Genome dynamics of multidrug-resistant Acinetobacter baumannii during infection and treatment

Abstract

BackgroundLimited treatment options are available for patients infected with multidrug (MDR)- or pan-drug (PDR)-resistant bacterial pathogens, resulting in infections that can persist for weeks or months. In order to better understand transmission and evolutionary dynamics of MDR Acinetobacter baumannii (Ab) during long-term infection, we analyzed genomes from a series of isolates from individual patients at isolate-specific, patient-specific, and population levels.MethodsWhole genome analysis of longitudinal isolates (range 2-10 isolates per patient spanning 0-829 days) from 40 patients included detection of single-nucleotide variants (SNVs), insertion sequence (IS) mapping, and gene content changes.ResultsPhylogenetic analysis revealed that a significant fraction of apparently persistent infections are in fact due to re-infection with new strains. SNVs primarily resulted in protein coding changes, and IS events primarily interrupted genes or were in an orientation such that the adjacent gene would be over-expressed. Mutations acquired during infection were over-represented in transcriptional regulators, notably pmrAB and adeRS, which can mediate resistance to the last line therapies colistin and tigecycline, respectively, as well as transporters, surface structures, and iron acquisition genes.ConclusionsMost SNVs and IS events were isolate-specific indicating these mutations did not become fixed on the time scale investigated, yet over-representation of independent mutations in some genes or functional categories suggests that they are under selective pressure. Genome analysis at the population-level suggests that gene transfer including recombination also contributes to Ab evolutionary dynamics. These findings provide important insight into the transmission dynamics of Ab and the identification of patients with repeat infections has implications for infection control programs targeted to this pathogen.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0279-y) contains supplementary material, which is available to authorized users.

A Light-Regulated Type I Pilus Contributes to Acinetobacter baumannii Biofilm, Motility, and Virulence Functions

“…Overall, these observations indicate that the 17978 PrpABCD system and its MAR002 LH92_11070-LH92_11085 homolog play a role in the physiology and virulence of A. baumannii. However, some of the biological roles associated with these pilus assembly systems, such as adherence and biofilm biogenesis, seem to be strain specific, a phenomenon that has been described for other A. baumannii traits, including the different effects of mutations in genes coding for the same antimicrobial resistance functions in different clinical isolates (36)(37)(38). Furthermore, it is important to note that A. baumannii MAR002 was classified as an ST271 genotype isolate that is not related to any of the high-biofilm producers reported and does not map to any international clonal lineage (29).…”

A large conjugative Acinetobacter baumannii plasmid carrying the sul2 sulphonamide and strAB streptomycin resistance genes

“…baumannii, resistance genes are often located in the chromosome in genomic resistance islands (Blackwell et al, 2016;Chan et al, 2015;Holt et al, 2016;Nigro and Hall, 2016;Wright et al, 2016). However, recent reports indicate the significance of A. baumannii plasmids as vehicles to introduce antibiotic resistance genes such as oxa23 and bla NDM leading to resistance to the front line carbapenem antibiotics (Hamidian et al, 2014a;Hamidian et al, 2014b;Jones et al, 2014;Nigro and Hall, 2016;Nigro et al, 2015).…”

Tracking Cefoperazone/Sulbactam Resistance Development In vivo in A. baumannii Isolated from a Patient with Hospital-Acquired Pneumonia by Whole-Genome Sequencing

“…It has been seen as a basis for whole-genome sequencing revealing the mechanism of bacterial pathogen resistance that develops in patients ( Snitkin et al, 2011 ; Wright et al, 2014 ; Holt et al, 2015 ). Wright et al (2016) sequenced 136 strains of A. baumannii isolated from patients and showed the genome changes occurred mainly due to the single nucleotide variance in protein coding regions and IS element. Genome sequenced A. baumannii showed the colistin resistance was due to the mutations in transcriptional regulatory genes ( Cheah et al, 2016 ).…”