Environmental Determinants of Antibiotic Resistance and Virulence of Acinetobacter Baumannii and Development of Novel Molecular Tools for Genetic Manipulations of Acinetobacter Baumannii PDF Download
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Author: Pawuththuwadura Malaka Pulinda De Silva
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Acinetobacter baumannii is a notorious pathogen in health- care settings around the world, primarily due to its reduced susceptibility to antibiotics. A. baumanniiIt also shows impressive capabilities to adapt to harsh conditions in clinical settings, which contributes to its persistence in such conditions. Following their traditional role, the Two Component Systems (TCSs) present in A. baumannii play a crucial role in sensing and adapting to the changing environmental conditions. Out of the TCSs present in A. baumannii, AdeRS TCS has been shown to modulate a key RND efflux pump, AdeABC which can result in antibiotic resistance. In-frame deletion of adeRS resulted in reduced expression of AdeB as demonstrated previously confirming the regulatory role of AdeRS in expression of AdeABC. DFurther, deletion of adeRS affected biofilm formation and motility of A. baumannii demonstrating the multi-faceted nature of regulatory networks controlled by AdeRS. Interestingly, the adeRS deletion mutant was sensitive to saline stress and surface associated motility was adversely affected at higher NaCl concentrations suggesting that AdeRS could be a part of salinity stress adaptation in A. baumannii. Investigations into the adaptation of A. baumannii to incubation temperatures of 28 ̊C and 37 ̊C revealed potentially clinically relevant phenotypic changes. Specifically, motility was reduced at 28 ̊C while biofilm formation significantly increased at 28 ̊C. Proteomic analysis showed an upregulation of 366 proteins and downregulation of 263 proteins at 28 ̊C. An uncharacterized orphan response regulator, A1S_2006 displayed significantly higher expression levels in a MDR A. baumannii clinical isolate AB030. A deletion mutant of A1S_2006 displayed decreased biofilm formation, motility, and virulence in Galleria mellonella model. However, deletion of A1S_2006 resulted in significantly higher attachment of A. baumannii in A549 cells. RNA-Seq analysis of the deletion mutant revealed upregulation of 116 genes and downregulation of 42 genes. Finally, to address the lack of molecular tools available for genetic manipulations of A. baumannii, a set of novel mini-Tn7 based vectors were created by using apramycin and zeocin resistance markers to rejuvenate the current mini-Tn7 based vectors. These can be used for genetic manipulations in clinical isolates with reduced susceptibility to commonly used markers. These results show the role of environmental determinants in modulating clinically relevant characteristics of A. baumannii as well as adding new components to the molecular toolkit for A. baumannii.
Author: Pawuththuwadura Malaka Pulinda De Silva
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Acinetobacter baumannii is a notorious pathogen in health- care settings around the world, primarily due to its reduced susceptibility to antibiotics. A. baumanniiIt also shows impressive capabilities to adapt to harsh conditions in clinical settings, which contributes to its persistence in such conditions. Following their traditional role, the Two Component Systems (TCSs) present in A. baumannii play a crucial role in sensing and adapting to the changing environmental conditions. Out of the TCSs present in A. baumannii, AdeRS TCS has been shown to modulate a key RND efflux pump, AdeABC which can result in antibiotic resistance. In-frame deletion of adeRS resulted in reduced expression of AdeB as demonstrated previously confirming the regulatory role of AdeRS in expression of AdeABC. DFurther, deletion of adeRS affected biofilm formation and motility of A. baumannii demonstrating the multi-faceted nature of regulatory networks controlled by AdeRS. Interestingly, the adeRS deletion mutant was sensitive to saline stress and surface associated motility was adversely affected at higher NaCl concentrations suggesting that AdeRS could be a part of salinity stress adaptation in A. baumannii. Investigations into the adaptation of A. baumannii to incubation temperatures of 28 ̊C and 37 ̊C revealed potentially clinically relevant phenotypic changes. Specifically, motility was reduced at 28 ̊C while biofilm formation significantly increased at 28 ̊C. Proteomic analysis showed an upregulation of 366 proteins and downregulation of 263 proteins at 28 ̊C. An uncharacterized orphan response regulator, A1S_2006 displayed significantly higher expression levels in a MDR A. baumannii clinical isolate AB030. A deletion mutant of A1S_2006 displayed decreased biofilm formation, motility, and virulence in Galleria mellonella model. However, deletion of A1S_2006 resulted in significantly higher attachment of A. baumannii in A549 cells. RNA-Seq analysis of the deletion mutant revealed upregulation of 116 genes and downregulation of 42 genes. Finally, to address the lack of molecular tools available for genetic manipulations of A. baumannii, a set of novel mini-Tn7 based vectors were created by using apramycin and zeocin resistance markers to rejuvenate the current mini-Tn7 based vectors. These can be used for genetic manipulations in clinical isolates with reduced susceptibility to commonly used markers. These results show the role of environmental determinants in modulating clinically relevant characteristics of A. baumannii as well as adding new components to the molecular toolkit for A. baumannii.
Author: Santiago Castillo Ramírez
Publisher: Frontiers Media SA
ISBN: 288966824X
Category : Science
Languages : en
Pages : 229
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Book Description
Author: E. Bergogne-Berezin
Publisher: CRC Press
ISBN: 1000151727
Category : Medical
Languages : en
Pages : 290
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Book Description
Acinetobacter details the clinical aspects of this bacterium responsible for many infections in hospitalized patients. This reference explains the importance of these organisms, both from the patient's viewpoint and the economic perspective, and provides clinicians with the knowledge they need to control these bacteria.
Author: Hervé Tettelin
Publisher: Springer Nature
ISBN: 3030382818
Category : Science
Languages : en
Pages : 311
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Book Description
This open access book offers the first comprehensive account of the pan-genome concept and its manifold implications. The realization that the genetic repertoire of a biological species always encompasses more than the genome of each individual is one of the earliest examples of big data in biology that opened biology to the unbounded. The study of genetic variation observed within a species challenges existing views and has profound consequences for our understanding of the fundamental mechanisms underpinning bacterial biology and evolution. The underlying rationale extends well beyond the initial prokaryotic focus to all kingdoms of life and evolves into similar concepts for metagenomes, phenomes and epigenomes. The book’s respective chapters address a range of topics, from the serendipitous emergence of the pan-genome concept and its impacts on the fields of microbiology, vaccinology and antimicrobial resistance, to the study of microbial communities, bioinformatic applications and mathematical models that tie in with complex systems and economic theory. Given its scope, the book will appeal to a broad readership interested in population dynamics, evolutionary biology and genomics.
Author: Busi Siddhardha
Publisher: Springer Nature
ISBN: 9811516952
Category : Science
Languages : en
Pages : 685
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Book Description
This book provides essential insights into microbial pathogenesis, host-pathogen interactions, and the anti-microbial drug resistance of various human pathogens on the basis of various model organisms. The initial sections of the book introduce readers to the mechanisms of microbial pathogenesis, host-pathogen interactions, anti-microbial drug resistance, and the dynamics of biofilm formation. Due to the emergence of various microbial resistant strains, it is especially important to understand the prognosis for microbial infections, disease progression profiles, and mechanisms of resistance to antibiotic therapy in order to develop novel therapeutic strategies. In turn, the second part of the book presents a comparative analysis of various animal models to help readers understand microbial pathogenesis, host-pathogen interactions, anti-microbial drug discovery, anti-biofilm therapeutics, and treatment regimes. Given its scope, the book represents a valuable asset for microbiologists, biotechnologists, medical professionals, drug development researchers, and pharmacologists alike.
Author: World Health Organization
Publisher: World Health Organization
ISBN: 9789241550130
Category : Business & Economics
Languages : en
Pages : 0
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Book Description
WHO has launched new guidelines on use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antibiotics routinely to promote growth and prevent disease in healthy animals. These guidelines aim to help preserve the effectiveness of antibiotics that are important for human medicine by reducing their use in animals.
Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309131219
Category : Science
Languages : en
Pages : 330
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Book Description
Dr. Joshua Lederberg - scientist, Nobel laureate, visionary thinker, and friend of the Forum on Microbial Threats - died on February 2, 2008. It was in his honor that the Institute of Medicine's Forum on Microbial Threats convened a public workshop on May 20-21, 2008, to examine Dr. Lederberg's scientific and policy contributions to the marketplace of ideas in the life sciences, medicine, and public policy. The resulting workshop summary, Microbial Evolution and Co-Adaptation, demonstrates the extent to which conceptual and technological developments have, within a few short years, advanced our collective understanding of the microbiome, microbial genetics, microbial communities, and microbe-host-environment interactions.
Author: Jeffrey Griffiths
Publisher: Elsevier
ISBN: 012381507X
Category : Medical
Languages : en
Pages : 504
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Book Description
Emerging infectious diseases may be defined as diseases being caused by pathogens only recently recognized to exist. This group of diseases is important globally, and the experience of the last 30 years suggests that new emerging diseases are likely to bedevil us. As the global climate changes, so changes the environment, which can support not only the pathogens, but also their vectors of transmission. This expands the exposure and effects of infectious disease and, therefore, the importance of widespread understanding of the relationship between public health and infectious disease. Public Health and Infectious Diseases brings together chapters that explain reasons for the emergence of these infectious diseases. These include the ecological context of human interactions with other humans, with animals that may host human pathogens, and with a changing agricultural and industrial environment, increasing resistance to antimicrobials, the ubiquity of global travel, and international commerce. - Features the latest discoveries related to influenza with a newly published article by Davidson Hamer and Jean van Seventer - Provides a listing of rare diseases that have become resurgent or spread their geographic distribution and are re-emergent - Highlights dengue and malaria, as well as agents such as West Nile and other arboviruses that have spread to new continents causing widespread concerns - Includes discussions of climate influencing the spread of infectious disease and political and societal aspects
Author: Iqbal Ahmad
Publisher: Springer Nature
ISBN: 9811398712
Category : Medical
Languages : en
Pages : 680
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Book Description
This book compiles the latest information in the field of antibacterial discovery, especially with regard to the looming threat of multi-drug resistance. The respective chapters highlight the discovery of new antibacterial and anti-infective compounds derived from microbes, plants, and other natural sources. The potential applications of nanotechnology to the fields of antibacterial discovery and drug delivery are also discussed, and one section of the book is dedicated to the use of computational tools and metagenomics in antibiotic drug discovery. Techniques for efficient drug delivery are also covered. The book provides a comprehensive overview of the progress made in both antibacterial discovery and delivery, making it a valuable resource for academic researchers, as well as those working in the pharmaceutical industry.
Author: Eugénie Bergogne-Bérézin
Publisher: Springer
ISBN: 9781441926722
Category : Science
Languages : en
Pages : 0
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Book Description
There is currently increasing interest concerning the biology and disease caused by Acinetobacter species. Such interest, however, developed relatively slowly because of the necessity to clarify the confusing taxonomy of these organisms. Much work was needed to identify various species as members of this genus, to recognize their epidemiologic profile, their pathogenic role and their increasing importance as multi-antibiotic resistant organisms. In recent years improvement of genetic approaches, recognition of plasmids, integrons and chromosomal sources of resistance mechanisms aroused interest on the role of Acinetobacters in disease by many microbiologists and clinicians, especially internists and infectious disease specialists. In this regard, physicians are frequently confronted with extremely difficult therapeutic approaches for treatment and prevention of severe nosocomial infections due to multi antibiotic resistant Acinetobacter. Moreover, recent observations of community acquired infections have been reported, especially in patients with various risk factors such as immuno-deficiencies. Also, it is now becoming evident that Acinetobacter infections occur frequently in violent situations such as earthquake or war zones. The mechanisms of Acinetobacter virulence are becoming increasingly clear, providing new insights into their pathogenic role in community acquired infections. It is apparent the time is appropriate for detailed review of the increasing knowledge concerning important new information, both clinical and therapeutic, especially information concerning virulence, resistance mechanisms and typing of Acinetobacter spp. Many new findings are accumulating in almost an exponential manner since publication of previous books on this subject in 1991 and 1996.
