Analysis of tigecycline resistance development in clinical Acinetobacter baumannii isolates through a combined genomic and transcriptomic approach

Abstract

Tigecycline (Tgc) is considered a last-resort antibiotic for the treatment of multi-drug resistant bacteria. To study Tgc resistance development in the important nosocomial pathogen Acinetobacter baumannii, we adopted six clinical isolates from three patients undergoing antibiotic treatment, and bacterial genomic sequences and seven strand-specific transcriptomes were studied. Interestingly, the Tgc-intermediate 2015ZJAB1 only differed from Tgc-resistant 2015ZJAB2 in an SNP-clustered region including OprD, a sugar-type MFS permease, and a LuxR-type transcriptional regulator. Surprisingly, an almost identical region was found in 2015ZJAB3, which supports the possibility of a homologous recombination event that increased Tgc resistance. Furthermore, comparative transcriptomic analysis identified significantly regulated genes associated with Tgc resistance, which was verified using qRT-PCR. Three enriched COG categories included amino acid transport and metabolism, transcription, and inorganic ion transport and metabolism. KEGG analysis revealed common features under Tgc conditions, including up regulated benzoate degradation and a less active TCA cycle. This may be related to selective antimicrobial pressure in the environment and adaptation by lowering metabolism. This study provides the first report of an in vivo evolutionary process that included a putative homologous recombination event conferring Tgc resistance in clinical A. baumannii isolates in which transcriptome analysis revealed resistance-conferring genes and related metabolism characteristics.

Integrative analysis of outer membrane vesicles proteomics and whole-cell transcriptome analysis of eravacycline induced Acinetobacter baumannii strains

“…It was reported by Vrentas et al, that the downregulation of RNA synthesis occurs as a result of protein synthesis inhibition [34]. In the present study, the transfer RNAs were downregulated in both the ATCC 19606 and JU0126 strain, which explains the adaptation of the bacterium to pressure, trying to keep the metabolic process minimal, similar reports on the reduced metabolism due to tigecycline induction was done by Liu et al [35].…”

Isolation and Whole-genome Sequence Analysis of the Imipenem Heteroresistant Acinetobacter baumannii Clinical Isolate HRAB-85

“…Approximately 72% of the genes were assigned to a COG functional category ( Supplementary Fig. S2), of which the largest group was "general function prediction only"(R), followed by the classes of genes involved in amino acid transport and metabolism (E), transcription (K), translation, ribosomal structure and biogenesis (J), and lipid transport and metabolism (I).This result was basically consistent with a previous functional analysis of the COG classification for multidrug-resistant (MDR) A. baumanni (Liu et al, 2016).…”

Integrative analysis of outer membrane vesicles proteomics and whole-cell transcriptome analysis of eravacycline induced Acinetobacter baumannii strains

“…It was reported by Vrentas et al, that the downregulation of RNA synthesis occurs as a result of protein synthesis inhibition [35]. In the present study, the transfer RNAs were downregulated in both the ATCC 19606 and JU0126 strain, which explains the adaptation of the bacterium to pressure, trying to keep the metabolic process minimal, similar reports on the reduced metabolism due to tigecycline induction was done by Liu et al [36].…”