Redirection of the Immune Response to Staphylococcus Aureus Biofilm Infection PDF Download

Author: Anna G Staudacher
Publisher:
ISBN:
Category :
Languages : en
Pages : 110

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Book Description
Staphylococcus aureus (S. aureus) is a leading cause of community- and healthcare-associated infections and has a propensity to form biofilms. Biofilm infections are recalcitrant to host immune-mediated clearance as well as antibiotics, making them exceptionally difficult to eradicate. The biofilm environment has been shown to skew the host immune response towards an anti-inflammatory phenotype, characterized by alternatively activated macrophages, recruitment of myeloid-derived suppressor cells (MDSCs), and minimal neutrophil and T cell infiltrates. Our laboratory has attempted to redirect the host immune response towards one that would favor bacterial clearance by employing strategies to augment pro-inflammatory mechanisms. One such approach was to utilize lipopolysaccharide (LPS), which was expected to promote pro-inflammatory activation of peripheral immune cells infiltrating the biofilm and subsequent clearance of infection. This theory was partially correct, as pro-inflammatory cytokines in the serum were significantly increased, and peripheral immune cells in the blood were more effective at killing S. aureus ex vivo following LPS treatment; however biofilm infection was exacerbated. Specifically, bacterial titers increased nearly 2-log with administration of LPS, and although infiltration of Ly6G+Ly6C+ MDSCs was decreased, a new population of Ly6GintLy6C+ cells appeared. Additionally, both Ly6G+Ly6C+ and Ly6GintLy6C+ populations were more suppressive with LPS treatment, partially explaining the expansion of S. aureus biofilm burdens. This study highlights the resilient nature of S. aureus biofilm infections to influence the immune response, particularly through MDSCs, even in the face of a strong pro-inflammatory stimulus. Gaining a better understanding of the mechanisms that cause this ineffective host immune response to staphylococcal biofilms is a necessary step towards eradicating these debilitating infections.

Author: Daniel Anibal Cantero Cajas
Publisher:
ISBN:
Category : Biofilms
Languages : en
Pages : 422

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Book Description
Chronic Rhinosinusitis (CRS) is the persistent and symptomatic inflammation of the mucosa of the nose and paranasal cavities. It is a prevalent condition severely affecting the quality of life of around 10% of the population in Western countries. Its pathogenesis involves environmental factors such as viruses or bacteria on predisposed hosts triggering local mucosal inflammation. Staphylococcus aureus (S. aureus) is the most common isolated bacterium in CRS and, when forming biofilms, increases its resistance to antibiotics, being correlated with recalcitrant cases and higher rates of mucosal inflammation. The local inflammation can be explained by virulence factors from S. aureus, and also by innate and adaptive immune mechanisms of the host immune response. Although some researchers have explored the late or adaptive immune response associated with S. aureus biofilms, less is known about the initial or innate immune response that S. aureus biofilms trigger in the mucosa. This thesis aimed to study part of the mucosal innate immune response to S. aureus biofilms. We have challenged human sinonasal tissues - from normal donors undergoing transnasal pituitary surgery - with S. aureus biofilms ex vivo using an explant model. This model mimics in vivo conditions because it allows biofilms to grow at the air-liquid interface. Also, the biofilm-mucosa interaction is more physiological than primary cell cultures, because the communication between different host cells is preserved in the explant model. After the interaction with S. aureus biofilms, explant tissues produced IL-6 and other cytokines polarised to a Th1/Th17 type of immune response. The observed Th1/Th17 immune response differs from previous reports in eosinophilic CRS patients with nasal polyps (CRSwNP) showing a predominant Th2 response. Apparently there is an evolution from early Th1/Th17 immune responses to late Th2 in S. aureus biofilm associated infections. The turning point between these two types of immune responses seems critical in CRS because it could explain the origin of the Th2 inflammation. In the future, the use of long-term animal models could help to illustrate the progression from an initial Th1/Th17 to a late Th2 type of immune response in the sinonasal mucosa. S. aureus biofilms also induced apoptosis in the mucosa as demonstrated by the up-regulation of cleaved caspase-3 in our settings. We also demonstrated the induction and activation of the Nod2 receptor and downstream pathway secondary to S. aureus biofilms. The Nod2 receptor recognises a small portion of peptidoglycan that is available during early phases of S. aureus biofilm formation. The role of Nod2 in CRS and biofilm infections should be evaluated in future studies. In conclusion, we demonstrated that early S. aureus biofilms induce a proinflammatory response in the sinonasal mucosa. This proinflammatory response seems to be crucial for biofilm attachment and persistence, and its modulation could represent an alternative to prevent S. aureus biofilm infections. Secreted staphylococcal products such as alpha ([alpha]) toxin and staphylococcal protein A (SpA) are two virulence factors critical during early biofilm growth. These proteins are also able to generate immune responses and represent targets for potential therapeutic intervention during biofilm infections in the sinonasal mucosa.

Author: Fabio Bagnoli
Publisher: Frontiers Media SA
ISBN: 2889742660
Category : Science
Languages : en
Pages : 281

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Topic Editors Dr. Bagnoli and Dr. Phogat are employed by GlaxoSmithKline plc. The other Topic Editors Declare no conflict of interest in relation to the Research Topic theme

Author: Talib Alboslemy
Publisher:
ISBN:
Category : Biofilms
Languages : en
Pages : 122

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Book Description
Complications arising from cutaneous and soft tissue infections with Staphylococcus aureus (S. aureus) are a major clinical problem due to the high incidence of these infections and the widespread emergence of antibiotic-resistant bacterial strains. In particular, S. aureus infection involving the formation of biofilm is clinically challenging due to antibiotic resistance and immune evasive characteristics of biofilm-associated infection. Accumulating evidences support that macrophages associated with S. aureus biofilms have decreased secretion of cytokines and chemokines, which might have contributed to the impaired bactericidal activity. A series of recent studies have demonstrated that S. aureus biofilms skew macrophage polarization towards an anti-inflammatory phenotype that persists bacterial survival. However, the detailed mechanism underlying the evasion of macrophage-mediated innate immune response against S. aureus biofilm is poorly understood. The central hypothesis of this study is that S. aureus biofilm environment skews macrophage polarization toward the anti-inflammatory phenotype by interfering with a pattern recognition receptor (PRR)-dependent positive regulatory mechanism or aberrantly amplifying a negative regulatory mechanism of NF-kB activation. In this study, using an in vitro model of murine macrophages exposed to the secreted factors from S. aureus biofilm, we have determined the impact of the S. aureus biofilms on macrophage-mediated innate immune response and elucidated its associated signaling mechanism. The major finding of this study is that S. aureus biofilm environment associated with alpha toxin skews macrophage polarization toward the anti-inflammatory phenotype by aberrantly increasing the expression of Krüppel-like factor 2 (KLF2) in macrophages, which in turn negatively regulate the activation of NF-kB pathways for host innate immune responses. Our study provides an important insight into the mechanism by which S. aureus biofilm impair macrophage-mediated innate immune defense functions and is the first to identify KLF2 in macrophage as a molecular target by S. aureus biofilm to evade innate immune attack by macrophages. Understanding the nature of host-microbial interactions, in particular in the context of the mechanisms used by S. aureus biofilm to evade host innate immune defense, is the key to develop an effective immunotherapy for combating infectious diseases. Our study provides a new opportunity for immunotherapy for targeting macrophage polarization toward the anti-biofilm phenotype by targeting KLF2 and its associated signalling in macrophages against S. aureus biofilm infection.

Author: Minh Giao Long Bui
Publisher:
ISBN:
Category : Biofilms
Languages : en
Pages : 277

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Book Description
Staphylococcus aureus has an incredible ability to survive, either by adapting to environmental conditions or defending against exogenous stresses. In part this ability is provided by the breadth of lifestyles or modes of growth S. aureus can adopt. Key to an understanding of chronic, persistent and relapsing S. aureus infections is determining the basis for their switch to quasi-dormant lifestyles. Across different bacterial species these alternative lifestyles form a population known as persister cells. It has been proposed that while within their host, a sub-population of S. aureus survives in host-generated and therapeutic antimicrobial stress by inducing biofilm growth on host tissue or by growing as Small Colony Variants (SCVs). These stresses include limited nutrition, reactive oxygen species, reactive nitrogen species, other toxic metabolites, cationic peptides, fluctuating pH and osmolarity, several antibiotics, and others that are generated from various host tissues and niches during an infection. In a multicellular biofilm, the metabolically quiescent bacterial community produces a highly protective extracellular polymeric substance (EPS). The EPS is variously composed of polysaccharides, extracellular DNA (eDNA), and protein, and its protection results in persistent bacterial infections. S. aureus forms biofilms in different human tissues, and to some degree the associated EPS has been studied. Alternatively, there exists a diversity of phenotypes and cell-types that translate to a particular bacterial lifestyle. In clinical settings, SCV of S. aureus have been observed for many years and when cultured, these cells are non-pigmented colonies ca. 10 times smaller than their counterparts on agar plates. Mutations in hemin and menadione biosynthesis (hemB and menA) have produced laboratory-generated SCVs and these and other mutations have been studied extensively. The presence of gentamicin has also been shown to impede S. aureus metabolism and results in SCVs. Both methods result in stable forms of SCV but are artificially generated. Various genotypic factors (single nucleotide polymorphisms, mutations, gene deletions) have been identified to attempt to characterize S. aureus SCVs as well as environmental stresses are also considered to be important inducers. Our project was aimed to investigate the lifestyle switching of S. aureus clinical isolates as a stress response to environmental stresses that help these organisms to survive. The results showed that S. aureus clinical isolates had relatively similar growth rates but were different in their response to chemical stresses. There were specific strains that responded to stresses by changing their lifestyles to form a biofilm and/or SCVs in harsh conditions (but still sub-lethal levels of stress) but not in lower levels of stress. These results implied that phenotype switching depends on bacterial and host factors and suggests some specific strains may possess a unique pathway involved in surviving when stressed. In addition, studying native characteristics of SCV has been problematic due to their reversion to the parental, rapid growing lifestyle. Using specific host-representative, steady-state growth conditions with low nutrients and growth rates over a prolonged time with methylglyoxal - a naturally resident chemical that is found in the host-pathogen environment, we uniquely induced a S. aureus clinical isolate (WCH-SK2) into a stable SCV cell-type. The stable SCV phenotype did not revert after numerous cycles of subculturing and analysis revealed it possessed a metabolic and surface profile different from either previously described SCV or biofilm cells. The existence of the stable SCVs was verified and its features were analyzed by genomic, transcriptomic and surface protein profile studies. Stable SCVs produced an extracellular matrix of protein and extracellular DNA; but not polysaccharide. Compared to its parental cell-type, the stable SCV cells increased expression of certain surface proteins (such as Ebh; host extracellular matrix binding protein homologue) and lantibiotic synthesis while down-regulating factors that stimulate the host immune response (leukocidins, capsule, carotenoids). This cell-type is consistent with a lifestyle protected by a matrix and hidden from immune responses. Genome sequencing revealed a set of genetic changes from the parental to stable SCV cell-type, including the transcription factors RsbB and MrgA, as well as a change in the methylome. Collectively, our data shows that there is heterogeneity within a S. aureus population as shown by a diverse scope of cell-types; by growing the cells in conditions that resemble long-term survival in the host, colonization or persistence, we have identified a previously unnoticed S. aureus lifestyle. These stable SCV are molecularly distinct in nature to SCV or biofilm cells and this cell-type provides a new understanding of S. aureus persistence in the host.

Author: Opeyemi O Ajayi
Publisher:
ISBN:
Category :
Languages : en
Pages : 460

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Bacterial cells, in nature, prefer to exist as a surface-attached coalescent community of slime-encased cells known as biofilms. This biofilm-forming existence offers several advantages to the cells, including evasion of host immune response, resistance to antimicrobials and antibiotics, communal expression of metabolites, and overall increased survivability in unfavorable environmental conditions. Biofilm formation has been observed for several species of bacteria across multiple scientific disciplines and affecting a wide variety of industries including the food industry, waste treatment, and healthcare. In healthcare settings, S. aureus is a major etiological agent of biofilm-based infections in humans. Furthermore, the hydrodynamic environment of the cardiovascular system complicates the eradication of biofilm-based infection due to metastasis of eroded cells to multiple infection sites. Therefore, remediation efforts of staphylococcal infections are aimed at the prevention and disruption of biofilm development.

Author: Semih Esin
Publisher: Frontiers Media SA
ISBN: 2889711331
Category : Medical
Languages : en
Pages : 134

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Author: John E. Bennett
Publisher: Elsevier Health Sciences
ISBN: 0323263739
Category : Medical
Languages : en
Pages : 5094

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Book Description
After thirty five years, Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 8th Edition is still the reference of choice for comprehensive, global guidance on diagnosing and treating the most challenging infectious diseases. Drs. John E. Bennett and Raphael Dolin along with new editorial team member Dr. Martin Blaser have meticulously updated this latest edition to save you time and to ensure you have the latest clinical and scientific knowledge at your fingertips. With new chapters, expanded and updated coverage, increased worldwide perspectives, and many new contributors, Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 8th Edition helps you identify and treat whatever infectious disease you see. Get the answers to any questions you have with more in-depth coverage of epidemiology, etiology, pathology, microbiology, immunology, and treatment of infectious agents than you’ll find in any other ID resource. Apply the latest knowledge with updated diagnoses and treatments for currently recognized and newly emerging infectious diseases, such as those caused by avian and swine influenza viruses. Put the latest knowledge to work in your practice with new or completely revised chapters on Influenza (new pandemic strains); New Middle East Respiratory Syndrome (MERS) Virus; Probiotics; Antibiotics for resistant bacteria; Antifungal drugs; New Antivirals for hepatitis B and C; Clostridium difficile treatment; Sepsis; Advances in HIV prevention and treatment; Viral gastroenteritis; Lyme Disease; Helicobacter pylori; Malaria; Infections in immunocompromised hosts; Immunization (new vaccines and new recommendations); and Microbiome. Benefit from fresh perspectives and expanded global insights from an expanded team of American and International contributors. Martin Blaser, MD, a leading expert and Muriel G. and George W. Singer Professional of Translational Medicine at New York University School of Medicine, joins veteran PPID editors John E. Bennett, MD, and Raphael Dolin, MD to continue a legacy of excellence. Find and grasp the information you need easily and rapidly with newly added chapter summaries.

Author: Shymaa Enany
Publisher: BoD – Books on Demand
ISBN: 953512983X
Category : Medical
Languages : en
Pages : 226

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Book Description
Staphylococcus aureus S. aureus is a growing issue both within hospitals and community because of its virulence determinants and the continuing emergence of new strains resistant to antimicrobiotics. In this book, we present the state of the art of S. aureus virulence mechanisms and antibiotic-resistance profiles, providing an unprecedented and comprehensive collection of up-to-date research about the evolution, dissemination, and mechanisms of different staphylococcal antimicrobial resistance patterns alongside bacterial virulence determinants and their impact in the medical field. We include several review chapters to allow readers to better understand the mechanisms of methicillin resistance, glycopeptide resistance, and horizontal gene transfer and the effects of alterations in S. aureus membranes and cell walls on drug resistance. In addition, we include chapters dedicated to unveiling S. aureus pathogenicity with the most current research available on S. aureus exfoliative toxins, enterotoxins, surface proteins, biofilm, and defensive responses of S. aureus to antibiotic treatment.

Author: Karen E. Nelson
Publisher: Springer Science & Business Media
ISBN: 1441970894
Category : Science
Languages : en
Pages : 302

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Book Description
The book brings a completely different perspective than available books by combining the information gained from the human genome with that derived from parallel metagenomic studies, and new results from investigating the effects of these microbes on the host immune system. Although there are a number of books that focus on the human genome that are currently available, there are no books that bring to the forefront the mix of the human genome and the genomes and metagenomes of the microbial species that live within and on us.