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Comparative analysis of surface-exposed virulence factors of Acinetobacter baumannii.

Eijkelkamp BA, Stroeher UH, Hassan KA, Paulsen IT, Brown MH - BMC Genomics (2014)

Bottom Line: Acinetobacter baumannii is a significant hospital pathogen, particularly due to the dissemination of highly multidrug resistant isolates.This appears to have facilitated the expansion of its repertoire of virulence traits, as in general, the nosocomial strains in this study possess more virulence genes compared to the community-acquired isolate.Overall, these analyses increase our understanding of A. baumannii pathogenicity and will assist in future studies determining the significance of virulence factors within clonal lineages and/or across the species.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, Flinders University, Adelaide, Australia. melissa.brown@flinders.edu.au.

ABSTRACT

Background: Acinetobacter baumannii is a significant hospital pathogen, particularly due to the dissemination of highly multidrug resistant isolates. Genome data have revealed that A. baumannii is highly genetically diverse, which correlates with major variations seen at the phenotypic level. Thus far, comparative genomic studies have been aimed at identifying resistance determinants in A. baumannii. In this study, we extend and expand on these analyses to gain greater insight into the virulence factors across eight A. baumannii strains which are clonally, temporally and geographically distinct, and includes an isolate considered non-pathogenic and a community-acquired A. baumannii.

Results: We have identified a large number of genes in the A. baumannii genomes that are known to play a role in virulence in other pathogens, such as the recently studied proline-alanine-alanine-arginine (PAAR)-repeat domains of the type VI secretion systems. Not surprising, many virulence candidates appear to be part of the A. baumannii core genome of virulent isolates but were often found to be insertionally disrupted in the avirulent A. baumannii strain SDF. Our study also reveals that many known or putative virulence determinants are restricted to specific clonal lineages, which suggests that these virulence determinants may be crucial for the success of these widespread common clones. It has previously been suggested that the high level of intrinsic and adaptive resistance has enabled the widespread presence of A. baumannii in the hospital environment. This appears to have facilitated the expansion of its repertoire of virulence traits, as in general, the nosocomial strains in this study possess more virulence genes compared to the community-acquired isolate.

Conclusions: Major genetic variation in known or putative virulence factors was seen across the eight strains included in this study, suggesting that virulence mechanisms are complex and multifaceted in A. baumannii. Overall, these analyses increase our understanding of A. baumannii pathogenicity and will assist in future studies determining the significance of virulence factors within clonal lineages and/or across the species.

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Genomic diversity amongAcinetobacterstrains. (A) Partial Venn diagram. Each A. baumannii strain is depicted by an oval colored according to IC designation. Numbers presented in overlapping regions of the ovals show the number of genes shared by that group of strains. For example, the core genome size shown in the center, where all ovals overlap, is 1560 ORFs. Numbers in the non-overlapping regions show the number of genes unique to that strain. (B) Phylogenetic tree based on a concatenated alignment of the core housekeeping genes cpn60, fusA, gltA, pyrG, recA, rplB and rpoB in the strains under investigation. A. baylyi ADP1 (GenBank; CR543861) was used as an outgroup and the dotted line used in the ADP1 branch indicates a branch length greater than that shown. Numbers to the right of the tree show the size of the total number of conserved ORFs (the core genome) in the set of strains indicated.
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Fig1: Genomic diversity amongAcinetobacterstrains. (A) Partial Venn diagram. Each A. baumannii strain is depicted by an oval colored according to IC designation. Numbers presented in overlapping regions of the ovals show the number of genes shared by that group of strains. For example, the core genome size shown in the center, where all ovals overlap, is 1560 ORFs. Numbers in the non-overlapping regions show the number of genes unique to that strain. (B) Phylogenetic tree based on a concatenated alignment of the core housekeeping genes cpn60, fusA, gltA, pyrG, recA, rplB and rpoB in the strains under investigation. A. baylyi ADP1 (GenBank; CR543861) was used as an outgroup and the dotted line used in the ADP1 branch indicates a branch length greater than that shown. Numbers to the right of the tree show the size of the total number of conserved ORFs (the core genome) in the set of strains indicated.

Mentions: A genome-wide analysis of the shared gene content was performed which showed that 1560 genes were shared between all eight strains, which can be considered the “core genome”. However, strain SDF has undergone major genomic rearrangements and the remaining seven strains have an additional 503 shared genes, hence, 2063 genes were shared between the virulent strains included in this study. In respect to divergence from the core genome (1560 genes), strain ATCC 17978 was found to possess the highest number of unique genes (n = 819) followed by the SDF isolate (n = 606) (Figure 1A). The direct genome comparison revealed that clonality, examined as described previously [33], correlated with their total shared gene content; isolates within clonal groups showed the highest percentage of shared genes as compared to strains from different clonal groups (Figure 1B; Additional file 1). Strain SDF shared the lowest number of genes with other isolates. However, since SDF has a small genome that has undergone considerable genome reduction (only ~3050 open reading frames) it still shared an average of approximately 71% of its coding content with the other isolates used in this analysis. Strain ATCC 17978 also showed comparatively low numbers of shared genes, potentially resulting from its temporal and/or geographic separation from the other strains. The highest proportion of shared genes was 92% between the two IC I isolates AB0057 and 6870155. Overall, these diverse strains exemplify an excellent representation of A. baumannii isolates for tracking the spread of virulence determinants, by including clonal strains commonly isolated worldwide (the IC strains), a community-acquired strain and strains that are geographically and temporally distant. The avirulent isolate SDF was predominantly included for comparative purposes.Figure 1


Comparative analysis of surface-exposed virulence factors of Acinetobacter baumannii.

Eijkelkamp BA, Stroeher UH, Hassan KA, Paulsen IT, Brown MH - BMC Genomics (2014)

Genomic diversity amongAcinetobacterstrains. (A) Partial Venn diagram. Each A. baumannii strain is depicted by an oval colored according to IC designation. Numbers presented in overlapping regions of the ovals show the number of genes shared by that group of strains. For example, the core genome size shown in the center, where all ovals overlap, is 1560 ORFs. Numbers in the non-overlapping regions show the number of genes unique to that strain. (B) Phylogenetic tree based on a concatenated alignment of the core housekeeping genes cpn60, fusA, gltA, pyrG, recA, rplB and rpoB in the strains under investigation. A. baylyi ADP1 (GenBank; CR543861) was used as an outgroup and the dotted line used in the ADP1 branch indicates a branch length greater than that shown. Numbers to the right of the tree show the size of the total number of conserved ORFs (the core genome) in the set of strains indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4256060&req=5

Fig1: Genomic diversity amongAcinetobacterstrains. (A) Partial Venn diagram. Each A. baumannii strain is depicted by an oval colored according to IC designation. Numbers presented in overlapping regions of the ovals show the number of genes shared by that group of strains. For example, the core genome size shown in the center, where all ovals overlap, is 1560 ORFs. Numbers in the non-overlapping regions show the number of genes unique to that strain. (B) Phylogenetic tree based on a concatenated alignment of the core housekeeping genes cpn60, fusA, gltA, pyrG, recA, rplB and rpoB in the strains under investigation. A. baylyi ADP1 (GenBank; CR543861) was used as an outgroup and the dotted line used in the ADP1 branch indicates a branch length greater than that shown. Numbers to the right of the tree show the size of the total number of conserved ORFs (the core genome) in the set of strains indicated.
Mentions: A genome-wide analysis of the shared gene content was performed which showed that 1560 genes were shared between all eight strains, which can be considered the “core genome”. However, strain SDF has undergone major genomic rearrangements and the remaining seven strains have an additional 503 shared genes, hence, 2063 genes were shared between the virulent strains included in this study. In respect to divergence from the core genome (1560 genes), strain ATCC 17978 was found to possess the highest number of unique genes (n = 819) followed by the SDF isolate (n = 606) (Figure 1A). The direct genome comparison revealed that clonality, examined as described previously [33], correlated with their total shared gene content; isolates within clonal groups showed the highest percentage of shared genes as compared to strains from different clonal groups (Figure 1B; Additional file 1). Strain SDF shared the lowest number of genes with other isolates. However, since SDF has a small genome that has undergone considerable genome reduction (only ~3050 open reading frames) it still shared an average of approximately 71% of its coding content with the other isolates used in this analysis. Strain ATCC 17978 also showed comparatively low numbers of shared genes, potentially resulting from its temporal and/or geographic separation from the other strains. The highest proportion of shared genes was 92% between the two IC I isolates AB0057 and 6870155. Overall, these diverse strains exemplify an excellent representation of A. baumannii isolates for tracking the spread of virulence determinants, by including clonal strains commonly isolated worldwide (the IC strains), a community-acquired strain and strains that are geographically and temporally distant. The avirulent isolate SDF was predominantly included for comparative purposes.Figure 1

Bottom Line: Acinetobacter baumannii is a significant hospital pathogen, particularly due to the dissemination of highly multidrug resistant isolates.This appears to have facilitated the expansion of its repertoire of virulence traits, as in general, the nosocomial strains in this study possess more virulence genes compared to the community-acquired isolate.Overall, these analyses increase our understanding of A. baumannii pathogenicity and will assist in future studies determining the significance of virulence factors within clonal lineages and/or across the species.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, Flinders University, Adelaide, Australia. melissa.brown@flinders.edu.au.

ABSTRACT

Background: Acinetobacter baumannii is a significant hospital pathogen, particularly due to the dissemination of highly multidrug resistant isolates. Genome data have revealed that A. baumannii is highly genetically diverse, which correlates with major variations seen at the phenotypic level. Thus far, comparative genomic studies have been aimed at identifying resistance determinants in A. baumannii. In this study, we extend and expand on these analyses to gain greater insight into the virulence factors across eight A. baumannii strains which are clonally, temporally and geographically distinct, and includes an isolate considered non-pathogenic and a community-acquired A. baumannii.

Results: We have identified a large number of genes in the A. baumannii genomes that are known to play a role in virulence in other pathogens, such as the recently studied proline-alanine-alanine-arginine (PAAR)-repeat domains of the type VI secretion systems. Not surprising, many virulence candidates appear to be part of the A. baumannii core genome of virulent isolates but were often found to be insertionally disrupted in the avirulent A. baumannii strain SDF. Our study also reveals that many known or putative virulence determinants are restricted to specific clonal lineages, which suggests that these virulence determinants may be crucial for the success of these widespread common clones. It has previously been suggested that the high level of intrinsic and adaptive resistance has enabled the widespread presence of A. baumannii in the hospital environment. This appears to have facilitated the expansion of its repertoire of virulence traits, as in general, the nosocomial strains in this study possess more virulence genes compared to the community-acquired isolate.

Conclusions: Major genetic variation in known or putative virulence factors was seen across the eight strains included in this study, suggesting that virulence mechanisms are complex and multifaceted in A. baumannii. Overall, these analyses increase our understanding of A. baumannii pathogenicity and will assist in future studies determining the significance of virulence factors within clonal lineages and/or across the species.

Show MeSH
Related in: MedlinePlus