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Autotransporters and Their Role in the Virulence of Burkholderia pseudomallei and Burkholderia mallei.

Lazar Adler NR, Stevens JM, Stevens MP, Galyov EE - Front Microbiol (2011)

Bottom Line: Autotransporters (ATs) comprise a large and diverse family of secreted and outer membrane proteins that includes virulence-associated invasins, adhesins, proteases, and actin-nucleating factors.Several predicted Burkholderia ATs are recognized by human humoral and cell-mediated immunity, indicating that they are expressed during infection and may be useful for diagnosis and vaccine-mediated protection.Further studies on the mode of secretion and functions of Burkholderia ATs will facilitate the rational design of control strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection, Immunity and Inflammation, University of Leicester Leicester, UK.

ABSTRACT
Burkholderia pseudomallei and Burkholderia mallei are closely related Gram-negative bacteria responsible for the infectious diseases melioidosis and glanders, respectively. Autotransporters (ATs) comprise a large and diverse family of secreted and outer membrane proteins that includes virulence-associated invasins, adhesins, proteases, and actin-nucleating factors. The B. pseudomallei K96243 genome contains 11 predicted ATs, eight of which share homologs in the B. mallei ATCC 23344 genome. This review distils key findings from in silico, in vitro, and in vivo studies on the ATs of B. pseudomallei and B. mallei. To date, the best characterized of the predicted ATs of B. pseudomallei and B. mallei is BimA, a predicted trimeric AT mediating actin-based motility which varies in sequence and mode of action between Burkholderia species. Of the remaining eight predicted B. pseudomallei trimeric autotransporters, five of which are also present in B. mallei, two (BoaA and BoaB), have been implicated in bacterial adhesion to epithelial cells. Several predicted Burkholderia ATs are recognized by human humoral and cell-mediated immunity, indicating that they are expressed during infection and may be useful for diagnosis and vaccine-mediated protection. Further studies on the mode of secretion and functions of Burkholderia ATs will facilitate the rational design of control strategies.

No MeSH data available.


Related in: MedlinePlus

Alignment and phylogenetic analysis of the β barrel domains of the putative B. pseudomallei and B. mallei TAAs: (A) the nine B. pseudomallei C-terminal 70–72 aa β barrel domains (B. mallei homologs 100% identical at this region) were aligned; identical residues are highlighted in red, those with high homology (at least 66%) in blue while those with highly conserved substitutions in green. The consensus sequence is listed below. (B) The phylogenetic analysis of these domains demonstrates two distinct clusters both of which derived from a common ancestor to the prototypical Yersinia YadA TAA.
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Figure 2: Alignment and phylogenetic analysis of the β barrel domains of the putative B. pseudomallei and B. mallei TAAs: (A) the nine B. pseudomallei C-terminal 70–72 aa β barrel domains (B. mallei homologs 100% identical at this region) were aligned; identical residues are highlighted in red, those with high homology (at least 66%) in blue while those with highly conserved substitutions in green. The consensus sequence is listed below. (B) The phylogenetic analysis of these domains demonstrates two distinct clusters both of which derived from a common ancestor to the prototypical Yersinia YadA TAA.

Mentions: Alignment of the C-terminal β barrel domain regions of the putative B. pseudomallei and B. mallei TAAs demonstrates considerable conservation indicative of amplification of these adhesins through gene duplication events (Figure 2A). This is potentially significant given the importance of C-terminal regions of TAAs in translocation and trimer stability, as evidenced by the ability of C-terminal domains of YadA family members from diverse bacteria to functionally replace the cognate domain in Yersinia (Ackermann et al., 2008). A phylogenetic tree of the β barrel domains is supportive of this idea as the TAAs form two clusters suggesting that these genes may have been amplified from two original ancestral genes (Figure 2B). Both clusters appear to be derived from a common ancestor to the prototypic Yersinia YadA TAA. Additionally, the two outliers in the alignment, BPSS0908/BMAA1324 and BPSS1434, display early separation in the phylogenetic tree. Interestingly, of the three unique B. pseudomallei TAAs, two (BPSS1434 and BPSS0088) are early branches in the phylogenetic tree suggesting that their absence from B. mallei is due to gene loss as later branching genes are present. Meanwhile BPSL1705, which is located within a genomic island (GI8), is very recently branched from BPSS0796/BMAA0649 and has been proposed to have originated as a duplication of BPSS0796/BMAA0649 (Tiyawisutsri et al., 2007). This duplication event may explain why BPSL1705 is the only AT not conserved across the four completed B. pseudomallei genomes. Furthermore, the β barrel domains of the B. pseudomallei and B. mallei TAA homologs show 100% identity although little similarity is seen between the passenger domains. However, the effector domains of TAAs are generally not conserved at a sequence level and the crystal structure analysis of a section of the passenger domain of BPSS1434 (re-annotated as BpaA, B. pseudomallei adhesion A) demonstrated quaternary structure similar to that of other TAAs (Edwards et al., 2010). This new annotation gives BPSS1434 the same name as the unrelated Type V two-partner secreted BpaA (Brown et al., 2004) for which no homolog exists in either B. pseudomallei K96243 or B. mallei ATCC 23344. The B. pseudomallei and B. mallei genomes contain homologs of BamA, BamB, and SurA which are proposed to assist in translocation of ATs across the OM (Ieva and Bernstein, 2009; Ruiz-Perez et al., 2009; Sauri et al., 2009; Lehr et al., 2010), and further studies are needed to evaluate the role of such factors in AT secretion and pathogenesis.


Autotransporters and Their Role in the Virulence of Burkholderia pseudomallei and Burkholderia mallei.

Lazar Adler NR, Stevens JM, Stevens MP, Galyov EE - Front Microbiol (2011)

Alignment and phylogenetic analysis of the β barrel domains of the putative B. pseudomallei and B. mallei TAAs: (A) the nine B. pseudomallei C-terminal 70–72 aa β barrel domains (B. mallei homologs 100% identical at this region) were aligned; identical residues are highlighted in red, those with high homology (at least 66%) in blue while those with highly conserved substitutions in green. The consensus sequence is listed below. (B) The phylogenetic analysis of these domains demonstrates two distinct clusters both of which derived from a common ancestor to the prototypical Yersinia YadA TAA.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3139927&req=5

Figure 2: Alignment and phylogenetic analysis of the β barrel domains of the putative B. pseudomallei and B. mallei TAAs: (A) the nine B. pseudomallei C-terminal 70–72 aa β barrel domains (B. mallei homologs 100% identical at this region) were aligned; identical residues are highlighted in red, those with high homology (at least 66%) in blue while those with highly conserved substitutions in green. The consensus sequence is listed below. (B) The phylogenetic analysis of these domains demonstrates two distinct clusters both of which derived from a common ancestor to the prototypical Yersinia YadA TAA.
Mentions: Alignment of the C-terminal β barrel domain regions of the putative B. pseudomallei and B. mallei TAAs demonstrates considerable conservation indicative of amplification of these adhesins through gene duplication events (Figure 2A). This is potentially significant given the importance of C-terminal regions of TAAs in translocation and trimer stability, as evidenced by the ability of C-terminal domains of YadA family members from diverse bacteria to functionally replace the cognate domain in Yersinia (Ackermann et al., 2008). A phylogenetic tree of the β barrel domains is supportive of this idea as the TAAs form two clusters suggesting that these genes may have been amplified from two original ancestral genes (Figure 2B). Both clusters appear to be derived from a common ancestor to the prototypic Yersinia YadA TAA. Additionally, the two outliers in the alignment, BPSS0908/BMAA1324 and BPSS1434, display early separation in the phylogenetic tree. Interestingly, of the three unique B. pseudomallei TAAs, two (BPSS1434 and BPSS0088) are early branches in the phylogenetic tree suggesting that their absence from B. mallei is due to gene loss as later branching genes are present. Meanwhile BPSL1705, which is located within a genomic island (GI8), is very recently branched from BPSS0796/BMAA0649 and has been proposed to have originated as a duplication of BPSS0796/BMAA0649 (Tiyawisutsri et al., 2007). This duplication event may explain why BPSL1705 is the only AT not conserved across the four completed B. pseudomallei genomes. Furthermore, the β barrel domains of the B. pseudomallei and B. mallei TAA homologs show 100% identity although little similarity is seen between the passenger domains. However, the effector domains of TAAs are generally not conserved at a sequence level and the crystal structure analysis of a section of the passenger domain of BPSS1434 (re-annotated as BpaA, B. pseudomallei adhesion A) demonstrated quaternary structure similar to that of other TAAs (Edwards et al., 2010). This new annotation gives BPSS1434 the same name as the unrelated Type V two-partner secreted BpaA (Brown et al., 2004) for which no homolog exists in either B. pseudomallei K96243 or B. mallei ATCC 23344. The B. pseudomallei and B. mallei genomes contain homologs of BamA, BamB, and SurA which are proposed to assist in translocation of ATs across the OM (Ieva and Bernstein, 2009; Ruiz-Perez et al., 2009; Sauri et al., 2009; Lehr et al., 2010), and further studies are needed to evaluate the role of such factors in AT secretion and pathogenesis.

Bottom Line: Autotransporters (ATs) comprise a large and diverse family of secreted and outer membrane proteins that includes virulence-associated invasins, adhesins, proteases, and actin-nucleating factors.Several predicted Burkholderia ATs are recognized by human humoral and cell-mediated immunity, indicating that they are expressed during infection and may be useful for diagnosis and vaccine-mediated protection.Further studies on the mode of secretion and functions of Burkholderia ATs will facilitate the rational design of control strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection, Immunity and Inflammation, University of Leicester Leicester, UK.

ABSTRACT
Burkholderia pseudomallei and Burkholderia mallei are closely related Gram-negative bacteria responsible for the infectious diseases melioidosis and glanders, respectively. Autotransporters (ATs) comprise a large and diverse family of secreted and outer membrane proteins that includes virulence-associated invasins, adhesins, proteases, and actin-nucleating factors. The B. pseudomallei K96243 genome contains 11 predicted ATs, eight of which share homologs in the B. mallei ATCC 23344 genome. This review distils key findings from in silico, in vitro, and in vivo studies on the ATs of B. pseudomallei and B. mallei. To date, the best characterized of the predicted ATs of B. pseudomallei and B. mallei is BimA, a predicted trimeric AT mediating actin-based motility which varies in sequence and mode of action between Burkholderia species. Of the remaining eight predicted B. pseudomallei trimeric autotransporters, five of which are also present in B. mallei, two (BoaA and BoaB), have been implicated in bacterial adhesion to epithelial cells. Several predicted Burkholderia ATs are recognized by human humoral and cell-mediated immunity, indicating that they are expressed during infection and may be useful for diagnosis and vaccine-mediated protection. Further studies on the mode of secretion and functions of Burkholderia ATs will facilitate the rational design of control strategies.

No MeSH data available.


Related in: MedlinePlus