scholarly journals Corynebacterium pseudodiphtheriticumExploitsStaphylococcus aureusVirulence Components in a Novel Polymicrobial Defense Strategy

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Britney L. Hardy ◽  
Seth W. Dickey ◽  
Roger D. Plaut ◽  
Daniel P. Riggins ◽  
Scott Stibitz ◽  
...  
Keyword(s):  
Nasal Cavity ◽  
Bactericidal Activity ◽  
Low Frequency ◽  
Opportunistic Pathogen ◽  
Commensal Bacteria ◽  
Nasal Colonization ◽  
Antimicrobial Compounds ◽  
Content Type ◽  
Corynebacterium Pseudodiphtheriticum ◽  
The Cost

ABSTRACTCommensal bacteria in the human nasal cavity are known to suppress opportunistic pathogen colonization by competing for limited space and nutrients. It has become increasingly apparent that some commensal bacteria also produce toxic compounds that directly inhibit or kill incoming competitors. Numerous studies suggest that microbial species-specific interactions can affect human nasal colonization by the opportunistic pathogenStaphylococcus aureus. However, the complex and dynamic molecular interactions that mediate these effects onS. aureusnasal colonization are often difficult to study and remain poorly understood. Here, we show thatCorynebacterium pseudodiphtheriticum, a common member of the normal nasal microbiota, mediates contact-independent bactericidal activity againstS. aureus, including methicillin-resistantS. aureus(MRSA). Bacterial interaction assays revealed thatS. aureusisolates that were spontaneously resistant toC. pseudodiphtheriticumkilling could be recovered at a low frequency. To better understand the pathways associated with killing and resistance, aS. aureustransposon mutant library was utilized to select for resistant mutant strains. We found that insertional inactivation ofagrC, which codes for the sensor kinase of the Agr quorum sensing (Agr QS) system that regulates expression of many virulence factors inS. aureus, conferred resistance to killing. Analysis of the spontaneously resistantS. aureusisolates revealed that each showed decreased expression of the Agr QS components. Targeted analysis of pathways regulated by Agr QS revealed that loss of the phenol-soluble modulins (PSMs), which are effectors of Agr QS, also conferred resistance to bactericidal activity. Transmission electron microscopy analysis revealed thatC. pseudodiphtheriticuminduced dramatic changes toS. aureuscell surface morphology that likely resulted in cell lysis. Taken together, these data suggest thatC. pseudodiphtheriticum-mediated killing ofS. aureusrequiresS. aureusvirulence components. WhileS. aureuscan overcome targeted killing, this occurs at the cost of attenuated virulence; loss of Agr QS activity would phenotypically resemble aS. aureuscommensal state that would be unlikely to be associated with disease. Commensal competition resulting in dampened virulence of the competitor may represent an exciting and unexplored possibility for development of novel antimicrobial compounds.IMPORTANCEWhile some individuals are nasally colonized withS. aureus, the underlying factors that determine colonization are not understood. There is increasing evidence that indicates that resident bacteria play a role; some commensal species can eradicateS. aureusfrom the nasal cavity. Among these,Corynebacterium pseudodiphtheriticumcan eliminateS. aureusfrom the human nose. We sought to understand this phenomenon at a molecular level and found thatC. pseudodiphtheriticumproduces a factor(s) that specifically killsS. aureus. While resistantS. aureusisolates were recovered at a low frequency, resistance came at the cost of attenuated virulence in these strains. Molecular dissection of the specific strategies used byC. pseudodiphtheriticumto killS. aureuscould lead to the development of novel treatments or therapies. Furthermore, commensal competition that requires virulence components of the competitor may represent an exciting and unexplored possibility for development of novel antimicrobial compounds.

scholarly journals Triclosan Promotes Staphylococcus aureus Nasal Colonization

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Adnan K. Syed ◽  
Sudeshna Ghosh ◽  
Nancy G. Love ◽  
Blaise R. Boles
Keyword(s):  
Staphylococcus Aureus ◽  
Risk Factor ◽  
Human Microbiome ◽  
Opportunistic Pathogen ◽  
Unintended Consequences ◽  
Nasal Colonization ◽  
Content Type ◽  
Test Population ◽  
Human Proteins ◽  
Nasal Secretions

ABSTRACT The biocide triclosan is used in many personal care products, including toothpastes, soaps, clothing, and medical equipment. Consequently, it is present as a contaminant in the environment and has been detected in some human fluids, including serum, urine, and milk. Staphylococcus aureus is an opportunistic pathogen that colonizes the noses and throats of approximately 30% of the population. Colonization with S. aureus is known to be a risk factor for several types of infection. Here we demonstrate that triclosan is commonly found in the nasal secretions of healthy adults and the presence of triclosan trends positively with nasal colonization by S. aureus. We demonstrate that triclosan can promote the binding of S. aureus to host proteins such as collagen, fibronectin, and keratin, as well as inanimate surfaces such as plastic and glass. Lastly, triclosan-exposed rats are more susceptible to nasal colonization with S. aureus. These data reveal a novel factor that influences the ability of S. aureus to bind surfaces and alters S. aureus nasal colonization. IMPORTANCE Triclosan has been used as a biocide for over 40 years, but the broader effects that it has on the human microbiome have not been investigated. We demonstrate that triclosan is present in nasal secretions of a large portion of a test population and its presence correlates with Staphylococcus aureus nasal colonization. Triclosan also promotes the binding of S. aureus to human proteins and increases the susceptibility of rats to nasal colonization by S. aureus. These findings are significant because S. aureus colonization is a known risk factor for the development of several types of infections. Our data demonstrate the unintended consequences of unregulated triclosan use and contribute to the growing body of research demonstrating inadvertent effects of triclosan on the environment and human health.

scholarly journals The Human Gut Microbial Metabolome Modulates Fungal Growth via the TOR Signaling Pathway

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Carlos García ◽  
Faiza Tebbji ◽  
Michelle Daigneault ◽  
Ning-Ning Liu ◽  
Julia R. Köhler ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inflammatory Diseases ◽  
Opportunistic Pathogen ◽  
Convincing Evidence ◽  
Commensal Bacteria ◽  
Bioactive Molecules ◽  
Mucosal Barrier ◽  
Content Type ◽  
Bowel Diseases ◽  
The One

ABSTRACT Candida albicans is a natural component of the human microbiota but also an opportunistic pathogen that causes life-threatening infections. The human gastrointestinal tract is the main reservoir of C. albicans, from where systemic infections originate as a consequence of the disruption of the intestinal mucosal barrier. Recent studies provided convincing evidence that overgrowth of C. albicans and other related species in the gut is predominantly associated with chronic intestinal inflammatory bowel diseases. Here, we showed, for the first time, the antagonistic interkingdom interactions between C. albicans and common intestinal commensal bacteria. From a therapeutic perspective, administering a defined bacterial community, such as the one described here with anti-Candida activity, could provide potential therapeutic protection against gastrointestinal inflammatory diseases. Candida albicans is well known as a major human fungal pathogen, but it is also a permanent resident of healthy gastrointestinal tracts. Recent studies have shown that the human gut microbial metabolome represents an interesting source of bioactive molecules with a significant degree of chemical diversity. Some of these bioactive molecules may have useful antivirulence activities. For instance, intestinal bacterial species belonging to the Lachnospiraceae family were found to secrete molecules that attenuate Salmonella pathogenicity and repress the expression of virulence genes. Here, we have investigated whether the microbial gut metabolome (GM) contains molecules that might promote the commensal lifestyle and/or inhibit the expression of virulence of C. albicans in the intestine. We found that metabolites from human feces inhibited the growth of C. albicans and other opportunistic yeasts. A genetic screen in C. albicans suggested that TOR is the molecular target of the antifungal molecule(s) of the GM. In addition, we found that the GM metabolites inhibit both C. albicans hyphal growth and the invasion of human enterocytes. The antigrowth and antivirulence activities were partially recapitulated by secretions from Roseburia spp. and Bacteroides ovatus strains, respectively. This study demonstrates that the antimicrobial activity of the GM can be extended to a eukaryotic pathogen, C. albicans, illuminating the antagonistic interkingdom interactions between a fungus and intestinal commensal bacteria. IMPORTANCE Candida albicans is a natural component of the human microbiota but also an opportunistic pathogen that causes life-threatening infections. The human gastrointestinal tract is the main reservoir of C. albicans, from where systemic infections originate as a consequence of the disruption of the intestinal mucosal barrier. Recent studies provided convincing evidence that overgrowth of C. albicans and other related species in the gut is predominantly associated with chronic intestinal inflammatory bowel diseases. Here, we showed, for the first time, the antagonistic interkingdom interactions between C. albicans and common intestinal commensal bacteria. From a therapeutic perspective, administering a defined bacterial community, such as the one described here with anti-Candida activity, could provide potential therapeutic protection against gastrointestinal inflammatory diseases.

Deployment of a charging network based on a cost-benefit model and the CFSFDP algorithm

Kybernetes ◽  
2019 ◽  
Vol 48 (9) ◽  
pp. 1989-2005
Author(s):  
Can Zhong Yao ◽  
Jie Luo
Keyword(s):  
Low Frequency ◽  
Cost Benefit ◽  
Growth Potential ◽  
Content Type ◽  
Gas Stations ◽  
Density Peaks ◽  
Use Efficiency ◽  
The Cost ◽  
Charging Stations ◽  
The Relationship

Purpose This research aims to focus on the problem of optimizing the layout of charging stations. Design/methodology/approach The authors estimate the total number of charging stations by the number of existing gas stations using clustering by fast search-and-find of density peaks (CFSFDP) algorithm. Findings This paper reveals the relationship between the distance and the population. Priority should be given to the short-distance and high-frequency travel charging needs in the city, followed by low frequency and travel, which can improve the use efficiency of the whole charging network. Originality/value First, the total number of charging stations is estimated by the number of existing gas stations. This method can fully consider the growth potential of charging vehicles instead of the traditional cars. Besides, the cost-benefit method is proposed to explore the marginal coverage distance of the city’s charging network and can be used to reveal the relationship between the distance and the population.

The cost-effectiveness of insulin analogs and regular insulin for diabetes control: a case study in Iran

2020 ◽  
Vol 33 (4/5) ◽  
pp. 323-331
Author(s):  
Mohsen pakdaman ◽  
Raheleh akbari ◽  
Hamid reza Dehghan ◽  
Asra Asgharzadeh ◽  
Mahdieh Namayandeh
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Regular Insulin ◽  
Diabetes Control ◽  
Diabetic Patients ◽  
Insulin Analogs ◽  
Content Type ◽  
Patients With Diabetes ◽  
The Government ◽  
The Cost

PurposeFor years, traditional techniques have been used for diabetes treatment. There are two major types of insulin: insulin analogs and regular insulin. Insulin analogs are similar to regular insulin and lead to changes in pharmacokinetic and pharmacodynamic properties. The purpose of the present research was to determine the cost-effectiveness of insulin analogs versus regular insulin for diabetes control in Yazd Diabetes Center in 2017.Design/methodology/approachIn this descriptive–analytical research, the cost-effectiveness index was used to compare insulin analogs and regular insulin (pen/vial) for treatment of diabetes. Data were analyzed in the TreeAge Software and a decision tree was constructed. A 10% discount rate was used for ICER sensitivity analysis. Cost-effectiveness was examined from a provider's perspective.FindingsQALY was calculated to be 0.2 for diabetic patients using insulin analogs and 0.05 for those using regular insulin. The average cost was $3.228 for analog users and $1.826 for regular insulin users. An ICER of $0.093506/QALY was obtained. The present findings suggest that insulin analogs are more cost-effective than regular insulin.Originality/valueThis study was conducted using a cost-effectiveness analysis to evaluate insulin analogs versus regular insulin in controlling diabetes. The results of study are helpful to the government to allocate more resources to apply the cost-effective method of the treatment and to protect patients with diabetes from the high cost of treatment.

scholarly journals Melanization in Cryptococcus neoformans Requires Complex Regulation

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Radames J. B. Cordero ◽  
Emma Camacho ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Defense Mechanisms ◽  
Environmental Stressors ◽  
Antimicrobial Compounds ◽  
Human Pathogen ◽  
Content Type ◽  
Signaling Mechanisms ◽  
Complex Regulation ◽  
Multiple Levels ◽  
Melanin Binding

ABSTRACT The fungal human pathogen Cryptococcus neoformans undergoes melanization in response to nutrient starvation and exposure to exogenous melanin precursors. Melanization protects the fungus against host defense mechanisms such as oxidative damage and other environmental stressors (e.g., heat/cold stress, antimicrobial compounds, ionizing radiation). Conversely, the melanization process generates cytotoxic intermediates, and melanized cells are potentially susceptible to overheating and to certain melanin-binding drugs. Despite the importance of melanin in C. neoformans biology, the signaling mechanisms regulating its synthesis are poorly understood. The recent report by D. Lee, E.-H. Jang, M. Lee, S.-W. Kim, et al. [mBio 10(5):e02267-19, 2019, https://doi.org/10.1128/mBio.02267-19] provides new insights into how C. neoformans regulates melanization. The authors identified a core melanin regulatory network consisting of transcription factors and kinases required for melanization under low-nutrient conditions. The redundant and epistatic connections of this melanin-regulating network demonstrate that C. neoformans melanization is complex and carefully regulated at multiple levels. Such complex regulation reflects the multiple functions of melanin in C. neoformans biology.

scholarly journals Research on comment target extracting in Chinese online shopping platform

2018 ◽  
Vol 2 (3) ◽  
pp. 247-258
Author(s):  
Zhishuo Liu ◽  
Qianhui Shen ◽  
Jingmiao Ma ◽  
Ziqi Dong
Keyword(s):  
Association Rule ◽  
Online Shopping ◽  
Low Frequency ◽  
Online Reviews ◽  
Content Type ◽  
Pos Tagging ◽  
Part Of Speech ◽  
Frequency Feature ◽  
Practical Implications ◽  
Data Reading

Purpose This paper aims to extract the comment targets in Chinese online shopping platform. Design/methodology/approach The authors first collect the comment texts, word segmentation, part-of-speech (POS) tagging and extracted feature words twice. Then they cluster the evaluation sentence and find the association rules between the evaluation words and the evaluation object. At the same time, they establish the association rule table. Finally, the authors can mine the evaluation object of comment sentence according to the evaluation word and the association rule table. At last, they obtain comment data from Taobao and demonstrate that the method proposed in this paper is effective by experiment. Findings The extracting comment target method the authors proposed in this paper is effective. Research limitations/implications First, the study object of extracting implicit features is review clauses, and not considering the context information, which may affect the accuracy of the feature excavation to a certain degree. Second, when extracting feature words, the low-frequency feature words are not considered, but some low-frequency feature words also contain effective information. Practical implications Because of the mass online reviews data, reading every comment one by one is impossible. Therefore, it is important that research on handling product comments and present useful or interest comments for clients. Originality/value The extracting comment target method the authors proposed in this paper is effective.

Evaluating the cost and benefits of earthquake protection of buildings

2018 ◽  
Vol 11 (2) ◽  
pp. 263-278 ◽  
Author(s):  
Benedetto Manganelli ◽  
Marco Vona ◽  
Pierfrancesco De Paola
Keyword(s):  
Real Estate ◽  
Seismic Risk ◽  
Risk Mitigation ◽  
Tax Incentives ◽  
Seismic Retrofitting ◽  
Content Type ◽  
Seismic Risk Mitigation ◽  
The Cost ◽  
Earthquake Protection ◽  
Real Estate Assets

Purpose The purpose of this study is the evaluation of the cost and benefits of earthquake protection of buildings to verify whether the legislative push, through tax incentives, will produce results and lead to a redevelopment of private real estate assets. Design/methodology/approach Through contingent valuation, this research aims to measure the propensity of homeowners to invest in the seismic security of their properties. The sample of homeowners was selected in a southern Italy city, which was characterized by a medium-high seismic hazard. The willingness to pay, once made independent from the family income, was compared with the actual cost of a seismic retrofitting technique to assess its cost-effectiveness. Findings The analysis developed on an example case shows that the economic sustainability of the intervention is only verified when considering the current tax incentives for this type of intervention. Practical implications Choosing to introduce a system to compulsory insurance against seismic risk could certainly be a strong incentive for the implementation of retrofitting interventions on private real estate assets. In this direction, investigations like this can be fundamental to establish the fair risk premium. Originality/value The need for effective seismic risk mitigation policies is also based on the growing awareness of the, often fatal, effects of seismic events, emphasized by the recent medium and high intensity events that hit Italy. The issue of the security of residential buildings is therefore a very topical issue in view of their high seismic vulnerability and the vast number of buildings requiring major seismic retrofitting. Therefore, the propensity of owners to intervene in improving the seismic performance of their properties can be crucial in seismic risk mitigation.

The impact of labor freedom on geographic cost of living differentials

2017 ◽  
Vol 6 (3) ◽  
pp. 385-395
Author(s):  
Richard Cebula ◽  
James E. Payne ◽  
Donnie Horner ◽  
Robert Boylan
Keyword(s):  
Labor Market ◽  
State Level ◽  
The State ◽  
Annual Data ◽  
Significant Finding ◽  
Cost Of Living ◽  
Content Type ◽  
The Usa ◽  
The Cost ◽  
The Impact

Purpose The purpose of this paper is to examine the impact of labor market freedom on state-level cost of living differentials in the USA using cross-sectional data for 2016 after allowing for the impacts of economic and quality of life factors. Design/methodology/approach The study uses two-stage least squares estimation controlling for factors contributing to cost of living differences across states. Findings The results reveal that an increase in labor market freedom reduces the overall cost of living. Research limitations/implications The study can be extended using panel data and alternative measures of labor market freedom. Practical implications In general, the finding that less intrusive government and greater labor freedom are associated with a reduced cost of living should not be surprising. This is because less government intrusion and greater labor freedom both inherently allow markets to be more efficient in the rationalization of and interplay with forces of supply and demand. Social implications The findings of this and future related studies could prove very useful to policy makers and entrepreneurs, as well as small business owners and public corporations of all sizes – particularly those considering either location in, relocation to, or expansion into other markets within the USA. Furthermore, the potential benefits of the National Right-to-Work Law currently under consideration in Congress could add cost of living reductions to the debate. Originality/value The authors extend the literature on cost of living differentials by investigating whether higher amounts of state-level labor market freedom act to reduce the states’ cost of living using the most recent annual data available (2016). That labor freedom has a systemic efficiency impact on the state-level cost of living is a significant finding. In our opinion, it is likely that labor market freedom is increasing the efficiency of labor market transactions in the production and distribution of goods and services, and acts to reduce the cost of living in states. In addition, unlike previous related studies, the authors investigate the impact of not only overall labor market freedom on the state-level cost of living, but also how the three sub-indices of labor market freedom, as identified and measured by Stansel et al. (2014, 2015), impact the cost of living state by state.

A new index to measure cost of living for expatriates in cities

2018 ◽  
Vol 28 (3) ◽  
pp. 295-317
Author(s):  
Khee Giap Tan ◽  
Nguyen Trieu Duong Luu ◽  
Le Phuong Anh Nguyen
Keyword(s):  
New York ◽  
Hong Kong ◽  
Quality Data ◽  
Cost Of Living ◽  
Content Type ◽  
Goods And Services ◽  
Commercial Research ◽  
The Cost ◽  
Cost Of Living Index ◽  
The City

Purpose Cost of living is an important consideration for the decision-making of expatriates and investment decisions of businesses. As competition between cities for talent and capital becomes global instead of national, the need for timely and internationally comparable information on global cities’ cost of living increases. While commercial research houses frequently publish cost of living surveys, these reports can be lacking in terms of scientific rigour. In this context, this paper aims to contribute to the literature by formulating a comprehensive and rigorous methodology to compare the cost of living for expatriates in 103 world’s major cities. Design/methodology/approach A cost of living index for expatriates composed of the ten consumption categories is constructed. The results from the study covers a study period from 2005 to 2014 in 103 cities. More than 280 individual prices of 165 goods and services have been compiled for each city in the calculation of the cost of living index for expatriates. New York has been chosen as the base city for the study, with other cities being benchmarked against it. A larger cost of living index for expatriates implies that the city is more expensive for expatriates to live in and vice versa. Findings While the authors generate the cost of living rankings for expatriates for 103 cities worldwide, in this paper, the authors focus on five key cities, namely, London, Hong Kong, Singapore, Tokyo and Zurich, as they are global financial centres. In 2013, the latest year for which data are available, Zurich was the most expensive for expatriates among the five cities, followed by Singapore, Tokyo, London and Hong Kong. These results pertain to the cost of living for expatriates, and cities compare very differently in terms of cost of living for ordinary residents, as ordinary residents follow different consumption patterns from expatriates. Originality/value Cost of living in the destination city is a major consideration for professionals who look to relocate, and organisations factor such calculations in their decisions to post employees overseas and design commensurate compensation packages. This paper develops a comprehensive and rigorous methodology for measuring and comparing cost of living for expatriates around the world. The value-addition lies in the fact that the authors are able to differentiate between expatriates and ordinary residents, which has not been done in the existing literature. They use higher quality data and generate an index that is not sensitive to the choice of base city.

scholarly journals Bactericidal Activity, Absence of Serum Effect, and Time-Kill Kinetics of Ceftazidime-Avibactam against β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa

2014 ◽  
Vol 58 (9) ◽  
pp. 5297-5305 ◽  
Author(s):  
Tiffany R. Keepers ◽  
Marcela Gomez ◽  
Chris Celeri ◽  
Wright W. Nichols ◽  
Kevin M. Krause
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Human Serum ◽  
Bactericidal Activity ◽  
Minimum Bactericidal Concentration ◽  
Wild Type ◽  
Content Type ◽  
Positive Isolate ◽  
New Treatment ◽  
Time Kill ◽  
Kinetics Of

ABSTRACTAvibactam, a non-β-lactam β-lactamase inhibitor with activity against extended-spectrum β-lactamases (ESBLs), KPC, AmpC, and some OXA enzymes, extends the antibacterial activity of ceftazidime against most ceftazidime-resistant organisms producing these enzymes. In this study, the bactericidal activity of ceftazidime-avibactam against 18Pseudomonas aeruginosaisolates and 15Enterobacteriaceaeisolates, including wild-type isolates and ESBL, KPC, and/or AmpC producers, was evaluated. Ceftazidime-avibactam MICs (0.016 to 32 μg/ml) were lower than those for ceftazidime alone (0.06 to ≥256 μg/ml) against all isolates except for 2P. aeruginosaisolates (1blaVIM-positive isolate and 1blaOXA-23-positive isolate). The minimum bactericidal concentration/MIC ratios of ceftazidime-avibactam were ≤4 for all isolates, indicating bactericidal activity. Human serum and human serum albumin had a minimal effect on ceftazidime-avibactam MICs. Ceftazidime-avibactam time-kill kinetics were evaluated at low MIC multiples and showed time-dependent reductions in the number of CFU/ml from 0 to 6 h for all strains tested. A ≥3-log10decrease in the number of CFU/ml was observed at 6 h for allEnterobacteriaceae, and a 2-log10reduction in the number of CFU/ml was observed at 6 h for 3 of the 6P. aeruginosaisolates. Regrowth was noted at 24 h for some of the isolates tested in time-kill assays. These data demonstrate the potent bactericidal activity of ceftazidime-avibactam and support the continued clinical development of ceftazidime-avibactam as a new treatment option for infections caused byEnterobacteriaceaeandP. aeruginosa, including isolates resistant to ceftazidime by mechanisms dependent on avibactam-sensitive β-lactamases.

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