Transcriptome Remodeling of Acinetobacter baumannii during Infection and Treatment

Abstract

Acinetobacter baumannii is an increasingly common multidrug-resistant pathogen in health care settings. Although the genetic basis of antibiotic resistance mechanisms has been extensively studied, much less is known about how genetic variation contributes to other aspects of successful infections. Genetic changes that occur during host infection and treatment have the potential to remodel gene expression patterns related to resistance and pathogenesis. Longitudinal sets of multidrug-resistant A. baumannii isolates from eight patients were analyzed by RNA sequencing (RNA-seq) to identify differentially expressed genes and link them to genetic changes contributing to transcriptional variation at both within-patient and population levels. The number of differentially expressed genes among isolates from the same patient ranged from 26 (patient 588) to 145 (patient 475). Multiple patients had isolates with differential gene expression patterns related to mutations in the pmrAB and adeRS two-component regulatory system genes, as well as significant differences in genes related to antibiotic resistance, iron acquisition, amino acid metabolism, and surface-associated proteins. Population level analysis revealed 39 genetic regions with clade-specific differentially expressed genes, for which 19, 8, and 3 of these could be explained by insertion sequence mobilization, recombination-driven sequence variation, and intergenic mutations, respectively. Multiple types of mutations that arise during infection can significantly remodel the expression of genes that are known to be important in pathogenesis.

Colistin Heteroresistance and Involvement of the PmrAB Regulatory System in Acinetobacter baumannii

“…HR might be an alternative to the costly colistin resistance. Transcriptome remodeling during infection and treatment has been performed, and a convergent change was observed for clinical isolates with pmrAB mutations (28). Most isolates originated from patients treated with colistin.…”

Colistin heteroresistance and the involvement of the PmrAB regulatory system in Acinetobacter baumannii

“…Heteroresistance might be an alternative to the costly colistin resistance. A transcriptome remodelling has been portrayed during infection and treatment and a convergent change was observed for clinical isolates with pmrAB mutations (28). Most isolates originated from patients treated with colistin.…”

Expanding the paradigm for the outer membrane: Acinetobacter baumannii in the absence of endotoxin

“…Thus, these strains would be considered highly susceptible to the antibiotic and would lack lipid A modifications consistent with colistin resistance (> 2 µg ml −1 ). This makes it likely that host‐induced factors lead to active remodeling of the outer membrane and this phenotype was not stable in vitro (Wright et al ., ). That the expected phenotype was not detected in vitro suggests these mutations might be an artifact of next‐generation sequencing, and is consistent with similar findings in the Trent Lab (unpublished results, Trent Lab).…”