scholarly journals Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

2016 ◽  
Vol 84 (8) ◽  
pp. 2198-2208 ◽  
Author(s):  
Colleen R. Eade ◽  
Chien-Che Hung ◽  
Brian Bullard ◽  
Geoffrey Gonzalez-Escobedo ◽  
John S. Gunn ◽  
...  

Salmonellaspp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded withinSalmonellapathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activatorhilDand to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant toSalmonellapathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressingSalmonellapathogenicity.

2022 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Robert J. Pidduck

Purpose Drawing on the “shocks to the system” concept in image theory, a mid-range theoretical model is developed to illuminate understanding on why cross-cultural experience is so conducive to stimulating entrepreneurship yet has remained largely unexplained at the individual level.Design/methodology/approach The novel idea is put forth that experience of foreignness, in itself, can be harnessed as a powerful cognitive resource for entrepreneurship – particularly the nascent stages of new venture development. Providing cross-cultural exposures arouse “self-image shocks”, they manifest over time as skill clusters that reflect the sensing, seizing and transforming capabilities at the heart of entrepreneurship. This paper's pivot helps delineate a common mechanism to explain how a diverse range of seemingly disparate cross-cultural experiences can be processed in a way that enhances entrepreneurial pursuits.Findings The insights of this paper reinforce the need for educators and policymakers to encourage and provide opportunities for aspiring entrepreneurs to engage in cross-cultural and overseas exposures as they are influential for stimulating each of the core sets of entrepreneurial capabilities. The model and synthesis table also help to practically unpack how to design and plan such cultural experiences to optimize the enduring entrepreneurial advantages.Originality/value The author turns a long-standing assumption surrounding cultural differences in entrepreneurship on its head. The shocks and tensions arising from intercultural interactions are not always inevitable liabilities to be “managed away” or attenuated. Rather, cross-cultural experience can be explicitly leveraged as an asset for nascent venturing as the juxtapositions they evoke provide both proximal and distal enhancements to ways in which entrepreneurs think and develop skills at the core of venturing.


2015 ◽  
Vol 198 (4) ◽  
pp. 604-614 ◽  
Author(s):  
Leah Schwiesow ◽  
Hanh Lam ◽  
Petra Dersch ◽  
Victoria Auerbuch

Many Gram-negative pathogens express a type III secretion (T3SS) system to enable growth and survival within a host. The three human-pathogenicYersiniaspecies,Y. pestis,Y. pseudotuberculosis, andY. enterocolitica, encode the Ysc T3SS, whose expression is controlled by an AraC-like master regulator called LcrF. In this review, we discuss LcrF structure and function as well as the environmental cues and pathways known to regulate LcrF expression. Similarities and differences in binding motifs and modes of action between LcrF and thePseudomonas aeruginosahomolog ExsA are summarized. In addition, we present a new bioinformatics analysis that identifies putative LcrF binding sites withinYersiniatarget gene promoters.


2017 ◽  
Author(s):  
Mohit S. Verma ◽  
Michael J. Fink ◽  
Gabriel L Salmon ◽  
Nadine Fornelos ◽  
Takahiro E. Ohara ◽  
...  

Two biological activities of butyrate in the colon (suppression of proliferation of colonic epithelial stem cells and inflammation) correlate with inhibition of histone deacetylases. Cellular and biochemical studies of molecules similar in structure to butyrate, but different in molecular details (functional groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation) demonstrated that these activities were sensitive to molecular structure, and were compatible with the hypothesis that butyrate acts by binding to the Zn<sup>2+</sup> in the catalytic site of histone deacetylases. Structure-activity relationships drawn from a set of 36 compounds offer a starting point for the design of new compounds targeting the inhibition of histone deacetylases. The observation that butyrate was more potent than other short-chain fatty acids is compatible with the hypothesis that crypts evolved (at least in part), to separate stem cells at the base of crypts from butyrate produced by commensal bacteria.


2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.


2017 ◽  
Vol 31 (2) ◽  
pp. 253-268 ◽  
Author(s):  
Sophie Soklaridis ◽  
Ayelet Kuper ◽  
Cynthia R. Whitehead ◽  
Genevieve Ferguson ◽  
Valerie H. Taylor ◽  
...  

Purpose The purpose of this paper is to examine the experiences of gender bias among women hospital CEOs and explore to what these female leaders attribute their success within a male-dominated hospital executive leadership milieu. Design/methodology/approach This qualitative study involved 12 women hospital CEOs from across Ontario, Canada. Purposeful sampling techniques and in-depth qualitative interview methods were used to facilitate discussion around experiences of gender and leadership. Findings Responses fell into two groups: the first group represented the statement “Gender inequality is alive and well”. The second group reflected the statement “Gender inequity is not significant, did not happen to me, and things are better now”. This group contained a sub-group with no consciousness of systemic discrimination and that claimed having no gendered experiences in their leadership journey. The first group described gender issues in various contexts, from the individual to the systemic. The second group was ambivalent about gender as a factor impacting leadership trajectories. Originality/value Representations of women’s leadership have become detached from feminism, with major consequences for women. This study reveals how difficult it is for some women CEOs to identify gender bias. The subtle everyday norms and practices within the workplace make it difficult to name and explain gender bias explicitly and may explain the challenges in understanding how it might affect a woman’s career path.


2015 ◽  
Vol 19 (3) ◽  
pp. 433-455 ◽  
Author(s):  
Christina Ling-hsing Chang ◽  
Tung-Ching Lin

Purpose – The purpose of the study is to focus on the enhancement of knowledge management (KM) performance and the relationship between organizational culture and KM process intention of individuals because of the diversity of organizational cultures (which include results-oriented, tightly controlled, job-oriented, closed system and professional-oriented cultures). Knowledge is a primary resource in organizations. If firms are able to effectively manage their knowledge resources, then a wide range of benefits can be reaped such as improved corporate efficiency, effectiveness, innovation and customer service. Design/methodology/approach – The survey methodology, which has the ability to enhance generalization of results (Dooley, 2001), was used to collect the data utilized in the testing of the research hypotheses. Findings – Results- and job-oriented cultures have positive effects on employee intention in the KM process (creation, storage, transfer and application), whereas a tightly controlled culture has negative effects. Research limitations/implications – However, it would have been better to use a longitudinal study to collect useful long-term data to understand how the KM process would be influenced when organizational culture dimensions are changed through/by management. This is the first limitation of this study. According to Mason and Pauleen (2003), KM culture is a powerful predictor of individual knowledge-sharing behavior, which is not included in this study. Thus, this is the second limitation of this paper. Moreover, national culture could be an important issue in the KM process (Jacks et al., 2012), which is the third limitation of this paper for not comprising it. Practical implications – In researchers’ point of view, results- and job-oriented cultures have positive effects, whereas a tightly controlled culture has a negative effect on the KM process intention of the individual. These findings provide evidences that challenge the perspective of Kayworth and Leidner (2003) on this issue. As for practitioners, management has a direction to modify their organizational culture to improve the performance of KM process. Social implications – Both behavioral and value perspectives of the organizational cultural dimensions (results-oriented, tightly control, job-oriented, sociability, solidarity, need for achievement and democracy) should be examined to ascertain their effects firstly on KM culture and then on the KM process intention of the individual. It is hoped that the current study will spawn future investigations that lead to the development of an integrated model which includes organizational culture, KM culture and the KM process intention of the individual. Originality/value – The results-oriented, loosely controlled and job-oriented cultures will improve the effectiveness of the KM process and will also increase employees’ satisfaction and willingness to stay with the organization.


2020 ◽  
Vol 11 (3) ◽  
pp. 447-460
Author(s):  
Nan Hua

Purpose This paper aims to examine the impacts of IT capabilities on hotel competitiveness. Design/methodology/approach This study adapts and extends Hua et al. (2015) and O’Neill et al. (2008) by incorporating the specific measures of IT expenditures as proxies for the relevant IT capabilities to explore the impacts of IT capabilities on hotel competitiveness. Findings This study finds that expenditures on IT Labor, IT Systems and IT Websites exert different impacts on hotel competitiveness. In addition, IT capabilities exert both contemporary and lagged effects on hotel competitiveness. Originality/value This study is the first that uses financial data to capture direct measures of individual IT capabilities and tests the individual impacts of IT capabilities on hotel competitiveness from both contemporaneous and lagged perspectives. It uses a large same store sample of hotels in the USA from 2011 to 2017; as a result, the study results can be reasonably representative of the hotel population in the USA.


mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Egon A. Ozer ◽  
Lauren L. Prister ◽  
Shaohui Yin ◽  
Billy H. Ward ◽  
Stanimir Ivanov ◽  
...  

ABSTRACT Gene diversification is a common mechanism pathogens use to alter surface structures to aid in immune avoidance. Neisseria gonorrhoeae uses a gene conversion-based diversification system to alter the primary sequence of the gene encoding the major subunit of the pilus, pilE. Antigenic variation occurs when one of the nonexpressed 19 silent copies donates part of its DNA sequence to pilE. We have developed a method using Pacific Biosciences (PacBio) amplicon sequencing and custom software to determine pilin antigenic variation frequencies. The program analyzes 37 variable regions across the strain FA1090 1-81-S2 pilE gene and can be modified to determine sequence variation from other starting pilE sequences or other diversity generation systems. Using this method, we measured pilin antigenic variation frequencies for various derivatives of strain FA1090 and showed we can also analyze pilin antigenic variation frequencies during macrophage infection. IMPORTANCE Diversity generation systems are used by many unicellular organism to provide subpopulations of cell with different properties that are available when needed. We have developed a method using the PacBio DNA sequencing technology and a custom computer program to analyze the pilin antigenic variation system of the organism that is the sole cause of the sexually transmitted infection, gonorrhea.


2019 ◽  
Vol 201 (17) ◽  
Author(s):  
Dragutin J. Savic ◽  
Scott V. Nguyen ◽  
Kimberly McCullor ◽  
W. Michael McShan

ABSTRACTA large-scale genomic inversion encompassing 0.79 Mb of the 1.816-Mb-longStreptococcus pyogenesserotype M49 strain NZ131 chromosome spontaneously occurs in a minor subpopulation of cells, and in this report genetic selection was used to obtain a stable lineage with this chromosomal rearrangement. This inversion, which drastically displaces theorisite relative to the terminus, changes the relative length of the replication arms so that one replichore is approximately 0.41 Mb while the other is about 1.40 Mb in length. Genomic reversion to the original chromosome constellation is not observed in PCR-monitored analyses after 180 generations of growth in rich medium. Compared to the parental strain, the inversion surprisingly demonstrates a nearly identical growth pattern in the first phase of the exponential phase, but differences do occur when resources in the medium become limited. When cultured separately in rich medium during prolonged stationary phase or in an experimental acute infection animal model (Galleria mellonella), the parental strain and the invertant have equivalent survival rates. However, when they are coincubated together, bothin vitroandin vivo, the survival of the invertant declines relative to the level for the parental strain. The accompanying aspect of the study suggests that inversions taking place nearoriCalways happen to secure the linkage oforiCto DNA sequences responsible for chromosome partition. The biological relevance of large-scale inversions is also discussed.IMPORTANCEBased on our previous work, we created to our knowledge the largest asymmetric inversion, covering 43.5% of theS. pyogenesgenome. In spite of a drastic replacement of origin of replication and the unbalanced size of replichores (1.4 Mb versus 0.41 Mb), the invertant, when not challenged with its progenitor, showed impressive vitality for growthin vitroand in pathogenesis assays. The mutant supports the existing idea that slightly deleterious mutations can provide the setting for secondary adaptive changes. Furthermore, comparative analysis of the mutant with previously published data strongly indicates that even large genomic rearrangements survive provided that the integrity of theoriCand the chromosome partition cluster is preserved.


2019 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Maria Elo ◽  
Leo-Paul Dana

Purpose The purpose of this paper is to explore how entrepreneurship traditions evolve in diaspora. Design/methodology/approach A qualitative multiple case study examining the role of diaspora embeddedness, extended family, ethno-religious-, cultural- and social ties and relevant structures shaping diaspora entrepreneurship. Findings The authors found that social ties and diaspora embeddedness create dynamism fostering entrepreneurial identity as a part of the Bukharian culture, and as a preferred career option in the context of Bukharian Jews in diaspora. Diasporic family businesses are products of culture and tradition that migrate to new locations with families and communities, not as disconnected business entities. Research limitations/implications The ways in which families nurture a highly entrepreneurial culture that transfers across generations and contexts are context-specific and not per se generalizable to other diasporas. Practical implications Diasporans often continue their traditions and become again entrepreneurs after their settlement, or they may generate hybrid, circular solutions that allow them to employ their competences in the new contexts or connecting various contexts. This calls for transnational entrepreneurship-policymaking. Social implications Time changes diasporas. A long-term commitment to the business environment evolves and reduces the mobility of the individual diasporan; typically the children of these migrants become more integrated and develop divergent career paths. Hence, their plans are not necessarily including family entrepreneurship creating a challenge for continuation of the original culture of entrepreneurship. Originality/value Despite a notable tradition in Jewish studies, there is limited research on Jewish entrepreneurial diaspora and its contemporary entrepreneurial identity and tradition. Furthermore, the population of Bukharian Jews is an unknown and under-explored highly entrepreneurial group that may offer instrumental views to larger diasporic audiences being concerned about maintaining notions of ethnic heritage and identity.


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