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      Pyomelanin biosynthetic pathway in pigment-producer strains from the pandemic Acinetobacter baumannii IC-5

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          Abstract

          BACKGROUND

          Acinetobacter baumannii outbreaks have been associated with pandemic International Clones (ICs), but the virulence factors involved with their pathogenicity are sparsely understood. Pigment production has been linked with bacterial pathogenicity, however, this phenotype is rarely observed in A. baumannii.

          OBJECTIVES

          This study aimed to characterise the reddish-brown pigment produced by A. baumannii strains, and to determine its biosynthetic pathway by genomic approaches.

          METHODS

          Pigment characterisation and antimicrobial susceptibility were conducted by phenotypic tests. The clonal relationship was obtained by pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The genome of an A. baumannii was obtained for characterisation of genes involved with pigment production.

          FINDINGS

          The pyomelanin was the pigment produced by A. baumannii. Strains were extensively drug resistant and belonged to the IC-5/ST79. The pyomelanin biosynthetic pathway was determined and presented a particular architecture concerning the peripheral ( tyrB, phhB and hpd) and central ( hmgB, hmgC and hmgR) metabolic pathway genes. The identification of a distant HmgA homologue, probably without dioxygenase activity, could explain pyomelanin production. Virulence determinants involved with adherence ( csuA/BABCDE and a T5bSS-carrying genomic island), and iron uptake ( basABCDEFGHIJ, bauABCDEF and barAB) were characterised.

          MAIN CONCLUSION

          There is a biosynthetic pathway compatible with the pyomelanin production observed in persistent A. baumannii IC-5 strains.

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          Most cited references33

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          Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance.

          Many different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided. © 2011 European Society of Clinical Microbiology and Infectious Diseases. No claim to original US government works.
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            Global evolution of multidrug-resistant Acinetobacter baumannii clonal lineages.

            The rapid expansion of Acinetobacter baumannii clinical isolates exhibiting resistance to carbapenems and most or all available antibiotics during the last decade is a worrying evolution. The apparent predominance of a few successful multidrug-resistant lineages worldwide underlines the importance of elucidating the mode of spread and the epidemiology of A. baumannii isolates in single hospitals, at a country-wide level and on a global scale. The evolutionary advantage of the dominant clonal lineages relies on the capability of the A. baumannii pangenome to incorporate resistance determinants. In particular, the simultaneous presence of divergent strains of the international clone II and their increasing prevalence in international hospitals further support the ongoing adaptation of this lineage to the hospital environment. Indeed, genomic and genetic studies have elucidated the role of mobile genetic elements in the transfer of antibiotic resistance genes and substantiate the rate of genetic alterations associated with acquisition in A. baumannii of various resistance genes, including OXA- and metallo-β-lactamase-type carbapenemase genes. The significance of single nucleotide polymorphisms and transposon mutagenesis in the evolution of A. baumannii has been also documented. Establishment of a network of reference laboratories in different countries would generate a more complete picture and a fuller understanding of the importance of high-risk A. baumannii clones in the international dissemination of antibiotic resistance. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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              Acinetobacter baumannii: human infections, factors contributing to pathogenesis and animal models.

              Acinetobacter baumannii has emerged as a medically important pathogen because of the increasing number of infections produced by this organism over the preceding three decades and the global spread of strains with resistance to multiple antibiotic classes. In spite of its clinical relevance, until recently, there have been few studies addressing the factors that contribute to the pathogenesis of this organism. The availability of complete genome sequences, molecular tools for manipulating the bacterial genome, and animal models of infection have begun to facilitate the identification of factors that play a role in A. baumannii persistence and infection. This review summarizes the characteristics of A. baumannii that contribute to its pathogenesis, with a focus on motility, adherence, biofilm formation, and iron acquisition. In addition, the virulence factors that have been identified to date, which include the outer membrane protein OmpA, phospholipases, membrane polysaccharide components, penicillin-binding proteins, and outer membrane vesicles, are discussed. Animal models systems that have been developed during the last 15 years for the study of A. baumannii infection are overviewed, and the recent use of these models to identify factors involved in virulence and pathogenesis is highlighted. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
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                Author and article information

                Journal
                Mem Inst Oswaldo Cruz
                Mem Inst Oswaldo Cruz
                mioc
                Memórias do Instituto Oswaldo Cruz
                Instituto Oswaldo Cruz, Ministério da Saúde
                0074-0276
                1678-8060
                06 November 2020
                2020
                : 115
                : e200371
                Affiliations
                [1 ]Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Genética Molecular de Microrganismos, Rio de Janeiro, RJ, Brasil
                [2 ]Universidade Federal de Roraima, Boa Vista, RR, Brasil
                Author notes
                + Corresponding author: ericafon@ 123456ioc.fiocruz.br

                EF - Conceptualisation and design of the study, performed the experiments, analyzed and interpreted the data, wrote, reviewed and edited the manuscript; RC - collected the bacterial strains; FF and SM - performed the experiments; ACV - conceptualisation and design of the study, scientific supervision, funding acquisition, revision, edition and final approve the manuscript. All authors have read and agreed to the published version of the manuscript. The authors declare no conflict of interest.

                Author information
                http://orcid.org/0000-0002-5029-7389
                Article
                00350
                10.1590/0074-02760200371
                7646211
                33174904
                a94d82bd-b776-4781-be92-3b95b3355b43

                This is an open-access article distributed under the terms of the Creative Commons Attribution License

                History
                : 13 July 2020
                : 16 October 2020
                Page count
                Figures: 2, Tables: 1, References: 30
                Categories
                Original Article

                international clone,pyomelanin pigment,adherence,extensively drug resistance,persistence

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