Longitudinal genomics reveals carbapenem-resistant Acinetobacter baumannii population changes with emergence of highly resistant ST164 clone

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a persistent nosocomial pathogen that poses a significant threat to global public health, particularly in intensive care units (ICUs). Here we report a three-month longitudinal genomic surveillance study conducted in a Hangzhou ICU in 2021. This followed a three-month study conducted in the same ICU in 2019, and infection prevention and control (IPC) interventions targeting patients, staff and the ICU environment. Most A. baumannii isolated in this ICU in 2021 were CRAB (80.9%; 419/518) with higher-level resistance to carbapenems. This was accompanied by the proportion of global clone 2 (GC2) isolates falling from 99.5% in 2019 to 50.8% (213/419) in 2021. The phylogenetic diversity of GC2 increased, apparently driven by regular introductions of distinct clusters in association with patients. The remaining CRAB (40.2%; 206/419) were a highly clonal population of ST164. Isolates of ST164 carried bla_NDM-1 and bla_OXA-23 carbapenemase genes, and exhibited higher carbapenem MIC₅₀/MIC₉₀ values than GC2. Comparative analysis of publicly available genomes from 26 countries (five continents) revealed that ST164 has evolved towards carbapenem resistance on multiple independent occasions. Its success in this ICU and global capacity for acquiring resistance determinants indicate that ST164 CRAB is an emerging high-risk lineage of global concern.

Fig. 1. The ICU A. baumannii population.

A The upper panel shows the CRAB clone change model with their isolation rate in the ICU (Created in BioRender. Chen, Y. (2024) BioRender.com/q30i340). The below panel diaplays the comparison of the A. baumannii populations collected in this ICU over the initial (2019) and follow-up (2021) study periods. Horizontal bars are proportional to the number of isolates of given sequence types (STs), which are labelled and represented by different colours. Thinner horizontal lines and labels indicate whether isolates were carbapenem-resistant (CRAB; red) or carbapenem-sensitive (CSAB; blue). B Overview of the spatiotemporal distribution of GC2/ST2 (blue) and ST164 (orange) isolates over the course of the 2021 study. Bed unit and room numbers are indicated on the horizontal axis, and study week numbers are on the vertical axis. The sizes of the circles correspond to the number of isolates collected from each patient/bed unit at each sampling timepoint. Source data are provided as a Source Data file.

Fig. 2. The ICU GC2 population observed in this study.

A Core-gene phylogeny (left) and cluster characteristics (right). Reference genomes for clusters obtained in the 2019 study are indicated by coloured circles at branch tips. Cluster designations from this study are indicated by coloured boxes to the right of the phylogeny, along with boxes shaded as outlined in the key to the left of the Figure. The phylogeny featured three large clusters were labelled as x, y and z. B Temporal distribution of GC2 clusters over the course of this study. For each study week, columns are divided according to the number of isolates of each GC2 cluster that were obtained, with colours corresponding to the key in part A. C Spatiotemporal distribution of transient GC2 clusters introduced by patients over the course of this study. The meaning of shapes is outlined in the key below, and colours correspond to those in the key in part A. Source data are provided as a Source Data file.

Fig. 3. Genomic characteristics of ST164 A. baumannii.

A Schematic overview of the genome of ST164 isolates DETAB-P462. The chromosome is shown as a large circle with the locations of antibiotic resistance genes, MLST alleles, capsule (K) and outer core (OC) loci indicated. To the right, plasmids pDETAB17-21 and their sizes are shown (not to scale). B Time-dated phylogeny of the ST164 population examined in this study. Prominent branch dates are labelled, and the colours to the right of the phylogeny reflect ST164 clusters or the presence of antibiotic-resistance genes and plasmids as outlined in the key. SNP distances between the four ST164 clusters are indicated in circles filled in various colours. The blue arrow indicates the position of DETAB-R21, the reference isolated that was isolated in this ICU in early 2021. Source data are provided as a Source Data file.

Fig. 4. Distribution of ST164 in this ICU.

A Temporal distribution of ST164 clusters over the course of this study. For each study week, columns are divided according to the number of isolates of each ST164 cluster that were obtained, with colours corresponding to the key. Spatiotemporal distribution of ST164 clusters isolated from patients (B) and the ICU environment (C). Colours correspond to the key in part A, and the sizes of bubbles to the numbers of isolates indicated by the key in part B. Source data are provided as a Source Data file.

Fig. 5. Global ST164 population structure and distribution.

A A tree of 131 global ST164 strains and 4 representative isolates collected from our ICU was built and further visualised using iTOL v5. The information of ST_Oxford, location, continent, host and cabapenemases distribution was shown. Clades 1–7 were labelled as different colours. The reference strain DETAB-R21 was labelled as a blue name. Four representative strains from this study were indicated with red names. B Temporal distribution of strain numbers and carbapenemase genes. C Geographical distribution of major ST164 strains in the world and characteristics of carbapenemase carried by the strains. OXA-23, OXA-420, OXA-23+OXA-58, OXA-23+NDM-1, NDM-1 and none were shown as various colours. The black circle with three arrows means that ST164 CRAB may be widely spread in Asia. The map file was downloaded from ChiPlot v1 (https://www.chiplot.online/). Source data are provided as a Source Data file.