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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 region involved in production and secretion of capsule. Genomic organization of the region involved in capsule biosynthesis. Genes have been drawn to scale. The arrows represent ORFs and depict the direction of transcription; capsule biosynthesis genes (black), adjacent homologous genes (grey) and transposases (red). The blue shading indicates a high level of homology between genes from different strains (E-value <10-30).
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Fig4: Genomic region involved in production and secretion of capsule. Genomic organization of the region involved in capsule biosynthesis. Genes have been drawn to scale. The arrows represent ORFs and depict the direction of transcription; capsule biosynthesis genes (black), adjacent homologous genes (grey) and transposases (red). The blue shading indicates a high level of homology between genes from different strains (E-value <10-30).

Mentions: The O antigen and/or the capsule have long been recognized as essential virulence factors in numerous bacterial species as mutants that are either rough (contain no O antigen) or acapsular are generally avirulent [75]. By definition, O antigen is linked to the outer core of the lipopolysaccharide (LPS), which constitutes the outer leaflet of the outer membrane in Gram-negative organisms, whereas a capsule is generally considered to be unlinked or linked to the cell wall. There is mounting evidence that A. baumannii produces capsule [76–79], because the waaL gene is lacking within the surface polysaccharide operon. WaaL is required for linking O antigen to the outer core, thus these strains are likely to produce capsule and not O antigen. A waaL-like gene present elsewhere in A. baumannii genomes was thought to be involved in protein glycosylation and not O-antigen linkage [80]. However, Wright et al.[81], has suggested that a second waaL gene present in some strains of A. baumannii may actually be involved in O-antigen linkage as this second gene does not have the domain thought to be required for protein glycosylation [81]. Examination of the strains in our study showed that only the EC II clone strains (ACICU and WM99c) and ATCC 19606T and 6870155 possessed homologs of this second waaL-like gene (Table 3). Comparison of the genome organization of ATCC 17978 encompassing ORFs A1S_0049 to A1S_0066 (Figure 4; Table 3) with the other seven strains used in this study indicates at least six different genetic arrangements of this region, which would imply six different capsule types. This supports the notion that many distinct cluster types may be present across the species [76, 77, 79]. At the start of this region there are four conserved ORFs (A1S_0049-0052). Adjacent to these highly conserved genes is a genetic region of higher variability, encoding proteins involved in the biosynthesis of specific activated sugar precursors and transferases for each of the capsule types. The last section of this locus contains a second conserved region of five ORFs (A1S_0062 to A1S_0066).Table 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 region involved in production and secretion of capsule. Genomic organization of the region involved in capsule biosynthesis. Genes have been drawn to scale. The arrows represent ORFs and depict the direction of transcription; capsule biosynthesis genes (black), adjacent homologous genes (grey) and transposases (red). The blue shading indicates a high level of homology between genes from different strains (E-value <10-30).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Genomic region involved in production and secretion of capsule. Genomic organization of the region involved in capsule biosynthesis. Genes have been drawn to scale. The arrows represent ORFs and depict the direction of transcription; capsule biosynthesis genes (black), adjacent homologous genes (grey) and transposases (red). The blue shading indicates a high level of homology between genes from different strains (E-value <10-30).
Mentions: The O antigen and/or the capsule have long been recognized as essential virulence factors in numerous bacterial species as mutants that are either rough (contain no O antigen) or acapsular are generally avirulent [75]. By definition, O antigen is linked to the outer core of the lipopolysaccharide (LPS), which constitutes the outer leaflet of the outer membrane in Gram-negative organisms, whereas a capsule is generally considered to be unlinked or linked to the cell wall. There is mounting evidence that A. baumannii produces capsule [76–79], because the waaL gene is lacking within the surface polysaccharide operon. WaaL is required for linking O antigen to the outer core, thus these strains are likely to produce capsule and not O antigen. A waaL-like gene present elsewhere in A. baumannii genomes was thought to be involved in protein glycosylation and not O-antigen linkage [80]. However, Wright et al.[81], has suggested that a second waaL gene present in some strains of A. baumannii may actually be involved in O-antigen linkage as this second gene does not have the domain thought to be required for protein glycosylation [81]. Examination of the strains in our study showed that only the EC II clone strains (ACICU and WM99c) and ATCC 19606T and 6870155 possessed homologs of this second waaL-like gene (Table 3). Comparison of the genome organization of ATCC 17978 encompassing ORFs A1S_0049 to A1S_0066 (Figure 4; Table 3) with the other seven strains used in this study indicates at least six different genetic arrangements of this region, which would imply six different capsule types. This supports the notion that many distinct cluster types may be present across the species [76, 77, 79]. At the start of this region there are four conserved ORFs (A1S_0049-0052). Adjacent to these highly conserved genes is a genetic region of higher variability, encoding proteins involved in the biosynthesis of specific activated sugar precursors and transferases for each of the capsule types. The last section of this locus contains a second conserved region of five ORFs (A1S_0062 to A1S_0066).Table 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