scholarly journals Analysis of the Small RNA Transcriptional Response in Multidrug-Resistant Staphylococcus aureus after Antimicrobial Exposure

2013 ◽  
Vol 57 (8) ◽  
pp. 3864-3874 ◽  
Author(s):  
Benjamin P. Howden ◽  
Marie Beaume ◽  
Paul F. Harrison ◽  
David Hernandez ◽  
Jacques Schrenzel ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Expression Profiles ◽  
Critical Role ◽  
Nonnegative Matrix ◽  
Transcriptional Response ◽  
Antibiotic Exposure ◽  
Data Set ◽  
Remarkable Feature ◽  
Content Type

ABSTRACTThe critical role of noncoding small RNAs (sRNAs) in the bacterial response to changing conditions is increasingly recognized. However, a specific role for sRNAs during antibiotic exposure has not been investigated inStaphylococcus aureus. Here, we used Illumina RNA-Seq to examine the sRNA response of multiresistant sequence type 239 (ST239)S. aureusafter exposure to four antibiotics (vancomycin, linezolid, ceftobiprole, and tigecycline) representing the major classes of antimicrobials used to treat methicillin-resistantS. aureus(MRSA) infections. We identified 409 potential sRNAs and then compared global sRNA and mRNA expression profiles at 2 and 6 h, without antibiotic exposure and after exposure to each antibiotic, for a vancomycin-susceptible strain (JKD6009) and a vancomycin-intermediate strain (JKD6008). Exploration of this data set by multivariate analysis using a novel implementation of nonnegative matrix factorization (NMF) revealed very different responses for mRNA and sRNA. Where mRNA responses clustered with strain or growth phase conditions, the sRNA responses were predominantly linked to antibiotic exposure, including sRNA responses that were specific for particular antibiotics. A remarkable feature of the antimicrobial response was the prominence of antisense sRNAs to genes encoding proteins involved in protein synthesis and ribosomal function. This study has defined a large sRNA repertoire in epidemic ST239 MRSA and shown for the first time that a subset of sRNAs are part of a coordinated transcriptional response to specific antimicrobial exposures inS. aureus. These data provide a framework for interrogating the role of staphylococcal sRNAs in antimicrobial resistance and exploring new avenues for sRNA-based antimicrobial therapies.

scholarly journals Impact of the Novel Prophage ϕSA169 on Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Liang Li ◽  
Genzhu Wang ◽  
Yi Li ◽  
Patrice Francois ◽  
Arnold S. Bayer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Hot Spot ◽  
Critical Role ◽  
Bacteriophage Therapy ◽  
Methicillin Resistant ◽  
Content Type ◽  
Antimicrobial Resistance Genes

ABSTRACT Persistent methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections are life-threatening syndromes with few therapeutic options. The potential impact of bacteriophages on the persistent outcome has not been well studied. In this study, we investigated the role of a novel prophage (ϕSA169) in MRSA persistence by using a lysogen-free clinically resolving bacteremia (RB) isolate and comparing it to a derivative which was obtained by infecting the RB strain with ϕSA169, which has been lysogenized in a clinical persistent MRSA bacteremia (PB) isolate. Similar to the PB isolate, the ϕSA169-lysogenized RB strain exhibited well-defined in vitro and in vivo phenotypic and genotypic signatures related to the persistent outcome, including earlier activation of global regulators (i.e., sigB, sarA, agr RNAIII, and sae); higher expression of a critical purine biosynthesis gene, purF; and higher growth rates accompanied by lower ATP levels and vancomycin (VAN) susceptibility and stronger δ-hemolysin and biofilm formation versus its isogenic parental RB isolate. Notably, the contribution of ϕSA169 in persistent outcome with VAN treatment was confirmed in an experimental infective endocarditis model. Taken together, these results indicate the critical role of the prophage ϕSA169 in persistent MRSA endovascular infections. Further studies are needed to identify the mechanisms of ϕSA169 in mediating the persistence, as well as establishing the scope of impact, of this prophage in other PB strains. IMPORTANCE Bacteriophages are viruses that invade the bacterial host, disrupt bacterial metabolism, and cause the bacterium to lyse. Because of its remarkable antibacterial activity and unique advantages over antibiotics, for instance, bacteriophage is specific for one species of bacteria and resistance to phage is less common than resistance to antibiotics. Indeed, bacteriophage therapy for treating infections due to multidrug-resistant pathogens in humans has become a research hot spot. However, it is also worth considering that bacteriophages are transferable and could cotransfer host chromosomal genes, e.g., virulence and antimicrobial resistance genes, while lysogenizing and integrating into the bacterial chromosome (prophage), thus playing a role in bacterial evolution and virulence. In the current study, we identified a novel prophage, ϕSA169, from a clinical persistent MRSA bacteremia isolate, and we determined that ϕSA169 mediated well-defined in vitro and in vivo phenotypic and genotypic signatures related to the persistent outcome, which may represent a unique and important persistent mechanism(s).

scholarly journals GSDMD contributes to host defence against Staphylococcus aureus skin infection by suppressing the Cxcl1–Cxcr2 axis

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Zhen-Zhen Liu ◽  
Yong-Jun Yang ◽  
Feng-Hua Zhou ◽  
Ke Ma ◽  
Xiao-Qi Lin ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Skin Infection ◽  
Bacterial Colonization ◽  
Critical Role ◽  
Host Defence ◽  
Skin Damage ◽  
Microbial Infection ◽  
Caspase 1 ◽  
Deficient Mice

AbstractGasdermin D (GSDMD), a member of the gasdermin protein family, is a caspase substrate, and its cleavage is required for pyroptosis and IL-1β secretion. To date, the role and regulatory mechanism of GSDMD during cutaneous microbial infection remain unclear. Here, we showed that GSDMD protected against Staphylococcus aureus skin infection by suppressing Cxcl1–Cxcr2 signalling. GSDMD deficiency resulted in larger abscesses, more bacterial colonization, exacerbated skin damage, and increased inflammatory cell infiltration. Although GSDMD deficiency resulted in defective IL-1β production, the critical role of IL-1β was counteracted by the fact that Caspase-1/11 deficiency also resulted in less IL-1β production but did not aggravate disease severity during S. aureus skin infection. Interestingly, GSDMD-deficient mice had increased Cxcl1 secretion accompanied by increased recruitment of neutrophils, whereas Caspase-1/11-deficient mice presented similar levels of Cxcl1 and neutrophils as wild-type mice. Moreover, the absence of GSDMD promoted Cxcl1 secretion in bone marrow-derived macrophages induced by live, dead, or different strains of S. aureus. Corresponding to higher transcription and secretion of Cxcl1, enhanced NF-κB activation was shown in vitro and in vivo in the absence of GSDMD. Importantly, inhibiting the Cxcl1–Cxcr2 axis with a Cxcr2 inhibitor or anti-Cxcl1 blocking antibody rescued host defence defects in the GSDMD-deficient mice. Hence, these results revealed an important role of GSDMD in suppressing the Cxcl1–Cxcr2 axis to facilitate pathogen control and prevent tissue damage during cutaneous S. aureus infection.

scholarly journals A novel ferroptosis related gene signature is associated with prognosis in patients with ovarian serous cystadenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhixiang Yu ◽  
Haiyan He ◽  
Yanan Chen ◽  
Qiuhe Ji ◽  
Min Sun
Keyword(s):  
Cox Regression ◽  
Expression Profiles ◽  
Critical Role ◽  
Gene Signature ◽  
Cancer Genome ◽  
Training Data ◽  
Hub Genes ◽  
Validation Data ◽  
Data Set ◽  
Cox Regression Analysis

AbstractOvarian cancer (OV) is a common type of carcinoma in females. Many studies have reported that ferroptosis is associated with the prognosis of OV patients. However, the mechanism by which this occurs is not well understood. We utilized Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) to identify ferroptosis-related genes in OV. In the present study, we applied Cox regression analysis to select hub genes and used the least absolute shrinkage and selection operator to construct a prognosis prediction model with mRNA expression profiles and clinical data from TCGA. A series of analyses for this signature was performed in TCGA. We then verified the identified signature using International Cancer Genome Consortium (ICGC) data. After a series of analyses, we identified six hub genes (DNAJB6, RB1, VIMP/ SELENOS, STEAP3, BACH1, and ALOX12) that were then used to construct a model using a training data set. The model was then tested using a validation data set and was found to have high sensitivity and specificity. The identified ferroptosis-related hub genes might play a critical role in the mechanism of OV development. The gene signature we identified may be useful for future clinical applications.

Market responsiveness: antecedents and the moderating role of external supply chain integration

2017 ◽  
Vol 32 (1) ◽  
pp. 30-45 ◽  
Author(s):  
Tuan Luu
Keyword(s):  
Supply Chain ◽  
Supply Chain Integration ◽  
Manufacturing Companies ◽  
Data Set ◽  
Content Type ◽  
Business Context ◽  
Market Responsiveness ◽  
Positive Effect ◽  
Ambidextrous Leadership

Purpose The interaction between opening and closing behaviors of ambidextrous leadership produces “change” force throughout the organization in proactive response to market forces. This research aims to assess the role of ambidextrous leadership in fostering entrepreneurial orientation (EO) and market responsiveness. The research also seeks an insight into how external supply chain integration moderates the positive effect of EO on market responsiveness. Design/methodology/approach Research data were collected from 327 meso-level managers and 517 subordinates from chemical manufacturing companies in the Vietnam business context. Findings Research findings shed light on the positive effect of ambidextrous leadership on EO, which in turn contributes to market responsiveness. The moderation role that external supply chain integration plays on the EO–market responsiveness linkage was also grounded on the data set. Originality/value Through the identification of the predictive roles of ambidextrous leadership and EO for market responsiveness, the current research indicates the convergence between leadership, EO and market responsiveness research streams.

Understanding destination evangelism: a social media viewpoint

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Purvendu Sharma
Keyword(s):  
Social Media ◽  
Information Seeking ◽  
Structural Equation ◽  
Structural Equation Models ◽  
Critical Role ◽  
Content Type ◽  
Mediating Role ◽  
Information Seeking Behaviors ◽  
Role Of Information

PurposeThe present research aims to introduce and understand the promising nature of destination evangelism in the context of social media-based tourism communities (SMTCs). Further, factors that influence evangelism and information-seeking behaviors on SMTCs are examined.Design/methodology/approachA conceptual model is developed that features an interplay of destination distinctiveness, destination evangelism, travel commitment and information-seeking engagement. Data were collected from 215 active users of SMTCs and analyzed using structural equation models.FindingsThe research findings indicate that destination distinctiveness and information-seeking positively lead to destination evangelism. Information-seeking is found to mediate the relationship between (1) destination evangelism and travel commitment and (2) destination evangelism and distinctiveness.Research limitations/implicationsThe research offers meaningful insights into exploring constituents of destination evangelism. The research also understands and highlights the critical role of information-seeking engagement about distinct destinations.Practical implicationsThis research highlights key areas to build, improve and inspire destination evangelism on SMTCs.Originality/valueThis study offers a fresh contribution to tourism literature by investigating destination evangelism and its drivers. This is explained by closely uniting vital research streams of evangelism, tourism and engagement. It further highlights the dual mediating role of information seeking, suggesting that these engagements are critical to evangelizing destinations.

The effect of industry association on firm innovation in Chinese private ventures

2019 ◽  
Vol 57 (9) ◽  
pp. 2414-2435
Author(s):  
Wenge Zhang ◽  
Jun Li ◽  
Yiyuan Mai
Keyword(s):  
Moderating Effects ◽  
Firm Level ◽  
Firm Innovation ◽  
Data Set ◽  
Industry Association ◽  
Content Type ◽  
Emerging Industries ◽  
Practical Implications ◽  
Firm Learning

Purpose The purpose of this paper is to examine the relationship between industry association membership and firm innovation in Chinese private ventures. A secondary objective is to investigate potential moderating effects of firm learning practices and founder characteristics on the above relationship, and to draw out implications for policymakers and practitioners. Design/methodology/approach The paper utilizes data from a sample of 567 Chinese entrepreneurial firms operating in 9 designated emerging industries. Hierarchical regression models were employed to analyze the effect of industry association membership on firm innovation, and the potential moderating effects. A 2SLS procedure was adopted to control for potential endogeneity issue. Supplemental analyses were conducted to ensure the robustness of the findings. Findings The paper provides empirical insights about how industry association membership, along with firm learning practice and founder leadership, affect firm innovation in Chinese private ventures in emerging industries. It suggests that industry association membership positively affects firm innovation. Further, there is a three-way interaction effect of industry association membership, learning practice and founder power on innovation. Research limitations/implications Due to the design of the data set, there are some limitations. First, the study only considered whether a firm belongs to an industry association, but not the nature of such membership (length, firm status in the association, etc.). Second, the cross-sectional design may limit the power of the study to make casual implications about the tested relationships. Practical implications The paper provides important practical implications for policymakers and entrepreneurs in China. In general, the results suggest that private ventures pursuing innovation in emerging industries can benefit from industry associations, and entrepreneurs shall actively engage in firm-level and personal-level learning. For policymakers, the study suggests that to foster innovation in an emerging industry, special attention shall be paid to building necessary institutional support to develop and to strengthen the role of industry association in the industry. Originality/value This paper fulfills an important gap in the literature in that it is one of the first, which investigates the role of the industry association in firm innovation, especially in a non-western context. This paper provides new insights into the role of industry association and firm innovation in an under-researched developing economy context.

scholarly journals The Staphylococcus aureus KdpDE Two-Component System Couples Extracellular K+Sensing and Agr Signaling to Infection Programming

2011 ◽  
Vol 79 (6) ◽  
pp. 2154-2167 ◽  
Author(s):  
Ting Xue ◽  
Yibo You ◽  
De Hong ◽  
Haipeng Sun ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Uptake System ◽  
Main Function ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Virulence Regulator ◽  
External K

ABSTRACTThe Kdp system is widely distributed among bacteria. InEscherichia coli, the Kdp-ATPase is a high-affinity K+uptake system and its expression is activated by the KdpDE two-component system in response to K+limitation or salt stress. However, information about the role of this system in many bacteria still remains obscure. Here we demonstrate that KdpFABC inStaphylococcus aureusis not a major K+transporter and that the main function of KdpDE is not associated with K+transport but that instead it regulates transcription for a series of virulence factors through sensing external K+concentrations, indicating that this bacterium might modulate its infectious status through sensing specific external K+stimuli in different environments. Our results further reveal thatS. aureusKdpDE is upregulated by the Agr/RNAIII system, which suggests that KdpDE may be an important virulence regulator coordinating the external K+sensing and Agr signaling during pathogenesis in this bacterium.

Institutional effect on born global firms in China: the role of Sun Tzu’s The Art of War strategies

2016 ◽  
Vol 10 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Man Zhang ◽  
Qian Gao ◽  
Jane V. Wheeler ◽  
Jungsook Kwon
Keyword(s):  
Emerging Markets ◽  
Institutional Environment ◽  
Critical Role ◽  
Born Global ◽  
Internationalization Process ◽  
Content Type ◽  
International Performance ◽  
The Relationship ◽  
Born Global Firms

Purpose – This paper aims to investigate the role of Sun Tzu’s significant strategies on the relationship between the institutional environment and international performance of Chinese born global firms, a type of small- and medium-sized enterprise (SME) characterized by the company’s limited resources and its early efforts to internationalize. Design/methodology/approach – The methodology is based on a multi-case analysis of interviews conducted with four chosen born global firms, coupled with public database and Web site searches. Through the use of qualitative methods, propositions were developed. Findings – This paper provides insights regarding how the institutional environment, both formal and informal, has a strong positive relationship with born global firm’s international performance. Moreover, Sun Tzu’s significant strategies play a critical role in the internationalization process of born global firms in emerging markets. Originality/value – Although existing studies discuss the application of Eastern philosophical strategies adopted by firms in emerging markets, to the best of our knowledge, this is one of the earliest studies which evaluates the moderation effect of Sun Tzu’s significant strategies on the relationship between institutional environment and business performance. The paper contributes to scholarly discourse on the influencing factors of born global firm’s internationalization process. It also has practical relevance to international entrepreneurs and SMEs from emerging markets.

scholarly journals Credit composition and income inequality in Vietnam: an empirical analysis

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Le Quoc Hoi ◽  
Hương Lan Trần
Keyword(s):  
Income Inequality ◽  
Educational Level ◽  
Generalized Method Of Moments ◽  
Institutional Quality ◽  
Primary Data ◽  
Data Set ◽  
Content Type ◽  
Private Credit ◽  
The Impact

PurposeThis paper aims to examine the credit composition and income inequality reduction in Vietnam. In particular, the authors focus on the distinction between policy and commercial credits and investigate whether these two types of credit had adverse effects on income inequality. The authors also examine whether the impact of policy credit on income inequality is conditioned by the educational level and institutional quality.Design/methodology/approachThe authors use the primary data set, which contains a panel of 60 provinces collected from the General Statistics Office of Vietnam from 2002 to 2016. The authors employ the generalized method of moments to solve the endogenous problem.FindingsThe authors show that while commercial credit increases income inequality, policy credit contributes to reducing income inequality in Vietnam. In addition, we provide evidence that the institutional quality and educational level condition the impact of policy credit on income inequality. Based on the findings, the paper implies that it was not the size of the private credit but its composition that mattered in reducing income inequality, due to the asymmetric effects of different types of credit.Originality/valueThis is the first study that examines the links between the two components of credit and income inequality as well as constraints of the links. The authors argue that analyzing the separate effects of commercial and policy credits is more important for explaining the role of credit in income inequality than the size of total credit.

scholarly journals Causal Role of Single Nucleotide Polymorphisms within themprFGene of Staphylococcus aureus in Daptomycin Resistance

2013 ◽  
Vol 57 (11) ◽  
pp. 5658-5664 ◽  
Author(s):  
Soo-Jin Yang ◽  
Nagendra N. Mishra ◽  
Aileen Rubio ◽  
Arnold S. Bayer
Keyword(s):  
Staphylococcus Aureus ◽  
Single Nucleotide Polymorphisms ◽  
Point Mutations ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Content Type ◽  
Reading Frame ◽  
A Charge

ABSTRACTSingle nucleotide polymorphisms (SNPs) within themprFopen reading frame (ORF) have been commonly observed in daptomycin-resistant (DAPr)Staphylococcus aureusstrains. Such SNPs are usually associated with a gain-in-function phenotype, in terms of either increased synthesis or enhanced translocation (flipping) of lysyl-phosphatidylglycerol (L-PG). However, it is unclear if suchmprFSNPs are causal in DAPrstrains or are merely a biomarker for this phenotype. In this study, we used an isogenic set ofS. aureusstrains: (i) Newman, (ii) its isogenic ΔmprFmutant, and (iii) several intransplasmid complementation constructs, expressing either a wild-type or point-mutated form of themprFORF cloned from two isogenic DAP-susceptible (DAPs)-DAPrstrain pairs (616-701 and MRSA11/11-REF2145). Complementation of the ΔmprFstrain with singly point-mutatedmprFgenes (mprFS295LormprFT345A) revealed that (i) individual and distinct point mutations within themprFORF can recapitulate phenotypes observed in donor strains (i.e., changes in DAP MICs, positive surface charge, and cell membrane phospholipid profiles) and (ii) these gain-in-function SNPs (i.e., enhanced L-PG synthesis) likely promote reduced DAP binding toS. aureusby a charge repulsion mechanism. Thus, for these two DAPrstrains, the definedmprFSNPs appear to be causally related to this phenotype.

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