scholarly journals Genetic and Molecular Basis of Kingella kingae Encapsulation

2016 ◽  
Vol 84 (6) ◽  
pp. 1775-1784 ◽  
Author(s):  
Kimberly F. Starr ◽  
Eric A. Porsch ◽  
Patrick C. Seed ◽  
Joseph W. St. Geme
Keyword(s):  
Invasive Disease ◽  
Effective Vaccine ◽  
Structural Homology ◽  
Genetic Determinants ◽  
Kingella Kingae ◽  
Content Type ◽  
Capsule Production ◽  
Vaccine Antigens ◽  
Surface Localization

Kingella kingaeis a common cause of invasive disease in young children and was recently found to produce a polysaccharide capsule containingN-acetylgalactosamine (GalNAc) and β-3-deoxy-d-manno-octulosonic acid (βKdo). Given the role of capsules as important virulence factors and effective vaccine antigens, we set out to determine the genetic determinants ofK. kingaeencapsulation. Using a transposon library and a screen for nonencapsulated mutants, we identified the previously identifiedctrABCD(ABC transporter) operon, alipA(kpsC)-like gene, alipB(kpsS)-like gene, and a putative glycosyltransferase gene designatedcsaA(capsulesynthesis typeageneA). These genes were found to be present at unlinked locations scattered throughout the genome, an atypical genetic arrangement for Gram-negative bacteria that elaborate a capsule dependent on an ABC-type transporter for surface localization. ThecsaAgene product contains a predicted glycosyltransferase domain with structural homology to GalNAc transferases and a predicted capsule synthesis domain with structural homology to Kdo transferases, raising the possibility that this enzyme is responsible for alternately linking GalNAc to βKdo and βKdo to GalNAc. Consistent with this conclusion, mutation of the DXD motif in the GalNAc transferase domain and of the HP motif in the Kdo transferase domain resulted in a loss of encapsulation. Examination of intracellular and surface-associated capsule in deletion mutants and complemented strains further implicated thelipA(kpsC)-like gene, thelipB(kpsS)-like gene, and thecsaAgene inK. kingaecapsule production. These data define the genetic requirements for encapsulation inK. kingaeand demonstrate an atypical organization of capsule synthesis, assembly, and export genes.

scholarly journals Key Role of Capsular Polysaccharide in the Induction of Systemic Infection and Abortion by Hypervirulent Campylobacter jejuni

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Orhan Sahin ◽  
Samantha A. Terhorst ◽  
Eric R. Burrough ◽  
Zhangqi Shen ◽  
Zuowei Wu ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Campylobacter Jejuni ◽  
Capsular Polysaccharide ◽  
Systemic Infection ◽  
The United States ◽  
Content Type ◽  
Model Following ◽  
Capsule Production ◽  
Guinea Pig Model

ABSTRACT Campylobacter jejuni is a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingested Campylobacter must translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood. C. jejuni is known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a mouse model and in abortion using a pregnant guinea pig model following oral challenge. Compared with C. jejuni NCTC 11168 and 81-176, a clone SA isolate (IA3902) resulted in significantly higher bacterial counts and a significantly longer duration of bacteremia in mice. The loss of capsule production via gene-specific mutagenesis in IA3902 led to the complete abolishment of bacteremia in mice and abortion in pregnant guinea pigs, while complementation of capsule expression almost fully restored these phenotypes. The capsule mutant strain was also impaired for survival in guinea pig sera and sheep blood. Sequence-based analyses revealed that clone SA possesses a unique CPS locus with a mosaic structure, which has been stably maintained in all clone SA isolates derived from various hosts and times. These findings establish CPS as a key virulence factor for the induction of systemic infection and abortion in pregnant animals and provide a viable candidate for the development of vaccines against hypervirulent C. jejuni.

scholarly journals Kingella kingaeSurface Polysaccharides Promote Resistance to Human Serum and Virulence in a Juvenile Rat Model

2018 ◽  
Vol 86 (6) ◽  
Author(s):  
Vanessa L. Muñoz ◽  
Eric A. Porsch ◽  
Joseph W. St. Geme
Keyword(s):  
Human Serum ◽  
Invasive Disease ◽  
Complement Pathway ◽  
Kingella Kingae ◽  
Content Type ◽  
Bacterial Surface ◽  
Classical Complement Pathway ◽  
Bactericidal Effects ◽  
Pathogenic Process ◽  
Classical Complement

ABSTRACTKingella kingaeis a Gram-negative coccobacillus that is increasingly being recognized as an important cause of invasive disease in young children. The pathogenesis ofK. kingaedisease begins with colonization of the oropharynx, followed by invasion of the bloodstream, survival in the intravascular space, and dissemination to distant sites. Recent studies have revealed thatK. kingaeproduces a number of surface factors that may contribute to the pathogenic process, including a polysaccharide capsule and an exopolysaccharide. In this study, we observed thatK. kingaewas highly resistant to the bactericidal effects of human serum complement. Using mutant strains deficient in expression of capsule, exopolysaccharide, or both in assays with human serum, we found that elimination of both capsule and exopolysaccharide was required for efficient binding of IgG, IgM, C4b, and C3b to the bacterial surface and for complement-mediated killing. Abrogation of the classical complement pathway using EGTA-treated human serum restored survival to wild-type levels by the mutant lacking both capsule and exopolysaccharide, demonstrating that capsule and exopolysaccharide promote resistance to the classical complement pathway. Consistent with these results, loss of both capsule and exopolysaccharide eliminated invasive disease in juvenile rats with an intact complement system but not in rats lacking complement. Based on these observations, we conclude that the capsule and the exopolysaccharide have important redundant roles in promoting survival ofK. kingaein human serum. Each of these surface factors is sufficient by itself to fully prevent serum opsonin deposition and complement-mediated killing ofK. kingae, ultimately facilitating intravascular survival and promotingK. kingaeinvasive disease.

scholarly journals Detection of Respiratory Colonization by Kingella kingae and the Novel Kingella negevensis Species in Children: Uses and Methodology

2018 ◽  
Vol 56 (10) ◽  
Author(s):  
Pablo Yagupsky
Keyword(s):  
Invasive Disease ◽  
Nucleic Acid Amplification ◽  
The Novel ◽  
Upper Respiratory Tract ◽  
Biochemical Tests ◽  
Kingella Kingae ◽  
Content Type ◽  
Invasive Infections ◽  
Species Specific ◽  
Portal Of Entry

ABSTRACT The recognition of the role of Kingella kingae as one of the main etiologic agents of skeletal system infections in young children and the recent discovery of the novel Kingella negevensis species have resulted in an increasing interest in these two emerging pediatric pathogens. Both bacteria colonize the oropharynx and are not detected in nasopharyngeal specimens, and the colonized mucosal surface is their portal of entry to the bloodstream. Although species-specific nucleic acid amplification assays have significantly improved the detection of kingellae and facilitated patients' management, the increasing use of this diagnostic approach has the potential drawback of neglecting culture recovery of these organisms. The isolation of Kingella species enables the thorough genotyping of strains for epidemiological purposes, the study of the dynamics of asymptomatic colonization and person-to-person transmission, the investigation of the pathogenesis of invasive infections, and the determination of antibiotic susceptibility patterns. The culture isolation of pharyngeal strains and their comparison with isolates derived from normally sterile body sites may also aid in identifying virulence factors involved in the transition from colonization to invasive disease which could represent potential targets for a future protective vaccine. The two species are notoriously fastidious, and their isolation from upper respiratory tract specimens requires a short transport time, plating on selective vancomycin-containing blood-agar medium, and incubation under capnophilic and aerobic conditions. The identification of K. kingae and K. negevensis can be performed by a combination of the typical Gram stain and biochemical tests and confirmed and differentiated by molecular assays that target the groEL and mdh genes.

scholarly journals Design of Glycoconjugate Vaccines against Invasive African Salmonella enterica Serovar Typhimurium

2014 ◽  
Vol 83 (3) ◽  
pp. 996-1007 ◽  
Author(s):  
S. Rondini ◽  
F. Micoli ◽  
L. Lanzilao ◽  
M. Gavini ◽  
R. Alfini ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Invasive Disease ◽  
Careful Consideration ◽  
Effective Vaccine ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Glycoconjugate Vaccines

Nontyphoidal salmonellae, particularlySalmonella entericaserovar Typhimurium, are a major cause of invasive disease in Africa, affecting mainly young children and HIV-infected individuals. Glycoconjugate vaccines provide a safe and reliable strategy against invasive polysaccharide-encapsulated pathogens, and lipopolysaccharide (LPS) is a target of protective immune responses. With the aim of designing an effective vaccine againstS. Typhimurium, we have synthesized different glycoconjugates, by linking O-antigen and core sugars (OAg) of LPS to the nontoxic mutant of diphtheria toxin (CRM197). The OAg-CRM197conjugates varied in (i) OAg source, with threeS. Typhimurium strains used for OAg extraction, producing OAg with differences in structural specificities, (ii) OAg chain length, and (iii) OAg/CRM197ratio. All glycoconjugates were compared for immunogenicity and ability to induce serum bactericidal activity in mice.In vivoenhancement of bacterial clearance was assessed for a selectedS. Typhimurium glycoconjugate by challenge with liveSalmonella. We found that the largest anti-OAg antibody responses were elicited by (i) vaccines synthesized from OAg with the highest glucosylation levels, (ii) OAg composed of mixed- or medium-molecular-weight populations, and (iii) a lower OAg/CRM197ratio. In addition, we found that bactericidal activity can be influenced byS. Typhimurium OAg strain, most likely as a result of differences in OAg O-acetylation and glucosylation. Finally, we confirmed that mice immunized with the selected OAg-conjugate were protected againstS. Typhimurium colonization of the spleen and liver. In conclusion, our findings indicate that differences in the design of OAg-based glycoconjugate vaccines against invasive AfricanS. Typhimurium can have profound effects on immunogenicity and therefore optimal vaccine design requires careful consideration.

scholarly journals Identification of Conserved Candidate Vaccine Antigens in the Surface Proteome ofGiardia lamblia

2019 ◽  
Vol 87 (6) ◽  
Author(s):  
Barbara J. Davids ◽  
Ching M. Liu ◽  
Elaine M. Hanson ◽  
Christine H. Y. Le ◽  
Jonathan Ang ◽  
...  
Keyword(s):  
Diarrheal Disease ◽  
Surface Antigens ◽  
Surface Proteins ◽  
Secretory Iga ◽  
Intestinal Lumen ◽  
Effective Vaccine ◽  
Content Type ◽  
Veterinary Vaccine ◽  
Surface Localization ◽  
Surface Proteome

ABSTRACTGiardia lamblia, one of the most common protozoal infections of the human intestine, is an important worldwide cause of diarrheal disease, malabsorption, malnutrition, delayed cognitive development in children, and protracted postinfectious syndromes. Despite its medical importance, no human vaccine is available against giardiasis. A crude veterinary vaccine has been developed, and experimental vaccines based on expression of multiple variant-specific surface proteins have been reported, but poorly defined vaccine components and excessive antigen variability are problematic for pharmaceutical vaccine production. To expand the repertoire of antigen candidates for vaccines, we reasoned that surface proteins may provide an enriched source of such antigens since key host effectors, such as secretory IgA, can directly bind to such antigens in the intestinal lumen and interfere with epithelial attachment. Here, we have applied a proteomics approach to identify 23 novel surface antigens ofG. lambliathat show >90% amino acid sequence identity between the two human-pathogenic genetic assemblages (A and B) of the parasite. Surface localization of a representative subset of these proteins was confirmed by immunostaining. Four selected proteins, uridine phosphorylase-like protein-1, protein 21.1 (GL50803_27925), α1-giardin, and α11-giardin, were subsequently produced in recombinant form and shown to be immunogenic in mice andG. lamblia-infected humans and confer protection againstG. lambliainfection upon intranasal immunization in rodent models of giardiasis. These results demonstrate that identification of conserved surface antigens provides a powerful approach for overcoming a key rate-limiting step in the design and construction of an effective vaccine against giardiasis.

Long-term management of patients with multiple brain metastases after shaped beam radiosurgery

2004 ◽  
pp. 406-412
Author(s):  
Paul Okunieff ◽  
Michael C. Schell ◽  
Russell Ruo ◽  
E. Ronald Hale ◽  
Walter G. O'Dell ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Tumor Control ◽  
Content Type ◽  
Negative Results ◽  
Multiple Metastases ◽  
Extracranial Disease ◽  
Successful Control ◽  
The Brain

✓ The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.

scholarly journals Vulnerable adults in police custody

2019 ◽  
Vol 22 (1) ◽  
pp. 5-8
Author(s):  
Ian Cummins
Keyword(s):  
Design Methodology ◽  
Research Literature ◽  
Police Custody ◽  
England And Wales ◽  
Content Type ◽  
Increased Risk ◽  
Vulnerable Adults

Purpose The purpose of this paper is to discuss the recent National Appropriate Adult Network (NAAN) report on the role of the appropriate adult. Design/methodology/approach This paper is based on the NAAN report and a review of relevant policy and research literature. Findings There to Help 2 highlights that there are still significant gaps in the provision of appropriate adult schemes across England and Wales. These gaps potentially place vulnerable adults at increased risk. Originality/value This paper is a review of recent research.

Financial access and economic development: the moderating role of financial consumer protection

2019 ◽  
Vol 15 (4) ◽  
pp. 406-424 ◽  
Author(s):  
Maryam Kriese ◽  
Joshua Yindenaba Abor ◽  
Elikplimi Agbloyor
Keyword(s):  
Economic Development ◽  
World Bank ◽  
Financial Literacy ◽  
Compliance Monitoring ◽  
Financial Access ◽  
Policy Makers ◽  
Content Type ◽  
The World Bank ◽  
Moderating Role

Purpose The purpose of this paper is to examine the moderating role of financial consumer protection (FCP) in the access–development nexus. Design/methodology/approach The study is based on cross-country data on 102 countries surveyed in the World Bank Global Survey on FCP and Financial Literacy (2013). The White heteroscedasticity adjusted regressions and Two-stage least squares regressions (2SLS) are used for the estimation. Findings Interactions between FCP regulations that foster fair treatment, disclosure, dispute resolution and recourse and financial access have positive net effects on economic development. However, there is no sufficient evidence to suggest that interactions between financial access and enforcement and compliance monitoring regulations have a significant effect on economic development. Practical implications First, policy makers should continue with efforts aimed at instituting FCP regimes as part of strategies aimed at broadening access to financial services for enhanced economic development. Second, instituting FCP regimes per se may not be enough. Policy makers need to consider possible intervening factors such as the provision of adequate resources and supervisory authority, for compliance monitoring and enforcement to achieve the expected positive effect on economic development. Originality/value This study extends evidence in the law–finance–growth literature by providing empirical evidence on the effect of legal institution specific to the protection of retail financial consumers on the access–development nexus using a nouvel data set, the World Bank Global survey on FCP and Financial Literacy (2013).

Categorization flexibility and unconventional choices: is life an adventure?

2020 ◽  
Vol 54 (8) ◽  
pp. 1963-1986
Author(s):  
Tilottama G. Chowdhury ◽  
Feisal Murshed
Keyword(s):  
Interactive Effect ◽  
Interactive Effects ◽  
Cognitive Capacity ◽  
Purchase Behavior ◽  
Consumer Decision Making ◽  
Cross Sectional ◽  
Content Type ◽  
Cross Domain ◽  
Multiple Domains

Purpose This paper proposes that categorization flexibility, operationalized as the cognitive capacity that cross-categorizes products in multiple situational categories across multiple domains, might favorably influence a consumer’s evaluation of unconventional options. Design/methodology/approach Experimental research design is used to test the theory. An exploratory study first establishes the effect of categorization flexibility in a non-food domain. Study 1 documents the moderating role of decision domain, showing that the effect works only under low- (vs high-) consequence domain. Studies 2A and 2B further refine the notion by showing that individuals can be primed in a relatively higher categorization flexibility frame of mind. Study 3 demonstrates the interactive effect of categorization flexibility and adventure priming in a high-consequence domain. Study 4 integrates the interactive effects of decisions with low- vs high-consequence, adventure priming and categorization flexibility within a single decision domain of high consequence. Findings Consumers with higher- (vs lower-) categorization flexibility tend to opt for unconventional choices when the decision domain entails low consequences, whereas such a result does not hold under decision domain of high consequences. The categorization flexibility effects in case of low-consequence decision domain holds true even when consumers are primed to be categorization flexible. Furthermore, with additional adventure priming, consumers show an increased preference for unconventional options even under a decision domain with high consequence. Research limitations/implications This study could not examine real purchase behavior as results are based on cross-sectional, behavioral intention data. In addition, it did not examine the underlying reason for presence of cross-domain categorization flexibility index. Practical implications The results suggest that stimuli may be tailored to consumers in ways that increase the salience and the perceived attractiveness of unconventional choices. Further, data reinforce the notion of cross-categorical interrelations among different domains, which could be leveraged by marketers. Originality/value This study represents the first documentation of the potential ways by which unconventional product choice might be a function of individuals’ categorization flexibility level across different types of decision domains. The findings yield implications that are novel to both categorization and consumer decision-making literature.

The path of support-to-sales: mediating role of seller collaborative information exchange in social commerce

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Li Chen ◽  
Fengxia Zhu ◽  
Murali Mantrala
Keyword(s):  
Information Exchange ◽  
Instrumental Support ◽  
Trade Volume ◽  
Social Commerce ◽  
Content Type ◽  
Mediating Role ◽  
The Social ◽  
Source Data ◽  
Negative Effect

Purpose This paper aims to systematically investigate the direct and indirect effects of four types of support – peer instrumental support, peer emotional support, platform business support and platform communication support – on seller trade volume in social commerce. It also aims to uncover the path of support-to-sales of the seller from a platform perspective and provides a more complete picture of the social commerce phenomenon. Design/methodology/approach This paper uses multi-source data including primary survey data and secondary data on trade volume to test the hypotheses. PROCESS mediation model is used to analyze the multi-source data set. Findings This study finds that the positive effects of peer instrumental support, platform business support and platform communication support on seller trade volume are fully mediated by seller collaborative information exchange. Also, peer emotional support has a significant negative effect on seller trade volume and collaborative information exchange can serve as a buffer to mitigate the negative effect. Research limitations/implications The authors provide new insights into what types of support are or are not conducive to improving transaction volume of individual sellers and highlight the mediating role of seller information exchange in this value generation process in social commerce. These findings advance current knowledge of how seller interactions increase value in social commerce. The chosen research setting may limit the generalizability of the findings of this study. Practical implications This paper offers valuable implications for social commerce platforms on how to better serve their sellers to achieve high growth. Specifically, the findings suggest that platforms should encourage instrumental support and information exchange among peer sellers. In addition, platforms should expand seller support from a single-focus on sellers’ business to a dual-focus on both sellers’ business and socialization in social commerce. Originality/value This paper fulfills an identified need to study how sellers can better derive value from the social interactions and how social commerce platforms can effectively influence transactions, support sales and serve as a selling platform.

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