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Colistin Dependence in Extensively Drug-Resistant Acinetobacter baumannii Strain Is Associated with ISAjo2 and ISAba13 Insertions and Multiple Cellular Responses.
Chamoun, Sherley; Welander, Jenny; Martis-Thiele, Mihaela-Maria; Ntzouni, Maria; Claesson, Carina; Vikström, Elena; Turkina, Maria V.
Afiliación
  • Chamoun S; Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
  • Welander J; Department of Biomedical and Clinical Sciences, Linköping University and Department of Clinical Microbiology, University Hospital, SE-58185 Linköping, Sweden.
  • Martis-Thiele MM; Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
  • Ntzouni M; National Bioinformatics Infrastructure Sweden, Bioinformatics Platform, Science for Life Laboratory, SE17165 Solna, Sweden.
  • Claesson C; Core Facility, Faculty of Medicine and Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
  • Vikström E; Department of Biomedical and Clinical Sciences, Linköping University and Department of Clinical Microbiology, University Hospital, SE-58185 Linköping, Sweden.
  • Turkina MV; Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33430070
ABSTRACT
The nosocomial opportunistic Gram-negative bacterial pathogen Acinetobacter baumannii is resistant to multiple antimicrobial agents and an emerging global health problem. The polymyxin antibiotic colistin, targeting the negatively charged lipid A component of the lipopolysaccharide on the bacterial cell surface, is often considered as the last-resort treatment, but resistance to colistin is unfortunately increasing worldwide. Notably, colistin-susceptible A. baumannii can also develop a colistin dependence after exposure to this drug in vitro. Colistin dependence might represent a stepping stone to resistance also in vivo. However, the mechanisms are far from clear. To address this issue, we combined proteogenomics, high-resolution microscopy, and lipid profiling to characterize and compare A. baumannii colistin-susceptible clinical isolate (Ab-S) of to its colistin-dependent subpopulation (Ab-D) obtained after subsequent passages in moderate colistin concentrations. Incidentally, in the colistin-dependent subpopulation the lpxA gene was disrupted by insertion of ISAjo2, the lipid A biosynthesis terminated, and Ab-D cells displayed a lipooligosaccharide (LOS)-deficient phenotype. Moreover, both mlaD and pldA genes were perturbed by insertions of ISAjo2 and ISAba13, and LOS-deficient bacteria displayed a capsule with decreased thickness as well as other surface imperfections. The major changes in relative protein abundance levels were detected in type 6 secretion system (T6SS) components, the resistance-nodulation-division (RND)-type efflux pumps, and in proteins involved in maintenance of outer membrane asymmetry. These findings suggest that colistin dependence in A. baumannii involves an ensemble of mechanisms seen in resistance development and accompanied by complex cellular events related to insertional sequences (ISs)-triggered LOS-deficiency. To our knowledge, this is the first study demonstrating the involvement of ISAjo2 and ISAba13 IS elements in the modulation of the lipid A biosynthesis and associated development of dependence on colistin.
Texto completo: Disponible Colección: Bases de datos internacionales Contexto en salud: ODS3 - Salud y Bienestar Tema en salud: Meta 3.8: Alcanzar cobertura universal de salud Base de datos: MEDLINE Tipo de estudio: Factores de riesgo Idioma: Inglés Año: 2021 Tipo del documento: Artículo País de afiliación: Suecia

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Texto completo: Disponible Colección: Bases de datos internacionales Contexto en salud: ODS3 - Salud y Bienestar Tema en salud: Meta 3.8: Alcanzar cobertura universal de salud Base de datos: MEDLINE Tipo de estudio: Factores de riesgo Idioma: Inglés Año: 2021 Tipo del documento: Artículo País de afiliación: Suecia