sensitivity to Sf6 and the pathogenesis-related properties were then compared. We found that Sf6TSP can hydrolyze serotype 2a LPS Oag, identified that 3/4-O-acetylation is essential for resistance of serotype 2a strains to Sf6, and showed that serotype 2a strains have better invasion ability. Lastly, we revealed two new serotype conversions for S. flexneri, thereby contributing to understanding the evolution of this important human pathogen. IMPORTANCE The emergence of antibiotic-resistant strains and lack of efficient vaccines have made Shigella a priority organism for the World Health Organization (1). Therefore, bacteriophage therapy has received increasing attention as an alternative therapeutic approach. LPS Oag is the most variable part of LPS due to chemical modifications and is the target of bacteriophage Sf6 (S. flexneri specific). We dissected the evolution of S. flexneri serotype Y to 2a2, which revealed a new role for a gene acquired during serotype conversion and furthermore identified new specific forms of LPS receptor for Sf6. Collectively, these results unfold the importance of the acquisition of those Oag modification genes and further our understanding of the relationship between Sf6 and S. flexneri.

scholarly journals Stable Chromosomal Expression of Shigella flexneri 2a and 3a O-Antigens in the Live Salmonella Oral Vaccine Vector Ty21a

2017 ◽  
Vol 24 (12) ◽  
Author(s):  
Madushini N. Dharmasena ◽  
Manuel Osorio ◽  
Kazuyo Takeda ◽  
Scott Stibitz ◽  
Dennis J. Kopecko
Keyword(s):  
Oral Vaccine ◽  
Shigella Flexneri ◽  
Serum Antibody ◽  
Vaccine Vector ◽  
Shigella Dysenteriae ◽  
Antigenic Determinants ◽  
Content Type ◽  
O Antigen ◽  
Shigella Flexneri 2A ◽  
O Antigens

ABSTRACT We have been exploring the use of the live attenuated Salmonella enterica serovar Typhi Ty21a vaccine strain as a versatile oral vaccine vector for the expression and delivery of multiple foreign antigens, including Shigella O-antigens. In this study, we separately cloned genes necessary for the biosynthesis of the Shigella flexneri serotype 2a and 3a O-antigens, which have been shown to provide broad cross-protection to multiple disease-predominant S. flexneri serotypes. The cloned S. flexneri 2a rfb operon, along with bgt and gtrII, contained on the SfII bacteriophage, was sufficient in Ty21a to express the heterologous S. flexneri 2a O-antigen containing the 3,4 antigenic determinants. Further, this rfb operon, along with gtrA, gtrB, and gtrX contained on the Sfx bacteriophage and oac contained on the Sf6 bacteriophage, was sufficient to express S. flexneri 3a O-antigen containing the 6, 7, and 8 antigenic determinants. Ty21a, with these plasmid-carried or chromosomally inserted genes, demonstrated simultaneous and stable expression of homologous S. Typhi O-antigen plus the heterologous S. flexneri O-antigen. Candidate Ty21a vaccine strains expressing heterologous S. flexneri 2a or 3a lipopolysaccharide (LPS) elicited significant serum antibody responses against both homologous S. Typhi and heterologous Shigella LPS and protected mice against virulent S. flexneri 2a or 3a challenges. These new S. flexneri 2a and 3a O-antigen-expressing Ty21a vaccine strains, together with our previously constructed Ty21a strains expressing Shigella sonnei or Shigella dysenteriae 1 O-antigens, have the potential to be used together for simultaneous protection against the predominant causes of shigellosis worldwide as well as against typhoid fever.

scholarly journals Buruli Ulcer: Review of a Neglected Skin Mycobacterial Disease

2017 ◽  
Vol 56 (4) ◽  
Author(s):  
Jeannette Guarner
Keyword(s):  
Clinical Presentation ◽  
Oral Treatment ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
World Health ◽  
Tissue Necrosis ◽  
Content Type ◽  
Skin Nodule ◽  
The World ◽  
Health Organization

ABSTRACTBuruli ulcer is caused byMycobacterium ulcerans. This neglected disease occurs in scattered foci around the world, with a higher concentration of cases in West Africa. The mycobacteria produce mycolactones that cause tissue necrosis. The disease presents as a painless skin nodule that ulcerates as necrosis expands. Finding acid-fast bacilli in smears or histopathology, culturing the mycobacteria, and performingM. ulceransPCR in presumptive cases confirm the diagnosis. Medical treatment with oral rifampin and intramuscular streptomycin or oral treatment with rifampin plus clarithromycin for 8 weeks is supported by the World Health Organization. This review summarizes the epidemiology, pathogenesis, clinical presentation, diagnostic tests, and advances in treatment.

The elderly caregiver questionnaire for COVID-19 (ECQC-24)

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Hanif Abdul Rahman ◽  
Wegdan Bani Issa ◽  
Mohammad Rababa ◽  
Deeni Rudita Idris ◽  
Khadizah H. Abdul-Mumin ◽  
...  
Keyword(s):  
Factor Analysis ◽  
Design Methodology ◽  
Reliability And Validity ◽  
The Elderly ◽  
World Health ◽  
Psychometric Analysis ◽  
Content Type ◽  
The Us ◽  
Caregiver Questionnaire ◽  
Health Organization

Purpose The purpose of this paper is to introduce a new tool called the elderly caregiver questionnaire for COVID-19 (ECQC-24) that helps to assess caregiver attributes toward best possible care for elderly during this pandemic. Design/methodology/approach ECQC-24 was developed based on international team of experts and draw upon latest advice from reliable governing bodies such as World Health Organization and the US Centre of Disease Control. Psychometric analysis was applied to ensure the newly developed ECQC-24 is valid and reliable. Findings Cronbach’s alpha ranged from 0.72 to 0.87, and construct validity by exploratory factor analysis was acceptable. The results provide good estimates for the reliability and validity of ECQC-24. Originality/value More evidence is urgently needed to better inform clinicians, health and social policymakers and related stakeholders and organizations involved in caring for the elderly. ECQC-24, the manual to use and analyzing tools are freely available for download and use at https://sites.google.com/view/the-elderly-caregiver-covid19/home.

Vaccine hesitancy and implications on childhood immunisation in Malaysia

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Noor Hazilah Abd Manaf ◽  
Mohd Azahadi Omar ◽  
Fatin Husna Suib
Keyword(s):  
World Health ◽  
Health Concern ◽  
Vaccine Hesitancy ◽  
Personal Choice ◽  
Childhood Immunisation ◽  
Content Type ◽  
Factors Affecting ◽  
Parental Decision ◽  
Islamic Medicine ◽  
Health Organization

PurposeThe World Health Organization identified vaccine hesitancy as one of the ten threats to global health in 2019. The purpose of this paper is to evaluate the implications and factors affecting parental decision on childhood immunisation in Malaysia.Design/methodology/approachThis paper reviews literature on vaccine hesitancy and evaluation of factors affecting parental decision on childhood immunisation in Malaysia.FindingsVaccine hesitancy is a growing public health concern in Malaysia with factors such as influence of Internet and social media, personal choice and individual right, conspiracy theory, religious reasons and alternative medicine as among the influencing dynamics. An urban, educated demography operating within a postmodern medical paradigm compounds the diminishing value of vaccines.Originality/valueThis paper provides a comprehensive examination of vaccine hesitancy in Malaysia. Critical appraisal on personal choice over societal responsibility within an Asian/Muslim collectivist society has not been discussed in previous studies. The acceptance of homeopathy as an Islamic medicine alternative is peculiar to multi-ethnic, multi-cultural Malaysia.

scholarly journals Final orientation for new graduates on the highest attainable standard of health

2019 ◽  
Vol 33 (5) ◽  
pp. 362-365
Author(s):  
Samlee Plianbangchang
Keyword(s):  
Self Care ◽  
Good Health ◽  
Individual Responsibility ◽  
World Health ◽  
Public Health Workforce ◽  
Content Type ◽  
New Graduates ◽  
National Medical ◽  
The Government ◽  
Health Organization

Purpose The purpose of this paper is to discuss the importance of taking responsibility for our own self-care as fundamental to achieving optimum healthcare at all levels: family, community and country. However, for self-care to work at its best, the support of the government and the national medical and public health workforce are required in addition to increased facilities that ensure the development and long-term maintenance of a person’s health status. Moreover, inter-disciplinary government policy, strategy and resource support should be placed as a central part of the national healthcare development system. Design/methodology/approach It is a commentary piece of work from own long experience in working with the World Health Organization. Findings The value of self-care and individual responsibility in achieving one’s own good health ultimately results in improved national and global health standards. Originality/value This commentary explores the ideas and concepts on ways and means of leading people to think and act toward achieving their own optimum health in order to lead a socially and economically productive life and ultimately achieve “the highest attainable standard of health,” a WHO objective.

scholarly journals The Acinetobacter baumannii Znu System Overcomes Host-Imposed Nutrient Zinc Limitation

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Laura E. Hesse ◽  
Zachery R. Lonergan ◽  
William N. Beavers ◽  
Eric P. Skaar
Keyword(s):  
Acinetobacter Baumannii ◽  
Defense Mechanisms ◽  
Pathogenic Bacteria ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
World Health ◽  
Content Type ◽  
Nutritional Immunity ◽  
Essential Nutrient ◽  
Health Organization

ABSTRACT Acinetobacter baumannii is an opportunistic bacterial pathogen capable of causing a variety of infections, including pneumonia, sepsis, wound, and burn infections. A. baumannii is an increasing threat to public health due to the prevalence of multidrug-resistant strains, leading the World Health Organization to declare A. baumannii a “Priority 1: Critical” pathogen, for which the development of novel antimicrobials is desperately needed. Zinc (Zn) is an essential nutrient that pathogenic bacteria, including A. baumannii, must acquire from their hosts in order to survive. Consequently, vertebrate hosts have defense mechanisms to sequester Zn from invading bacteria through a process known as nutritional immunity. Here, we describe a Zn uptake (Znu) system that enables A. baumannii to overcome this host-imposed Zn limitation. The Znu system consists of an inner membrane ABC transporter and an outer membrane TonB-dependent receptor. Strains of A. baumannii lacking any individual Znu component are unable to grow in Zn-starved conditions, including in the presence of the host nutritional immunity protein calprotectin. The Znu system contributes to Zn-limited growth by aiding directly in the uptake of Zn into A. baumannii cells and is important for pathogenesis in murine models of A. baumannii infection. These results demonstrate that the Znu system allows A. baumannii to subvert host nutritional immunity and acquire Zn during infection.

scholarly journals Comparison of Western Immunobloting to an Enzyme-Linked Immunosorbent Assay for the Determination of Anti-Bordetella pertussis Antibodies

2011 ◽  
Vol 18 (4) ◽  
pp. 615-620 ◽  
Author(s):  
Stephen D. Merrigan ◽  
Ryan J. Welch ◽  
Christine M. Litwin
Keyword(s):  
Immunosorbent Assay ◽  
Bordetella Pertussis ◽  
World Health ◽  
Enzyme Linked Immunosorbent Assay ◽  
Recent Infection ◽  
Content Type ◽  
Igm Elisa ◽  
Iga Antibodies ◽  
Health Organization

ABSTRACTDuringBordetella pertussisinfection, it has been established that an increase of anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibodies occurs. Immunoblots from two manufacturers using FHA and PT antigens were compared with an enzyme-linked immunosorbent assay (ELISA) that used both FHA and PT. One manufacturer used two concentrations of PT bands for the IgG immunoblot, calibrated to the World Health Organization standard for PT in international units (IU/ml), 100 IU/ml (PT-100) and 8 IU/ml (PT). The second immunoblot kit measured antibodies to a single calibrated PT band. Both kits measured IgA antibodies, and one additionally measured IgM antibodies. Two of 41 (5%) ELISA IgM positives were confirmed positive by IgM immunoblotting, suggesting poor specificity of the IgM ELISA. The agreements of the IgG and IgA immunoblots with the ELISA ranged from 72.5% to 85.3%, with only 38 to 51% of IgA positives confirmed by immunoblotting and only 61 to 68% of IgG positives confirmed by immunoblotting. The two immunoblots correlated well with each other, with 91.7% and 94.3% agreement for IgG and IgA, respectively. When the FHA band was used with the PT band as the criterion for positivity, significant differences existed in specificity compared to the ELISA (IgG, 84.1% versus 33.3%; IgA, 82.4% versus 71.0%). When the positive IgA immunoblots (evidence of natural recent infection) were compared to the positive PT-100 IgG immunoblots (evidence of recent infection or vaccination), the PT-100 blot showed a 71% sensitivity in detecting natural recent infection.B. pertussisimmunoblots, alone or in combination with ELISAs, can aid in the diagnosis ofB. pertussisinfection.

scholarly journals Aminoglycoside Heteroresistance inAcinetobacter baumanniiAB5075

mSphere ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Sarah E. Anderson ◽  
Edgar X. Sherman ◽  
David S. Weiss ◽  
Philip N. Rather
Keyword(s):  
Acinetobacter Baumannii ◽  
Population Analysis ◽  
World Health ◽  
Dependent Manner ◽  
Aminoglycoside Resistance ◽  
Gene Encoding ◽  
Integrase Gene ◽  
Content Type ◽  
Mechanistic Basis ◽  
Health Organization

ABSTRACTHeteroresistance is a phenomenon where a subpopulation of cells exhibits higher levels of antibiotic resistance than the general population. Analysis of tobramycin resistance inAcinetobacter baumanniiAB5075 using Etest strips demonstrated that colonies with increased resistance arose at high frequency within the zone of growth inhibition. The presence of a resistant subpopulation was confirmed by population analysis profiling (PAP). The tobramycin-resistant subpopulation was cross resistant to gentamicin but not amikacin. The increased tobramycin resistance phenotype was highly unstable, and cells reverted to a less resistant population at frequencies of 60 to 90% after growth on nonselective media. Furthermore, the frequency of the resistant subpopulation was not increased by preincubation with subinhibitory concentrations of tobramycin. The tobramycin-resistant subpopulation was shown to replicate during the course of antibiotic treatment, demonstrating that these were not persister cells. InA. baumanniiAB5075, a large plasmid (p1AB5075) carriesaadB, a 2″-nucleotidyltransferase that confers resistance to both tobramycin and gentamicin but not amikacin. TheaadBgene is part of an integron and is carried adjacent to four additional resistance genes that are all flanked by copies of an integrase gene. In isolates with increased resistance, this region was highly amplified in a RecA-dependent manner. However, in arecAmutant, colonies with unstable tobramycin resistance arose by a mechanism that did not involve amplification of this region. These data indicate that tobramycin heteroresistance occurs by at least two mechanisms inA. baumannii, and future studies to determine its effect on patient outcomes are warranted.IMPORTANCEAcinetobacter baumanniihas become an important pathogen in hospitals worldwide, where the incidence of these infections has been increasing.A. baumanniiinfections have become exceedingly difficult to treat due to a rapid increase in the frequency of multidrug- and pan-resistant isolates. This has prompted the World Health Organization to listA. baumanniias the top priority for the research and development of new antibiotics. This study reports for the first time a detailed analysis of aminoglycoside heteroresistance inA. baumannii. We define the mechanistic basis for heteroresistance, where theaadB(ant2″)Iagene encoding an aminoglycoside adenylyltransferase becomes highly amplified in a RecA-dependent manner. Remarkably, this amplification of 20 to 40 copies occurs stochastically in 1/200 cells in the absence of antibiotic selection. In addition, we provide evidence for a second RecA-independent mechanism for aminoglycoside heteroresistance. This study reveals that aminoglycoside resistance inA. baumanniiis far more complex than previously realized and has important implications for the use of aminoglycosides in treatingA. baumanniiinfections.

COVID-19 alters focus of cyberespionage

2020 ◽  
Keyword(s):  
Civil Society ◽  
World Health Organization ◽  
World Health ◽  
Research Institutions ◽  
Content Type ◽  
Pharmaceutical Firms ◽  
Civil Society Organisations ◽  
Multilateral Institutions ◽  
The World ◽  
Health Organization

Significance Calls by the UN and civil society organisations for a cyberspace ‘ceasefire’ have made little difference. Impacts Trust in multilateral institutions such as the World Health Organization will be undermined if they suffer cyberattacks. Post-pandemic, China is likely to experience a rise in cyber intrusions from upcoming cyber actors such as Vietnam. Although better prepared than research institutions, large pharmaceutical firms are not immune to cyberespionage.

Cerebellar liponeurocytoma

2001 ◽  
Vol 95 (4) ◽  
pp. 700-703 ◽  
Author(s):  
Thad R. Jackson ◽  
William F. Regine ◽  
Dianne Wilson ◽  
Daron G. Davis
Keyword(s):  
World Health ◽  
Treatment Modalities ◽  
Central Nervous System Neoplasms ◽  
Content Type ◽  
Biological Potential ◽  
Cerebellar Liponeurocytoma ◽  
Pertinent Information ◽  
Health Organization ◽  
Nervous System Neoplasms

✓ Cerebellar liponeurocytoma is a rare tumor of the posterior fossa that has many morphological similarities to medulloblastoma and neurocytoma. Recently the World Health Organization working group for classification of central nervous system neoplasms adopted the term “cerebellar liponeurocytoma” to provide a unified nomenclature for a tumor variously labeled in the literature as lipomatous medulloblastoma, lipidized medulloblastoma, medullocytoma, neurolipocytoma, lipomatous glioneurocytoma, and lipidized mature neuroectodermal tumor of the cerebellum. The rarity of this tumor and paucity of pertinent information regarding its biological potential and natural history have resulted in the application of various treatment modalities. It is suggested in the available literature that these lesions have a much more favorable prognosis than typical medulloblastomas, and that adjuvant therapy for liponeurocytoma need not be as extensive as that administered for medulloblastomas.

Sign in / Sign up

Export Citation Format

Share Document