Resensitization to colistin results in rapid and stable recovery of adherence, serum resistance and ompW in Acinetobacter baumannii.

Autor: Boral J; Graduate School of Health Sciences, Koç University, Istanbul, Türkiye.; Koç University İşBank Center for Infectious Diseases (KUISCID), Koç University Hospital, Istanbul, Türkiye., Vatansever C; Koç University İşBank Center for Infectious Diseases (KUISCID), Koç University Hospital, Istanbul, Türkiye., Ozcan G; Graduate School of Health Sciences, Koç University, Istanbul, Türkiye.; Department of Medicine, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, Chicago, Illinois, United States of America., Keske S; Koç University İşBank Center for Infectious Diseases (KUISCID), Koç University Hospital, Istanbul, Türkiye., Menekse S; Department of Infectious Diseases, Koşuyolu Kartal Heart Training and Research Hospital, İstanbul, Türkiye., Gonen M; Koç University İşBank Center for Infectious Diseases (KUISCID), Koç University Hospital, Istanbul, Türkiye.; Department of Industrial Engineering, College of Engineering, Koç University, Istanbul, Türkiye., Can F; Graduate School of Health Sciences, Koç University, Istanbul, Türkiye.; Koç University İşBank Center for Infectious Diseases (KUISCID), Koç University Hospital, Istanbul, Türkiye.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Aug 28; Vol. 19 (8), pp. e0309307. Date of Electronic Publication: 2024 Aug 28 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0309307
Abstrakt: Background: Colistin resistance in Acinetobacter baumannii is an emerging problem that limits antimicrobial therapy options.
Materials & Methods: We isolated two pairs of colistin susceptible and colistin-resistant A. baumannii (K1007/K1006 and K408/K409) from two patients diagnosed with carbapenem-resistant A. baumannii infection. Colistin susceptible isolates were exposed to in vitro colistin induction for 50 generations. The selected cell populations were subjected to DNA and RNA sequencing and phenotypic assays.
Results: In the in vitro induction assay, K408 gained colistin resistance on the corresponding day of clinical resistance (K408-G25) and got resensitized to colistin in the consecutive generation (K408-G26). A significant upregulation of ompW, ata, adeFGH genes on K408-G25 was followed by a downregulation upon resensitization to colistin (G26). Despite the upregulation of the ompW gene in transcriptomic analysis, the ompW protein disappeared on K408-G25 and recovered in the resensitized generation (G26). In parallel, disrupted cell membrane integrity recovered in K408-G26. In the K408-G25, downregulation of pbpG and upregulation of pbp1a/pbp3 genes decreased serum-resistance which was reversed in the resensitized generation (G26). The K1007 did not gain colistin resistance amongst 50-generations, however, the generation corresponding to clinical resistance day (K1007-G9) had a similar trend with K408-G25. The clinical colistin-resistant K409 and K1006 had SNPs on pmrA and pmrB genes.
Conclusion: In this study, we observed that A. baumannii regulates adhesion, efflux pumps and serum-resistance associated genes as an early response to colistin stress. Besides, the ompW protein disappears in the cell membrane of colistin resistant cells which recovers after resensitization to colistin. The lack of ompW protein in colistin-resistant cells should be taken into consideration for escape mutants in development of antivirulence vaccination or treatment options.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Boral et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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