scholarly journals Staphylococcus aureus Arsenal To Conquer the Lower Respiratory Tract

mSphere ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Mariane Pivard ◽  
Karen Moreau ◽  
François Vandenesch

ABSTRACT Staphylococcus aureus is both a commensal and a pathogenic bacterium for humans. Its ability to induce severe infections is based on a wide range of virulence factors. S. aureus community-acquired pneumonia (SA-CAP) is rare and severe, and the contribution of certain virulence factors in this disease has been recognized over the past 2 decades. First, the factors involved in metabolism adaptation are crucial for S. aureus survival in the lower respiratory tract, and toxins and enzymes are required for it to cross the pulmonary epithelial barrier. S. aureus subsequently faces host defense mechanisms, including the epithelial barrier, but most importantly the immune system. Here, again, S. aureus uses myriad virulence factors to successfully escape from the host’s defenses and takes advantage of them. The impact of S. aureus virulence, combined with the collateral damage caused by an overwhelming immune response, leads to severe tissue damage and adverse clinical outcomes. In this review, we summarize step by step all of the S. aureus factors implicated in CAP and described to date, and we provide an outlook for future research.

2012 ◽  
Vol 57 (3) ◽  
pp. 1163-1168 ◽  
Author(s):  
John M. Boyce ◽  
Olivia-Fabiola Pop ◽  
Odaliz Abreu-Lanfranco ◽  
Whitney Y. Hung ◽  
Ann Fisher ◽  
...  

ABSTRACTHealthcare-associated pneumonia (HCAP) guidelines recommend de-escalating initial antibiotic therapy based on results from lower-respiratory-tract cultures. In the absence of adequate lower respiratory cultures, physicians are sometimes reluctant to discontinue empirical vancomycin, which is given for suspected methicillin-resistantStaphylococcus aureus(MRSA) HCAP. We evaluated a strategy of discontinuing vancomycin if both nasal and throat cultures were negative for MRSA when lower-respiratory-tract cultures were not available. An antimicrobial stewardship team identified patients receiving empirical vancomycin for suspected or proven HCAP but for whom adequate lower-respiratory-tract cultures were not available. Nasal and throat swab specimens were obtained and plated on MRSA selective media. If both nasal and throat MRSA cultures were negative, the stewardship team recommended discontinuation of empirical vancomycin. Demographic and clinical aspects, a clinical pulmonary infection score (CPIS) on the day of the stewardship recommendation, and mortality of patients for whom vancomycin was discontinued were obtained by retrospective chart review. A convenience sample of 91 patients with nasal and throat cultures negative for MRSA in the absence of adequate respiratory cultures had empirical vancomycin therapy discontinued. A retrospective review revealed that 88 (97%) patients had a CPIS of ≤6 on the day of the stewardship recommendation. In-hospital mortality (7.7%) was similar to that of a previous study of de-escalation of antibiotics in pneumonia patients without adequate cultures. In the absence of adequate lower-respiratory-tract cultures, it is reasonable to discontinue empirical vancomycin HCAP therapy in patients with negative MRSA nasal and throat cultures and a CPIS of <6.


2019 ◽  
Vol 40 (2) ◽  
pp. 356-372 ◽  
Author(s):  
Peter Hosie ◽  
Piyush Sharma ◽  
Russel P.J. Kingshott

Purpose The purpose of this paper is to extend the “Happy-Performing Managers” thesis to show that managers’ job-related affective well-being and affective job satisfaction mediate the impact of their role stressors (ambiguity, conflict and overload) on their contextual job performance. Design/methodology/approach Results from an online survey of 305 managers from the private, public and third sectors in Western Australian support most of the hypotheses. The psychometric properties of all the scales were analysed using confirmatory factor analysis and the conceptual model was tested using structural equation modelling. Findings Role stressors have a direct negative effect on the managers’ affective well-being and affective job satisfaction, which, in turn, mediate the negative effects of the three role stressors on the managers’ contextual performance. Research limitations/implications Conceptual and managerial contributions along with methodological limitations and future research directions are discussed. Originality/value Contemporary managers face a wide range of intrinsic and extrinsic role and environmental stressors. This research suggests that organisations may need to redesign manager roles to reduce their role stressors (ambiguity, conflict and overload) in order to optimise their contextual performance.


mSphere ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Brittney D. Gimza ◽  
Maria I. Larias ◽  
Bridget G. Budny ◽  
Lindsey N. Shaw

ABSTRACT A primary function of the extracellular proteases of Staphylococcus aureus is to control the progression of infection by selectively modulating the stability of virulence factors. Consequently, a regulatory network exists to titrate protease abundance/activity to influence the accumulation, or lack thereof, of individual virulence factors. Herein, we comprehensively map this system, exploring the regulation of the four protease loci by known and novel factors. In so doing, we determined that seven major elements (SarS, SarR, Rot, MgrA, CodY, SaeR, and SarA) form the primary network of control, with the latter three being the most powerful. We note that expression of aureolysin is largely repressed by these factors, while the spl operon is subject to the strongest upregulation of any protease loci, particularly by SarR and SaeR. Furthermore, when exploring scpA expression, we find it to be profoundly influenced in opposing fashions by SarA (repressor) and SarR (activator). We also present the screening of >100 regulator mutants of S. aureus, identifying 7 additional factors (ArgR2, AtlR, MntR, Rex, XdrA, Rbf, and SarU) that form a secondary circuit of protease control. Primarily, these elements serve as activators, although we reveal XdrA as a new repressor of protease expression. With the exception or ArgR2, each of the new effectors appears to work through the primary network of regulation to influence protease production. Collectively, we present a comprehensive regulatory circuit that emphasizes the complexity of protease regulation and suggest that its existence speaks to the importance of these enzymes to S. aureus physiology and pathogenic potential. IMPORTANCE The complex regulatory role of the proteases necessitates very tight coordination and control of their expression. While this process has been well studied, a major oversight has been the consideration of proteases as a single entity rather than as 10 enzymes produced from four different promoters. As such, in this study, we comprehensively characterized the regulation of each protease promoter, discovering vast differences in the way each protease operon is controlled. Additionally, we broaden the picture of protease regulation using a global screen to identify novel loci controlling protease activity, uncovering a cadre of new effectors of protease expression. The impact of these elements on the activity of proteases and known regulators was characterized by producing a comprehensive regulatory circuit that emphasizes the complexity of protease regulation in Staphylococcus aureus.


2021 ◽  
Vol 89 (4) ◽  
Author(s):  
Duah Alkam ◽  
Piroon Jenjaroenpun ◽  
Aura M. Ramirez ◽  
Karen E. Beenken ◽  
Horace J. Spencer ◽  
...  

ABSTRACT Mutation of purR was previously shown to enhance the virulence of Staphylococcus aureus in a murine sepsis model, and this cannot be fully explained by increased expression of genes within the purine biosynthesis pathway. Rather, the increased production of specific S. aureus virulence factors, including alpha toxin and the fibronectin-binding proteins, was shown to play an important role. Mutation of purR was also shown previously to result in increased abundance of SarA. Here, we demonstrate by transposon sequencing that mutation of purR in the USA300 strain LAC increases fitness in a biofilm while mutation of sarA has the opposite effect. Therefore, we assessed the impact of sarA on reported purR-associated phenotypes by characterizing isogenic purR, sarA, and sarA/purR mutants. The results confirmed that mutation of purR results in increased abundance of alpha toxin, protein A, the fibronectin-binding proteins, and SarA, decreased production of extracellular proteases, an increased capacity to form a biofilm, and increased virulence in an osteomyelitis model. Mutation of sarA had the opposite effects on all of these phenotypes and, other than bacterial burdens in the bone, all of the phenotypes of sarA/purR mutants were comparable to those of sarA mutants. Limiting the production of extracellular proteases reversed all of the phenotypes of sarA mutants and most of those of sarA/purR mutants. We conclude that a critical component defining the virulence of a purR mutant is the enhanced production of SarA, which limits protease production to an extent that promotes the accumulation of critical S. aureus virulence factors.


2015 ◽  
Vol 29 (4) ◽  
pp. 255-267 ◽  
Author(s):  
Richard Nicholls ◽  
Marwa Gad Mohsen

Purpose – This study aims to explore the relevance of customer age differences (CADs) in the context of customer-to-customer interaction (CCI) within various service domains. It provides a thematic framework for understanding CAD-related CCI and critically identifies new directions for research into CAD-related CCI. Design/methodology/approach – Using a narrative literature review approach, different perspectives in the literature on age differences and CCI are analysed towards highlighting and emphasising valuable new themes. Findings – Three coherent domains: the desire for social contact; fellow customer behaviour; and social identity issues are identified to interconnect a fragmented diversity of literature. Many themes for future research directions in the study of CAD-related CCI are identified. Research limitations/implications – Whilst a wide selection of literature sources are critically reviewed, the fragmented nature of the literature on age differences and CCI prevents the review covering all publications. Practical implications – The paper provides service marketing managers and scholars with strategic CCI insights into better serving a diverse age range of customers. These insights will undoubtedly stimulate timely investigation of new avenues to enhance service customer compatibility and satisfaction in increasingly age-diverse societies. Originality/value – This paper provides the first overview of a wide range of strategic considerations aimed at explaining the impact of CADs on CCI in service environments. Essentially, the paper elaborates opportunities and challenges in CAD-related CCI as critical themes for further investigations.


2014 ◽  
Vol 82 (4) ◽  
pp. 1424-1435 ◽  
Author(s):  
Andy Weiss ◽  
J. Antonio Ibarra ◽  
Jessica Paoletti ◽  
Ronan K. Carroll ◽  
Lindsey N. Shaw

ABSTRACTIn Gram-positive bacteria, and particularly theFirmicutes, the DNA-dependent RNA polymerase (RNAP) complex contains an additional subunit, termed the δ factor, or RpoE. This enigmatic protein has been studied for more than 30 years for various organisms, but its function is still not well understood. In this study, we investigated its role in the major human pathogenStaphylococcus aureus. We showed conservation of important structural regions of RpoE inS. aureusand other species and demonstrated binding to core RNAP that is mediated by the β and/or β′ subunits. To identify the impact of the δ subunit on transcription, we performed transcriptome sequencing (RNA-seq) analysis and observed 191 differentially expressed genes in therpoEmutant. Ontological analysis revealed, quite strikingly, that many of the downregulated genes were known virulence factors, while several mobile genetic elements (SaPI5 and prophage ϕSA3usa) were strongly upregulated. Phenotypically, therpoEmutant had decreased accumulation and/or activity of a number of key virulence factors, including alpha toxin, secreted proteases, and Panton-Valentine leukocidin (PVL). We further observed significantly decreased survival of the mutant in whole human blood, increased phagocytosis by human leukocytes, and impaired virulence in a murine model of infection. Collectively, our results demonstrate that the δ subunit of RNAP is a critical component of theS. aureustranscription machinery and plays an important role during infection.


mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Brittney D. Gimza ◽  
Jessica K. Jackson ◽  
Andrew M. Frey ◽  
Bridget G. Budny ◽  
Dale Chaput ◽  
...  

ABSTRACT Staphylococcus aureus controls the progression of infection through the coordinated production of extracellular proteases, which selectively modulate virulence determinant stability. This is evidenced by our previous finding that a protease-null strain has a hypervirulent phenotype in a murine model of sepsis, resulting from the unchecked accumulation of virulence factors. Here, we dissect the individual roles of these proteases by constructing and assessing the pathogenic potential of a combinatorial protease mutant library. When strains were constructed bearing increasing numbers of secreted proteases, we observed a variable impact on infectious capacity, where some exhibited hypervirulence, while others phenocopied the wild-type. The common thread for hypervirulent strains was that each lacked both aureolysin and staphopain A. Upon assessment, we found that the combined loss of these two enzymes alone was necessary and sufficient to engender hypervirulence. Using proteomics, we identified a number of important secreted factors, including SPIN, LukA, Sbi, SEK, and PSMα4, as well as an uncharacterized chitinase-related protein (SAUSA300_0964), to be overrepresented in both the aur scpA and the protease-null mutants. When assessing the virulence of aur scpA SAUSA300_0964 and aur scpA lukA mutants, we found that hypervirulence was completely eliminated, whereas aur scpA spn and aur scpA sek strains elicited aggressive infections akin to the protease double mutant. Collectively, our findings shed light on the influence of extracellular proteases in controlling the infectious process and identifies SAUSA300_0964 as an important new component of the S. aureus virulence factor arsenal. IMPORTANCE A key feature of the pathogenic success of S. aureus is the myriad virulence factors encoded within its genome. These are subject to multifactorial control, ensuring their timely production only within an intended infectious niche. A key node in this network of control is the secreted proteases of S. aureus, who specifically and selectively modulate virulence factor stability. In our previous work we demonstrated that deletion of all 10 secreted proteases results in hypervirulence, since virulence factors exist unchecked, leading to overly aggressive infections. Here, using a combinatorial collection of protease mutants, we reveal that deletion of aureolysin and staphopain A is necessary and sufficient to elicit hypervirulence. Using proteomic techniques, we identify the collection of virulence factors that accumulate in hypervirulent protease mutants, and demonstrate that a well-known toxin (LukA) and an entirely novel secreted element (SAUSA300_0964) are the leading contributors to deadly infections observed in protease-lacking strains.


2018 ◽  
Vol 60 (5) ◽  
pp. 375-388 ◽  
Author(s):  
Robert Griffiths ◽  
Jay Probert ◽  
Brendan Cropley

Purpose The purpose of this paper is to evaluate the impact of a foundation degree programme, delivered via a flipped university approach, on student learning, development and employability in the sector of football coaching and development. Design/methodology/approach A mixed-method design was adopted, whereby current (n=106) and graduate (n=41) students from the programme completed an online course evaluation questionnaire and then follow-up interviews were conducted with 12 of the initial sample to explore the impact of the programme in more detail. Findings Participants reported significant benefits of the flipped university approach on their career development, improvement in their inter- and intra-personal skills (e.g. communication, reflection, confidence) and the acquisition of industry relevant knowledge. Recommendations include a greater provision of tailored study support for individuals and broadening the coaching portfolio of students to help address the diversification in Football Community Trust remits. Research limitations/implications This study has indicated that new approaches to student learning and development are better suited to preparing young people for the industry in which they seek to gain employment post-education. Sampling a wider range of student perspectives qualitatively would have provided a more thorough insight into their experiences. However, this provides an avenue for future research that seeks to explore the mechanisms through which such approaches to learning facilitate development. Originality/value The novel flipped university concept is one that should be considered as a way of better educating and preparing students for employment in the sports industry. It is an approach that could be explored by a wide range of sectors as an alternative to both campus-based higher education and degree apprenticeships.


2017 ◽  
Vol 31 (3) ◽  
pp. 286-301 ◽  
Author(s):  
Sharlene Chadwick ◽  
Joanne Travaglia

Purpose During the past decade, there has been increased attention into bullying behaviours in workplaces. Research to date has varied in design, the definition of what constitutes bullying behaviour, as well as the methods used to collect data and measure bullying incidence and prevalence. Nonetheless, studies demonstrate that bullying is a significant issue, which warrants an increased research focus to develop greater understanding of the concept, its effects and implications in, and for, the workplace. The purpose of this paper is to focus on capturing a range of international and Australian literature regarding workplace bullying behaviours in a health context from a management perspective. As a result, this paper identified the gaps in the literature when expanded specifically to an Australian health context. Design/methodology/approach The purpose of this review is to summarise the existing literature, both internationally and in Australia which examines workplace bullying behaviours in a health context from a management perspective. This describes the review of the literature on workplace bullying in a health context undertaken from January to April 2014. The “Preferred Reporting Systematic Reviews and Meta-Analyses” method was used to structure the review, which covered a wide range of literature from databases including MEDLINE, Embase, CINAHL and InformIT, as well as reports, and grey literature. Findings The review included 62 studies that met the inclusion criteria and reported either: factors contributing to workplace bullying, at least one significant example of workplace bullying behaviour or the impact of workplace bullying behaviours in a health context. Originality/value There is limited data on workplace bullying behaviours in an Australian health context. The literature supports there is value in future research to develop consistent definitions, policies, procedures and frameworks, which could help to prevent or address workplace bullying behaviours based on work being undertaken internationally.


2021 ◽  
pp. 016264342198997
Author(s):  
Sojung Jung ◽  
Ciara Ousley ◽  
David McNaughton ◽  
Pamela Wolfe

In this meta-analytic review, we investigated the effects of technology supports on the acquisition of shopping skills for students with intellectual and developmental disabilities (IDD) between the ages of 5 and 24. Nineteen single-case experimental research studies, presented in 15 research articles, met the current study’s inclusion criteria and the What Works Clearinghouse (WWC) standards. An analysis of potential moderators was conducted, and we calculated effect sizes using Tau-U to examine the impact of age, diagnosis, and type of technology on the reported outcomes for the 56 participants. The results from the included studies provide evidence that a wide range of technology interventions had a positive impact on shopping performance. These positive effects were seen for individuals across a wide range of ages and disability types, and for a wide variety of shopping skills. The strongest effect sizes were observed for technologies that provided visual supports rather than just auditory support. We provide an interpretation of the findings, implications of the results, and recommended areas for future research.


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