Evolution of a pathogen: a comparative genomics analysis identifies a genetic pathway to pathogenesis in Acinetobacter

Abstract

Acinetobacter baumannii is an emergent and global nosocomial pathogen. In addition to A. baumannii, other Acinetobacter species, especially those in the Acinetobacter calcoaceticus-baumannii (Acb) complex, have also been associated with serious human infection. Although mechanisms of attachment, persistence on abiotic surfaces, and pathogenesis in A. baumannii have been identified, the genetic mechanisms that explain the emergence of A. baumannii as the most widespread and virulent Acinetobacter species are not fully understood. Recent whole genome sequencing has provided insight into the phylogenetic structure of the genus Acinetobacter. However, a global comparison of genomic features between Acinetobacter spp. has not been described in the literature. In this study, 136 Acinetobacter genomes, including 67 sequenced in this study, were compared to identify the acquisition and loss of genes in the expansion of the Acinetobacter genus. A whole genome phylogeny confirmed that A. baumannii is a monophyletic clade and that the larger Acb complex is also a well-supported monophyletic group. The whole genome phylogeny provided the framework for a global genomic comparison based on a blast score ratio (BSR) analysis. The BSR analysis demonstrated that specific genes have been both lost and acquired in the evolution of A. baumannii. In addition, several genes associated with A. baumannii pathogenesis were found to be more conserved in the Acb complex, and especially in A. baumannii, than in other Acinetobacter genomes; until recently, a global analysis of the distribution and conservation of virulence factors across the genus was not possible. The results demonstrate that the acquisition of specific virulence factors has likely contributed to the widespread persistence and virulence of A. baumannii. The identification of novel features associated with transcriptional regulation and acquired by clades in the Acb complex presents targets for better understanding the evolution of pathogenesis and virulence in the expansion of the genus.

Figure 1. A whole genome phylogeny of 136 sequenced genomes in the genus Acinetobacter.

The phylogeny was inferred with FastTree2 on a single nucleotide polymorphism (SNP) matrix alignment calculated with kSNP and filtered with noisy . The phylogeny was rooted with A. radioresistens. Genomes sequenced in the current study are shown in red. Genomes in the Acinetobacter calcoaceticus-baumannii (Acb) complex are colored by clade.

Figure 2. A heatmap of blast score ratio (BSR) values for branch specific regions in the Acb complex.

BSR values were visualized with the multi-experiment viewer . Samples were clustered using an average linkage clustering algorithm. Numbers for each feature correlate with features described in Table 1. Raw data values are shown in Table S5.

Figure 3. A heatmap of blast score ratio (BSR) values for iron acquisition genes in Acinetobacter.

BSR values were visualized with the multi-experiment viewer . Accession details for each gene in specific iron acquisition systems are shown in Table S3, with raw data shown in Table S5.

Figure 4. A heatmap of blast score ratio (BSR) values for efflux pump and beta-lactamase genes identified in Acinetobacter.

BSR values were visualized with the multi-experiment viewer . Accession details for each gene are shown in Table S3, with raw data shown in Table S5.