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      Rapid in vitro differentiation of bacteria by ion mobility spectrometry

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          Abstract

          Rapid screening of infected people plays a crucial role in interrupting infection chains. However, the current methods for identification of bacteria are very tedious and labor intense. Fast on-site screening for pathogens based on volatile organic compounds (VOCs) by ion mobility spectrometry (IMS) could help to differentiate between healthy and potentially infected subjects. As a first step towards this, the feasibility of differentiating between seven different bacteria including resistant strains was assessed using IMS coupled to multicapillary columns (MCC-IMS). The headspace above bacterial cultures was directly drawn and analyzed by MCC-IMS after 90 min of incubation. A cluster analysis software and statistical methods were applied to select discriminative VOC clusters. As a result, 63 VOC clusters were identified, enabling the differentiation between all investigated bacterial strains using canonical discriminant analysis. These 63 clusters were reduced to 7 discriminative VOC clusters by constructing a hierarchical classification tree. Using this tree, all bacteria including resistant strains could be classified with an AUC of 1.0 by receiver-operating characteristic analysis. In conclusion, MCC-IMS is able to differentiate the tested bacterial species, even the non-resistant and their corresponding resistant strains, based on VOC patterns after 90 min of cultivation. Although this result is very promising, in vivo studies need to be performed to investigate if this technology is able to also classify clinical samples. With a short analysis time of 5 min, MCC-IMS is quite attractive for a rapid screening for possible infections in various locations from hospitals to airports.

          Key Points

          • Differentiation of bacteria by MCC-IMS is shown after 90-min cultivation.

          • Non-resistant and resistant strains can be distinguished.

          • Classification of bacteria is possible based on metabolic features.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00253-021-11315-w.

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          Most cited references35

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          Spread of a novel influenza A (H1N1) virus via global airline transportation.

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            The scent of disease: volatile organic compounds of the human body related to disease and disorder.

            Hundreds of volatile organic compounds (VOCs) are emitted from the human body, and the components of VOCs usually reflect the metabolic condition of an individual. Therefore, contracting an infectious or metabolic disease often results in a change in body odour. Recent progresses in analytical techniques allow rapid analyses of VOCs derived from breath, blood, skin and urine. Disease-specific VOCs can be used as diagnostic olfactory biomarkers of infectious diseases, metabolic diseases, genetic disorders and other kinds of diseases. Elucidation of pathophysiological mechanisms underlying production of disease-specific VOCs may provide novel insights into therapeutic approaches for treatments for various diseases. This review summarizes the current knowledge on chemical and clinical aspects of body-derived VOCs, and provides a brief outlook at the future of olfactory diagnosis.
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              Mechanisms of Methicillin Resistance in Staphylococcus aureus.

              Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usually conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), with significantly lower affinity for β-lactams. This resistance allows cell-wall biosynthesis, the target of β-lactams, to continue even in the presence of typically inhibitory concentrations of antibiotic. PBP2a is encoded by the mecA gene, which is carried on a distinct mobile genetic element (SCCmec), the expression of which is controlled through a proteolytic signal transduction pathway comprising a sensor protein (MecR1) and a repressor (MecI). Many of the molecular and biochemical mechanisms underlying methicillin resistance in S. aureus have been elucidated, including regulatory events and the structure of key proteins. Here we review recent advances in this area.
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                Author and article information

                Contributors
                jessy.schoenfelder@izi.fraunhofer.de
                Journal
                Appl Microbiol Biotechnol
                Appl Microbiol Biotechnol
                Applied Microbiology and Biotechnology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0175-7598
                1432-0614
                11 May 2021
                11 May 2021
                2021
                : 105
                : 10
                : 4297-4307
                Affiliations
                [1 ]GRID grid.418008.5, ISNI 0000 0004 0494 3022, MicroDiagnostics, , Fraunhofer Institute for Cell Therapy and Immunology IZI, ; Leipzig, Germany
                [2 ]GRID grid.11348.3f, ISNI 0000 0001 0942 1117, Institute for Biochemistry and Biology, , University of Potsdam, ; Potsdam, Germany
                [3 ]Project Hub Microelectronic and Optical Systems for Biomedicine MEOS, Fraunhofer Institute for Cell Therapy and Immunology IZI, Erfurt, Germany
                Article
                11315
                10.1007/s00253-021-11315-w
                8140968
                33974116
                ca66ba48-47bc-4efb-b603-cba3a8ea0529
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 October 2020
                : 8 April 2021
                : 20 April 2021
                Funding
                Funded by: BMBF
                Award ID: 03ZZ0812B
                Categories
                Methods and Protocols
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2021

                Biotechnology
                bacteria identification,volatile organic compounds (voc),ion mobility spectrometry (ims),antibiotic resistance,infection,diagnostic

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