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 USA300 and USA500 Clonal Lineages of Staphylococcus aureus Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the cap5 Locus

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Susan Boyle-Vavra ◽  
Xue Li ◽  
Md Tauqeer Alam ◽  
Timothy D. Read ◽  
Julia Sieth ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Capsular Polysaccharide ◽  
The United States ◽  
Whole Genome Sequence ◽  
Content Type ◽  
Capsule Production ◽  
Usa300 Strain

ABSTRACTThe surface capsular polysaccharide (CP) is a virulence factor that has been used as an antigen in several successful vaccines against bacterial pathogens. A vaccine has not yet been licensed againstStaphylococcus aureus, although two multicomponent vaccines that contain CP antigens are in clinical trials. In this study, we evaluated CP production in USA300 methicillin-resistantS. aureus(MRSA) isolates that have become the predominant community-associated MRSA clones in the United States. We found that all 167 USA300 MRSA and 50 USA300 methicillin-susceptibleS. aureus(MSSA) isolates were CP negative (CP−). Moreover, all 16 USA500 isolates, which have been postulated to be the progenitor lineage of USA300, were also CP−. Whole-genome sequence analysis of 146 CP−USA300 MRSA isolates revealed they all carry acap5locus with 4 conserved mutations compared with strain Newman. Genetic complementation experiments revealed that three of these mutations (in thecap5promoter,cap5Dnucleotide 994, andcap5Enucleotide 223) ablated CP production in USA300 and that Cap5E75 Asp, located in the coenzyme-binding domain, is essential for capsule production. All but three USA300 MSSA isolates had the same fourcap5mutations found in USA300 MRSA isolates. Most isolates with a USA500 pulsotype carried three of these four USA300-specific mutations, suggesting the fourth mutation occurred in the USA300 lineage. Phylogenetic analysis of thecaploci of our USA300 isolates as well as publicly available genomes from 41 other sequence types revealed that the USA300-specificcap5mutations arose sequentially inS. aureusin a common ancestor of USA300 and USA500 isolates.IMPORTANCEThe USA300 MRSA clone emerged as a community-associated pathogen in the United States nearly 20 years ago. Since then, it has rapidly disseminated and now causes health care-associated infections. This study shows that the CP-negative (CP−) phenotype has persisted among USA300 isolates and is a universal and characteristic trait of this highly successful MRSA lineage. It is important to note that a vaccine consisting solely of CP antigens would not likely demonstrate high efficacy in the U.S. population, where about half of MRSA isolates comprise USA300. Moreover, conversion of a USA300 strain to a CP-positive (CP+) phenotype is unlikelyin vivoorin vitrosince it would require the reversion of 3 mutations. We have also established that USA300 MSSA isolates and USA500 isolates are CP−and provide new insight into the evolution of the USA300 and USA500 lineages.

scholarly journals Critical Role of LuxS in the Virulence of Campylobacter jejuni in a Guinea Pig Model of Abortion

2011 ◽  
Vol 80 (2) ◽  
pp. 585-593 ◽  
Author(s):  
Paul Plummer ◽  
Orhan Sahin ◽  
Eric Burrough ◽  
Rachel Sippy ◽  
Kathy Mou ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Campylobacter Jejuni ◽  
Type Strain ◽  
Wild Type Strain ◽  
Critical Role ◽  
Wild Type ◽  
Direct Role ◽  
Content Type

ABSTRACTPrevious studies onCampylobacter jejunihave demonstrated the role of LuxS in motility, cytolethal distending toxin production, agglutination, and intestinal colonization; however, its direct involvement in virulence has not been reported. In this study, we demonstrate a direct role ofluxSin the virulence ofC. jejuniin two different animal hosts. The IA3902 strain, a highly virulent sheep abortion strain recently described by our laboratory, along with its isogenicluxSmutant andluxScomplement strains, was inoculated by the oral route into both a pregnant guinea pig virulence model and a chicken colonization model. In both cases, the IA3902luxSmutant demonstrated a complete loss of ability to colonize the intestinal tract. In the pregnant model, the mutant also failed to induce abortion, while the wild-type strain was highly abortifacient. Genetic complementation of theluxSgene fully restored the virulent phenotype in both models. Interestingly, when the organism was inoculated into guinea pigs by the intraperitoneal route, no difference in virulence (abortion induction) was observed between theluxSmutant and the wild-type strain, suggesting that the defect in virulence following oral inoculation is likely associated with a defect in colonization and/or translocation of the organism out of the intestine. These studies provide the first direct evidence that LuxS plays an important role in the virulence ofC. jejuniusing anin vivomodel of natural disease.

scholarly journals Spo0A Suppresses sin Locus Expression in Clostridioides difficile

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Babita Adhikari Dhungel ◽  
Revathi Govind
Keyword(s):  
Diarrheal Disease ◽  
Toxin Production ◽  
The United States ◽  
Upstream Region ◽  
Pcr Analysis ◽  
Bacterial Cells ◽  
Master Regulator ◽  
Content Type ◽  
Clostridioides Difficile

ABSTRACT Clostridioides difficile is the leading cause of nosocomial infection and is the causative agent of antibiotic-associated diarrhea. The severity of the disease is directly associated with toxin production, and spores are responsible for the transmission and persistence of the organism. Previously, we characterized sin locus regulators SinR and SinR′ (we renamed it SinI), where SinR is the regulator of toxin production and sporulation. The SinI regulator acts as its antagonist. In Bacillus subtilis, Spo0A, the master regulator of sporulation, controls SinR by regulating the expression of its antagonist, sinI. However, the role of Spo0A in the expression of sinR and sinI in C. difficile had not yet been reported. In this study, we tested spo0A mutants in three different C. difficile strains, R20291, UK1, and JIR8094, to understand the role of Spo0A in sin locus expression. Western blot analysis revealed that spo0A mutants had increased SinR levels. Quantitative reverse transcription-PCR (qRT-PCR) analysis of its expression further supported these data. By carrying out genetic and biochemical assays, we show that Spo0A can bind to the upstream region of this locus to regulates its expression. This study provides vital information that Spo0A regulates the sin locus, which controls critical pathogenic traits such as sporulation, toxin production, and motility in C. difficile. IMPORTANCE Clostridioides difficile is the leading cause of antibiotic-associated diarrheal disease in the United States. During infection, C. difficile spores germinate, and the vegetative bacterial cells produce toxins that damage host tissue. In C. difficile, the sin locus is known to regulate both sporulation and toxin production. In this study, we show that Spo0A, the master regulator of sporulation, controls sin locus expression. Results from our study suggest that Spo0A directly regulates the expression of this locus by binding to its upstream DNA region. This observation adds new detail to the gene regulatory network that connects sporulation and toxin production in this pathogen.

The future of maternity wear: Generation Z's expectations of dressing for pregnancy

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Elizabeth Anne Weigle ◽  
Laura McAndrews
Keyword(s):  
United States ◽  
Online Survey ◽  
The United States ◽  
The Body ◽  
Content Type ◽  
Longitudinal Approach ◽  
Shopping Experience ◽  
Physical Changes ◽  
Practical Implications

PurposeThe purpose of this paper is to investigate Generation Z's physical expectations of being pregnant and their outlook for maternity wear shopping.Design/methodology/approachFemales in this cohort (n = 207) participated in an online survey that included questions about perceptions of pregnancy, physical self-concept and forecasted shopping behaviors.FindingsResults indicated that this group is concerned with physical changes of pregnancy and expect to treat each area of the body in a different way. Women's expected physical concerns of pregnancy predict how much they anticipate accentuating their pregnant body. Gen Z anticipates wearing loose maternity garments and they envision a thoughtful, in-store shopping experience for styles that are equally fashionable and comfortable, such as dresses.Research limitations/implicationsThis study should be extended to future generational cohorts like Generation Alpha, along with Gen Z outside of the United States and women in the United States who are non-white. Further studies should take a longitudinal approach to gauge changes in this cohort's expectations as they progress through pregnancy.Practical implicationsThis paper provides maternity wear retail brands and designers a foundation for product development and marketing geared toward this large cohort.Originality/valueThe study is the first to inquire about Gen Z's outlook on pregnancy, specifically their envisioned changes to each body area and the role of maternity garments to fulfill needs and concerns.

The effect of intellectual property treaties on international innovation collaboration: a study based on USPTO patents during 1976–2017

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
JianQin Xiang ◽  
Feicheng Ma ◽  
Haiyan Wang
Keyword(s):  
Intellectual Property ◽  
The United States ◽  
Content Type ◽  
Global Innovation ◽  
Collaboration Environment ◽  
International Patent ◽  
Record Data ◽  
Innovation Cooperation ◽  
States Patent

PurposeStudies have indicated that international innovation collaboration has promoted technology transfer and knowledge spillover between countries. The conclusion of various international intellectual property (IP) treaties has played an essential role in optimizing the international innovation and collaboration environment. This study investigates the effect of IP treaties on international innovation collaboration and whether international IP treaties can promote collaboration between a country and other economies in the world.Design/methodology/approachAfter collecting and extracting the patent record data from the United States Patent and Trademark Office (USPTO), a final dataset of 3,213,626 cooperative patents and 465,236 pairs of collaborations between two countries or regions is established. Based on the international patent collaboration data of 192 countries during 1976–2017, the changes in patent collaboration indicators after these countries joined 23 IP treaties are analyzed.FindingsInternational IP treaties have significantly increased the number of patent cooperation countries of a country and its importance in international cooperation networks. The role of IP treaties is more manifested by the increased opportunities for a country's international innovation cooperation than its influence on global innovation; this is of extreme significance for developing countries to introduce advanced technologies.Originality/valueGinarte and Park (1997) have confirmed that IP treaties have helped to raise the level of IP protection. In this study, the increase in the degree centrality of the international innovation network is evidence of IP treaties to promote innovation cooperation. For a developing country, joining an intellectual property treaty may strengthen intellectual property protection and optimize its own international innovation cooperation methods.

The role of agency costs in the voluntary adoption of XBRL-based financial reporting

2020 ◽  
Vol 16 (5) ◽  
pp. 599-622
Author(s):  
Mehdi Khedmati ◽  
Farshid Navissi ◽  
Mohammed Aminu Sualihu ◽  
Zakiya Tofik-Abu
Keyword(s):  
United States ◽  
Financial Reporting ◽  
Agency Costs ◽  
The United States ◽  
Matched Pair ◽  
Alternative Measure ◽  
Content Type ◽  
Using Data ◽  
Voluntary Adoption

PurposeThe purpose of this paper is to examine whether and how firm's agency costs played a role in the voluntary adoption of the eXtensible Business Reporting Language (XBRL) under the SEC's voluntary filing program (VFP) that encouraged the voluntary adoption of the XBRL.Design/methodology/approachThis study employs a logistics regression and a sample of 140 firms that voluntarily participated in the VFP during its entire existence in the United States, and 140 matched-pair counterparts that did not voluntarily adopt the XBRL to investigate the role of agency costs in the voluntary adoption of XBRL-based financial reporting.FindingsWe find evidence consistent with the conjecture that a firm's low magnitude of agency costs plays a significant motivating role in the voluntary adoption of XBRL-based financial reporting. Our results continue to hold after using an alternative measure of agency costs and conducting two-stage least squares regressions. Supplementing these results, the study also shows that the level of agency costs of voluntary XBRL adopters remains statistically unchanged after the adoption while the level of agency costs associated with the firms that did not participate in SEC's VFP significantly decline after the adoption during the XBRL mandate.Practical implicationsThe findings of this study suggest that based on a firm's level of agency costs, regulators and policymakers, especially those in countries that are yet to mandate XBRL reporting, can, in advance, identify firms that are more likely to comply with their new financial reporting initiatives.Originality/valueThis paper provides first evidence on the role of agency costs in the voluntary adoption of XBRL using data from the United States.

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 Role of Antilipopolysaccharide Antibodies in Serum Bactericidal Activity against Salmonella enterica Serovar Typhimurium in Healthy Adults and Children in the United States

2013 ◽  
Vol 20 (10) ◽  
pp. 1491-1498 ◽  
Author(s):  
Estela Trebicka ◽  
Susan Jacob ◽  
Waheed Pirzai ◽  
Bryan P. Hurley ◽  
Bobby J. Cherayil
Keyword(s):  
United States ◽  
Bactericidal Activity ◽  
Salmonella Enterica ◽  
The United States ◽  
Healthy Children ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTRecent observations from Africa have rekindled interest in the role of serum bactericidal antibodies in protecting against systemic infection withSalmonella entericaserovar Typhimurium. To determine whether the findings are applicable to other populations, we analyzed serum samples collected from healthy individuals in the United States. We found that all but 1 of the 49 adult samples tested had robust bactericidal activity againstS. Typhimurium in a standardin vitroassay. The activity was dependent on complement and could be reproduced by immunoglobulin G (IgG) purified from the sera. The bactericidal activity was inhibited by competition with soluble lipopolysaccharide (LPS) fromS. Typhimurium but not fromEscherichia coli, consistent with recognition of a determinant in the O-antigen polysaccharide. Sera from healthy children aged 10 to 48 months also had bactericidal activity, although it was significantly less than in the adults, correlating with lower levels of LPS-specific IgM and IgG. The lone sample in our collection that lacked bactericidal activity was able to inhibit killing ofS. Typhimurium by the other sera. The inhibition correlated with the presence of an LPS-specific IgM and was associated with decreased complement deposition on the bacterial surface. Our results indicate that healthy individuals can have circulating antibodies to LPS that either mediate or inhibit killing ofS. Typhimurium. The findings contrast with the observations from Africa, which linked bactericidal activity to antibodies against anS. Typhimurium outer membrane protein and correlated the presence of inhibitory anti-LPS antibodies with human immunodeficiency virus infection.

scholarly journals Regulatory roles of differentially expressed MicroRNAs in metabolic processes in negative Lens-induced myopia Guinea pigs

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Dadong Guo ◽  
Meihua Ding ◽  
Xiaoli Song ◽  
Yuanyuan Sun ◽  
Guoping Li ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Signaling Pathways ◽  
Guinea Pigs ◽  
Messenger Rna ◽  
Differentially Expressed ◽  
Metabolic Processes ◽  
Ppar Signaling ◽  
Vision Defects ◽  
Guinea Pig Model

Abstract Background Myopia is one of the most common vision defects worldwide. microRNAs can regulate the target gene expression, influencing the development of diseases. Results To investigate the alterations of microRNA profiling in negative lens-induced myopia (NLIM) guinea pigs and to explore the regulatory role of microRNAs in the occurrence and the development of myopia, we first established the NLIM guinea pig model after induction for 2 weeks. Further, we isolated sclera to purify total messenger RNA (mRNA) in both NLIM and NLIM fellow sclera. Using next generation sequencing technique and bioinformatics analysis, we identified the differentially expressed microRNAs in NLIM guinea pigs, performed the bioinformatics annotation for the differentially expressed microRNAs, and validated the expression of differentially expressed microRNAs. As a result, we successfully established an NLIM model in guinea pigs, identified 27 differentially expressed microRNAs in NLIM guinea pig sclera, including 10 upregulated and 17 downregulated microRNAs. The KEGG annotation showed the main signaling pathways were closely associated with PPAR signaling, pyruvate and propanoate metabolisms, and TGF-beta signaling pathways. Conclusions Our findings indicate that the development of myopia is mainly involved in the disorder of metabolic processes in NLIM guinea pigs. The PPAR signaling, pyruvate and propanoate metabolism pathways may play roles in the development of myopia.

scholarly journals Comparison of Molecular Subtyping and Antimicrobial Resistance Detection Methods Used in a Large Multistate Outbreak of Extensively Drug-Resistant Campylobacter jejuni Infections Linked to Pet Store Puppies

2020 ◽  
Vol 58 (10) ◽  
Author(s):  
Lavin A. Joseph ◽  
Louise K. Francois Watkins ◽  
Jessica Chen ◽  
Kaitlin A. Tagg ◽  
Christy Bennett ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Campylobacter Jejuni ◽  
Multilocus Sequence Typing ◽  
The United States ◽  
Sequence Type ◽  
Outbreak Detection ◽  
Detection Methods ◽  
Drug Resistant ◽  
Molecular Subtyping ◽  
Content Type

ABSTRACT Campylobacter jejuni is a leading cause of enteric bacterial illness in the United States. Traditional molecular subtyping methods, such as pulsed-field gel electrophoresis (PFGE) and 7-gene multilocus sequence typing (MLST), provided limited resolution to adequately identify C. jejuni outbreaks and separate out sporadic isolates during outbreak investigations. Whole-genome sequencing (WGS) has emerged as a powerful tool for C. jejuni outbreak detection. In this investigation, 45 human and 11 puppy isolates obtained during a 2016–2018 outbreak linked to pet store puppies were sequenced. Core genome multilocus sequence typing (cgMLST) and high-quality single nucleotide polymorphism (hqSNP) analysis of the sequence data separated the isolates into the same two clades containing minor within-clade differences; however, cgMLST analysis does not require selection of an appropriate reference genome, making the method preferable to hqSNP analysis for Campylobacter surveillance and cluster detection. The isolates were classified as sequence type 2109 (ST2109)—a rarely seen MLST sequence type. PFGE was performed on 38 human and 10 puppy isolates; PFGE patterns did not reliably predict clustering by cgMLST analysis. Genetic detection of antimicrobial resistance determinants predicted that all outbreak-associated isolates would be resistant to six drug classes. Traditional antimicrobial susceptibility testing (AST) confirmed a high correlation between genotypic and phenotypic antimicrobial resistance determinations. WGS analysis linked C. jejuni isolates in humans and pet store puppies even when canine exposure information was unknown, aiding the epidemiological investigation during the outbreak. WGS data were also used to quickly identify the highly drug-resistant profile of these outbreak-associated C. jejuni isolates.

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