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Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361751


Species of Mycobacteriaceae cause disease in animals and humans, including tuberculosis and leprosy. Individuals infected with organisms in the Mycobacterium tuberculosis complex (MTBC) or non-tuberculous mycobacteria (NTM) may present identical symptoms, however the treatment for each can be different. Although the NTM infection is considered less vital due to the chronicity of the disease and the infrequency of occurrence in healthy populations, diagnosis and differentiation among Mycobacterium species currently require culture isolation, which can take several weeks. The use of volatile organic compounds (VOCs) is a promising approach for species identification and in recent years has shown promise for use in the rapid analysis of both in vitro cultures as well as ex vivo diagnosis using breath or sputum. The aim of this contribution is to analyze VOCs in the culture headspace of seven different species of mycobacteria and to define the volatilome profiles that are discriminant for each species. For the pre-concentration of VOCs, solid-phase micro-extraction (SPME) was employed and samples were subsequently analyzed using gas chromatography-quadrupole mass spectrometry (GC-qMS). A machine learning approach was applied for the selection of the 13 discriminatory features, which might represent clinically translatable bacterial biomarkers.

Metaboloma , Mycobacterium abscessus/química , Complexo Mycobacterium avium/química , Mycobacterium avium/química , Mycobacterium bovis/química , Mycobacterium/química , Compostos Orgânicos Voláteis/isolamento & purificação , Biomarcadores/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Aprendizado de Máquina/estatística & dados numéricos , Mycobacterium/metabolismo , Mycobacterium abscessus/metabolismo , Mycobacterium avium/metabolismo , Complexo Mycobacterium avium/metabolismo , Mycobacterium bovis/metabolismo , Análise de Componente Principal , Microextração em Fase Sólida , Compostos Orgânicos Voláteis/classificação , Compostos Orgânicos Voláteis/metabolismo
Mol Microbiol ; 21(2): 321-9, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8858587


Mycobacterium avium is an intracellular pathogen and a major opportunistic infectious agent observed in patients with acquired immune deficiency syndrome (AIDS). Evidence suggests that the initial portal of infection by M. avium is often the gastrointestinal tract. However, the mechanism by which the M. avium crosses the epithelial barrier is unclear. A possible mechanism is suggested by the ability of M. avium to bind fibronectin, an extracellular matrix protein that is a virulence factor for several extracellular pathogenic bacteria which bind to mucosal surfaces. To further characterize fibronectin binding by M. avium, we have cloned the M. avium fibronectin-attachment protein (FAP). The M. avium FAP (FAP-A) has an unusually large number of Pro and Ala residues (40% overall) and is 50% identical to FAP of both Mycobacterium leprae and Mycobacterium tuberculosis. Using recombinant FAP-A and FAP-A peptides, we show that two non-continuous regions in FAP-A bind fibronectin. Peptides from these regions and homologous sequences from M. leprae FAP inhibit fibronectin binding by both M. avium and Mycobacterium bovis Bacillus Calmette-Guerin (BCG). These regions have no homology to eukaryotic fibronectin-binding proteins and are only distantly related to fibronectin-binding peptides of Gram-positive bacteria. Nevertheless, these fibronectin-binding regions are highly conserved among the mycobacterial FAPs, suggesting an essential function for this interaction in mycobacteria infection of their metazoan hosts.

Fibronectinas/metabolismo , Complexo Mycobacterium avium/genética , Complexo Mycobacterium avium/metabolismo , Mycobacterium/genética , Mycobacterium/metabolismo , Oligopeptídeos/genética , Oligopeptídeos/metabolismo , Infecções Oportunistas Relacionadas com a AIDS/etiologia , Sequência de Aminoácidos , Sítios de Ligação/genética , Clonagem Molecular , Sequência Conservada , Humanos , Dados de Sequência Molecular , Complexo Mycobacterium avium/patogenicidade , Infecção por Mycobacterium avium-intracellulare/etiologia , Mycobacterium bovis/metabolismo , Ligação Proteica , Homologia de Sequência de Aminoácidos , Especificidade da Espécie
Acta Leprol ; 7 Suppl 1: 195-9, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2503989


Synergistic effects of combinations of anti-mycobacterial drugs on Mycobacterium avium complex (MAC) in vitro was studied by radiometric respirometry. Pronounced synergy was seen for several drug combinations where ethambutol was found to be the key drug in the synergistic potentiation. Microcalorimetric studies show that a very rapid physico-chemical interaction occurs between the cell-surface of MAC and ethambutol. When MAC cells were pretreated with ethambutol and then subjected to streptomycin the thermal response significantly differed from that seen with MAC cells which had not been pretreated. The typical thermal effects of the interaction of ethambutol with live and UV-killed MAC cells was not seen with heat-killed MAC cells. It is proposed that specific cell-surface protein(s) act as receptors in the initial interaction with ethambutol.

Antibacterianos/administração & dosagem , Etambutol/administração & dosagem , Complexo Mycobacterium avium/efeitos dos fármacos , Calorimetria , Sinergismo Farmacológico , Temperatura Alta , Complexo Mycobacterium avium/metabolismo , Radiometria , Receptores de Droga/metabolismo , Estreptomicina/administração & dosagem