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      Acinetobacter baumannii biofilms: effects of physicochemical factors, virulence, antibiotic resistance determinants, gene regulation, and future antimicrobial treatments

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          Abstract

          Acinetobacter baumannii is a leading cause of nosocomial infections due to its increased antibiotic resistance and virulence. The ability of A. baumannii to form biofilms contributes to its survival in adverse environmental conditions including hospital environments and medical devices. A. baumannii has undoubtedly propelled the interest of biomedical researchers due to its broad range of associated infections especially in hospital intensive care units. The interplay among microbial physicochemistry, alterations in the phenotype and genotypic determinants, and the impact of existing ecological niche and the chemistry of antimicrobial agents has led to enhanced biofilm formation resulting in limited access of drugs to their specific targets. Understanding the triggers to biofilm formation is a step towards limiting and containing biofilm-associated infections and development of biofilm-specific countermeasures. The present review therefore focused on explaining the impact of environmental factors, antimicrobial resistance, gene alteration and regulation, and the prevailing microbial ecology in A. baumannii biofilm formation and gives insights into prospective anti-infective treatments.

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          Uncovering the mechanisms of Acinetobacter baumannii virulence

          Acinetobacter baumannii is a nosocomial pathogen that causes ventilator-associated as well as bloodstream infections in critically ill patients, and the spread of multidrug-resistant Acinetobacter strains is cause for concern. Much of the success of A. baumannii can be directly attributed to its plastic genome, which rapidly mutates when faced with adversity and stress. However, fundamental virulence mechanisms beyond canonical drug resistance were recently uncovered that enable A. baumannii and, to a limited extent, other medically relevant Acinetobacter species to successfully thrive in the health-care environment. In this Review, we explore the molecular features that promote environmental persistence, including desiccation resistance, biofilm formation and motility, and we discuss the most recently identified virulence factors, such as secretion systems, surface glycoconjugates and micronutrient acquisition systems that collectively enable these pathogens to successfully infect their hosts.
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            Mechanisms of biofilm resistance to antimicrobial agents.

            Biofilms are communities of microorganisms attached to a surface. It has become clear that biofilm-grown cells express properties distinct from planktonic cells, one of which is an increased resistance to antimicrobial agents. Recent work has indicated that slow growth and/or induction of an rpoS-mediated stress response could contribute to biocide resistance. The physical and/or chemical structure of exopolysaccharides or other aspects of biofilm architecture could also confer resistance by exclusion of biocides from the bacterial community. Finally, biofilm-grown bacteria might develop a biofilm-specific biocide-resistant phenotype. Owing to the heterogeneous nature of the biofilm, it is likely that there are multiple resistance mechanisms at work within a single community. Recent research has begun to shed light on how and why surface-attached microbial communities develop resistance to antimicrobial agents.
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              Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

              Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.
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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                Infection and Drug Resistance
                Infection and Drug Resistance
                Dove Medical Press
                1178-6973
                2018
                15 November 2018
                : 11
                : 2277-2299
                Affiliations
                [1 ]Virology and Microbiology Research Group, School of Health Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa, elzowalatym@ 123456ukzn.ac.za
                [2 ]Discipline of Microbiology, School of Life Sciences, College of Agriculture, Engineering and Sciences, University of KwaZulu-Natal, Durban, South Africa
                Author notes
                Correspondence: Mohamed E El Zowalaty, Virology and Microbiology Research Group, School of Health Sciences, Blok F2 Office 517, Westville campus, University Road, Private Bag X54004, Durban 4000, South Africa, Tel +27 31 260 7891, Fax +27 31 260 7872, Email elzowalatym@ 123456ukzn.ac.za
                Article
                idr-11-2277
                10.2147/IDR.S169894
                6245380
                30532562
                6fbb0901-b48d-4ad0-9ea4-5ef47331ace6
                © 2018 Eze et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Categories
                Review

                Infectious disease & Microbiology
                acinetobacter baumannii,biofilm,physicochemical,antibiotics,resistance,in vivo model,virulence,treatment

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