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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 positioning of genes encoding components of the Type VI secretion system. The complete genomes (horizontal black lines) have been shown to scale. The black arrows indicate the position of the cluster encoding the type VI secretion system; this cluster is not present in strain D1279779 with the grey arrow pointing to its predicted position. The rectangles indicate vgrG-like genes, their genomic position and the color show orthology (E-value <10-30). No significant similarity was seen between those represented in white. Rectangles without borders represent disrupted vgrG-like genes. The genomic position of genes encoding PAAR-repeat domain proteins has been indicated by the block-arrows. The color indicates to which class the encoded PAAR-repeat domain belongs; class 1 (red), class 2 (black) and class 5 (blue).
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Fig3: Genomic positioning of genes encoding components of the Type VI secretion system. The complete genomes (horizontal black lines) have been shown to scale. The black arrows indicate the position of the cluster encoding the type VI secretion system; this cluster is not present in strain D1279779 with the grey arrow pointing to its predicted position. The rectangles indicate vgrG-like genes, their genomic position and the color show orthology (E-value <10-30). No significant similarity was seen between those represented in white. Rectangles without borders represent disrupted vgrG-like genes. The genomic position of genes encoding PAAR-repeat domain proteins has been indicated by the block-arrows. The color indicates to which class the encoded PAAR-repeat domain belongs; class 1 (red), class 2 (black) and class 5 (blue).

Mentions: Three different types of putative effectors of the A. baumannii T6SSs have been identified; Hcp (hemolysis co-regulated protein), which is encoded by the highly conserved gene A1S_1296 (co-expressed with the other structural components of the T6SS), and a multitude of Valine-Glycine-Repeat protein G-like (VgrG-like) and Proline-Alanine-Alanine-Arginine (PAAR)-repeat domain proteins. Despite the high levels of homology observed between most T6SS clusters, the genes encoding the VgrG and PAAR-repeat domain proteins were found to be scattered throughout the genomes and only a few of these were found to be conserved between strains (Figure 3). The scattering of vgr-like genes is not unusual and has been documented in other bacteria such as Vibrio cholerae and E. coli where the vgr-like genes were initially thought to be accessory components of the recombination hot spot family [58, 59]. One of the genes annotated as a ‘Vgr-related’ protein encoded by A1S_3364 in strain ATCC 17978 was identified in all eight Acinetobacter strains, however, the C-terminal domain is highly variable. Furthermore, a major truncation of the gene encoding this VgrG protein appears to have occurred in strains ATCC 19606T and SDF, which likely renders it inactive. A number of vgrG genes were also identified in close proximity to the genomic position of the T6SS itself (Figure 3), which is not unusual and has been observed in numerous other bacteria [50]. However, the exact location of this gene, represented by A1S_1288 in strain ATCC 17978, differs and homologs can only be found in strains 6870155, AB0057, WM99c and ACICU. Overall, our comparative analyses indicated that at least 11 unique insertion events of vgrG have taken place in the eight A. baumannii strains included in this study (Figure 3). Most strains harbor three full-length vgrG genes, including D1279779, which does not possess the T6SS itself; ACICU possesses four.Figure 3


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

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

Genomic positioning of genes encoding components of the Type VI secretion system. The complete genomes (horizontal black lines) have been shown to scale. The black arrows indicate the position of the cluster encoding the type VI secretion system; this cluster is not present in strain D1279779 with the grey arrow pointing to its predicted position. The rectangles indicate vgrG-like genes, their genomic position and the color show orthology (E-value <10-30). No significant similarity was seen between those represented in white. Rectangles without borders represent disrupted vgrG-like genes. The genomic position of genes encoding PAAR-repeat domain proteins has been indicated by the block-arrows. The color indicates to which class the encoded PAAR-repeat domain belongs; class 1 (red), class 2 (black) and class 5 (blue).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Genomic positioning of genes encoding components of the Type VI secretion system. The complete genomes (horizontal black lines) have been shown to scale. The black arrows indicate the position of the cluster encoding the type VI secretion system; this cluster is not present in strain D1279779 with the grey arrow pointing to its predicted position. The rectangles indicate vgrG-like genes, their genomic position and the color show orthology (E-value <10-30). No significant similarity was seen between those represented in white. Rectangles without borders represent disrupted vgrG-like genes. The genomic position of genes encoding PAAR-repeat domain proteins has been indicated by the block-arrows. The color indicates to which class the encoded PAAR-repeat domain belongs; class 1 (red), class 2 (black) and class 5 (blue).
Mentions: Three different types of putative effectors of the A. baumannii T6SSs have been identified; Hcp (hemolysis co-regulated protein), which is encoded by the highly conserved gene A1S_1296 (co-expressed with the other structural components of the T6SS), and a multitude of Valine-Glycine-Repeat protein G-like (VgrG-like) and Proline-Alanine-Alanine-Arginine (PAAR)-repeat domain proteins. Despite the high levels of homology observed between most T6SS clusters, the genes encoding the VgrG and PAAR-repeat domain proteins were found to be scattered throughout the genomes and only a few of these were found to be conserved between strains (Figure 3). The scattering of vgr-like genes is not unusual and has been documented in other bacteria such as Vibrio cholerae and E. coli where the vgr-like genes were initially thought to be accessory components of the recombination hot spot family [58, 59]. One of the genes annotated as a ‘Vgr-related’ protein encoded by A1S_3364 in strain ATCC 17978 was identified in all eight Acinetobacter strains, however, the C-terminal domain is highly variable. Furthermore, a major truncation of the gene encoding this VgrG protein appears to have occurred in strains ATCC 19606T and SDF, which likely renders it inactive. A number of vgrG genes were also identified in close proximity to the genomic position of the T6SS itself (Figure 3), which is not unusual and has been observed in numerous other bacteria [50]. However, the exact location of this gene, represented by A1S_1288 in strain ATCC 17978, differs and homologs can only be found in strains 6870155, AB0057, WM99c and ACICU. Overall, our comparative analyses indicated that at least 11 unique insertion events of vgrG have taken place in the eight A. baumannii strains included in this study (Figure 3). Most strains harbor three full-length vgrG genes, including D1279779, which does not possess the T6SS itself; ACICU possesses four.Figure 3

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