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Valcek, A.

Publications and source records attributed to Valcek, A..

3 recordsLinked to original sources

Acinetobase: the comprehensive database and repository of Acinetobacter strains.

BackgroundAcinetobacter baumannii is one of the most problematic nosocomial pathogens that can efficiently thrive within hospital settings, mainly due to resistances towards antibiotics, desiccation, disinfectants, human serum and oxidative stress. Recently, increased resistance against last resort antibiotics earns this bacterium the highest priority concern classified by the CDC and the WHO. An obvious hallmark of this bacterium is the high heterogeneity observed amongst A. baumannii isolates, with a limited core genome. This feature complexifies the study of A. baumannii bacteria as an entity, subsequently reflected in a diversity of phenotypes of not only antimicrobial and environmental resistance but also virulence. Main bodyHigh degree of genome plasticity, along with the use of a limited subset of established reference strains, can lead to strain-specific observations, decreasing the global understanding of this pathogenic agent. Phenotypic variability of A. baumannii strains is easily observable such as with the macrocolony morphologies, in vitro and in vivo virulence, natural competence level, production of different capsular polysaccharide structures and cellular densities. Some strains encode an extensive amount of virulence factors while other, including the reference strains, lack several key ones. The lack/excess of genes or specific physiological processes might interfere with in vivo and in vitro experiments, thus providing limited impact on the global understanding of Acinetobacter bacteria as a whole. ConclusionAs an answer to the high heterogeneity amongst A. baumannii strains, we propose a first comprehensive database that includes the bacterial strains and the associated phenotypic and genetic data. This new repository, freely accessible to the entire scientific community, allow selecting the best bacterial isolate(s) related to any biological question, using an efficient and fast exchange platform.

bioinformatics↗

What are the reference strains of Acinetobacter baumannii referring to?

We assembled the whole genome sequence (WGS) of a collection of 43 non-redundant modern clinical isolates and four broadly used reference strains of Acinetobacter baumannii. Comparison of these isolates and their WGS confirmed the high heterogeneity in capsule loci, sequence types, the presence of virulence and antibiotic resistance genes. However, a significant portion of clinical isolates strongly differ when compared to several reference strains in the light of colony morphology, cellular density, capsule production, natural transformability and in vivo virulence. These genetic and phenotypic differences between current circulating strains of A. baumannii and established reference strains could hamper the study of A. baumannii as an entity. The broadly used reference strains led to the current state of the art of the A. baumannii field, however, we propose that established reference strains in the A. baumannii field should be carefully used, because of the high genetic and phenotypic heterogeneities. In this study, we generated a collection of high-quality nucleotide sequences of 43 modern clinical isolates with the corresponding multi-level phenotypic characterizations. Beside the contribution of novel fundamental observations generated in this study, the phenotypic and genetic data, along with the bacterial strains themselves, will be further accessible using the first open access online platform called "Acinetobase". Therefore, a rational choice of modern strains will be possible to select the ones that suit the needs of specific biological questions.

microbiology↗

Antimicrobial activity of a repurposed harmine-derived compound on extensively drug-resistant Acinetobacter baumannii clinical isolates

SynopsisO_ST_ABSObjectivesC_ST_ABSThe spread of antibiotic resistant bacteria is an important threat for human healthcare. Acinetobacter baumannii bacteria impose one of the major issues, as multidrug- to pandrug-resistant strains have been found, rendering some infections untreatable. In addition, A. baumannii is a champion in surviving in harsh environments, being capable of resisting to disinfectants and to persist prolonged periods of desiccation. Due to the high degree of variability found in A. baumannii isolates, the search for new antibacterials is challenging. Here, we screened a compound library to identify compounds active against recent isolates of A. baumannii bacteria. MethodsA repurposing drug screen was undertaken to identify A. baumannii growth inhibitors. One hit was further characterized by determining its IC50 and testing its activity on 43 recent clinical A. baumannii isolates, amongst which 40 are extensively drug- and carbapenem-resistant strains. ResultsThe repurposing screen led to the identification of a harmine-derived compound, called HDC1, which proved to have bactericidal activity on the multidrug-resistant AB5075-VUB reference strain with an IC50 of 48.23 {micro}M. In addition, HDC1 impairs growth of all 43 recent clinical A. baumannii isolates. ConclusionsWe identified a compound with inhibitory activity on all tested, extensively drug-resistant clinical A. baumannii isolates.

microbiology↗