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Borrelia burgdorferi HtrA may promote dissemination and irritation.

Gherardini FC - Mol. Microbiol. (2013)

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Zoonotic Pathogens, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, Hamilton, MT, 59840, USA; National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USA.

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Four recent publications in Molecular Microbiology have begun to address the importance of a putative protease, BB0104, in the physiology and pathogenesis of Borrelia burgdorferi... BB0104 is a member of a large family of serine proteases designated as the high-temperature requirement (HtrA) protease family (reviewed in ; )... By biochemically ‘sensing’ the integrity of membrane proteins, HtrA proteases provide a monitoring system that allows the cells to adapt readily to changing environmental conditions... As a result of these functions, HtrA proteases play a significant role in the overall physiology of the bacteria... Recently, it has been shown in different bacterial pathogens that HtrA can play a significant role in the pathology of infections... For example, in Bacillus anthracis, a htrA deletion mutant (ΔhtrA) is dramatically reduced in virulence in guinea pigs (6 orders of magnitude) compared with the wild-type and complemented mutant strains... Recent papers published in Molecular Microbiology present data that begin to shed light on the role of an HtrA homolgue, BB0104 (BbHtrA), in the physiology and pathogenesis of the Lyme disease agent, Borrelia burgdorferi... Chemokine and cytokine levels have been shown to be elevated in the epidermis of patients with erythema migrans, in the cerebrospinal fluid patients with neuroborreliosis and in the synovial fluid of patients with LA... These results thus suggest that BbHtrA, along with B.  burgdorferi lipoproteins, contribute to the pathology of neuroborreliosis and LA... The accumulating data published in Molecular Microbiology regarding BbHtrA demonstrate the importance of this protein in the physiology and pathogenesis of B.  burgdorferi ( Fig.  1)... Additionally, proteolytic activity of BbHtrA against aggrecan, a key structural proteoglycan present in connective tissue and joints, suggests a direct role in LA has been shown... More importantly, Russell et al. provide convincing data that HtrA is able to degrade fibronectin and various proteoglycans found in joints, epidermis and neurological tissues... Most significant, purified recombinant BbHtrA interacted with chondrocytes triggering the release of chemokines and pro-inflammatory cytokines... It seems very clear from these data that BbHtrA is critical in the physiology and pathogenesis of B.  burgdorferi.

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A model for the different activities linked to BbHtrA.
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fig01: A model for the different activities linked to BbHtrA.

Mentions: The accumulating data published in Molecular Microbiology regarding BbHtrA demonstrate the importance of this protein in the physiology and pathogenesis of B. burgdorferi ( Fig. 1). The protein is reported to be involved in the localization and processing of putative virulence factors, such as BB0323 and BmpD (Coleman et al., 2013; Kariu et al., 2013). Additionally, proteolytic activity of BbHtrA against aggrecan, a key structural proteoglycan present in connective tissue and joints, suggests a direct role in LA has been shown (Russell and Johnson, 2013). More importantly, Russell et al. provide convincing data that HtrA is able to degrade fibronectin and various proteoglycans found in joints, epidermis and neurological tissues. Most significant, purified recombinant BbHtrA interacted with chondrocytes triggering the release of chemokines and pro-inflammatory cytokines (Russell et al., 2013). These data indicate that HtrA is potentially important in cell physiology (motility, chemotaxis), protein processing (BB0323), bacterial dissemination (e.g. degradation of E-cadherin and aggrecan) and actively contributes to release of inflammatory cytokines (IL-6 and slCAM-1) and chemokines (e.g. CXCL1, CCL1, etc.) from cultured chondrocytes. It seems very clear from these data that BbHtrA is critical in the physiology and pathogenesis of B. burgdorferi.


Borrelia burgdorferi HtrA may promote dissemination and irritation.

Gherardini FC - Mol. Microbiol. (2013)

A model for the different activities linked to BbHtrA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260139&req=5

fig01: A model for the different activities linked to BbHtrA.
Mentions: The accumulating data published in Molecular Microbiology regarding BbHtrA demonstrate the importance of this protein in the physiology and pathogenesis of B. burgdorferi ( Fig. 1). The protein is reported to be involved in the localization and processing of putative virulence factors, such as BB0323 and BmpD (Coleman et al., 2013; Kariu et al., 2013). Additionally, proteolytic activity of BbHtrA against aggrecan, a key structural proteoglycan present in connective tissue and joints, suggests a direct role in LA has been shown (Russell and Johnson, 2013). More importantly, Russell et al. provide convincing data that HtrA is able to degrade fibronectin and various proteoglycans found in joints, epidermis and neurological tissues. Most significant, purified recombinant BbHtrA interacted with chondrocytes triggering the release of chemokines and pro-inflammatory cytokines (Russell et al., 2013). These data indicate that HtrA is potentially important in cell physiology (motility, chemotaxis), protein processing (BB0323), bacterial dissemination (e.g. degradation of E-cadherin and aggrecan) and actively contributes to release of inflammatory cytokines (IL-6 and slCAM-1) and chemokines (e.g. CXCL1, CCL1, etc.) from cultured chondrocytes. It seems very clear from these data that BbHtrA is critical in the physiology and pathogenesis of B. burgdorferi.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Zoonotic Pathogens, Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, Hamilton, MT, 59840, USA; National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USA.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Four recent publications in Molecular Microbiology have begun to address the importance of a putative protease, BB0104, in the physiology and pathogenesis of Borrelia burgdorferi... BB0104 is a member of a large family of serine proteases designated as the high-temperature requirement (HtrA) protease family (reviewed in ; )... By biochemically ‘sensing’ the integrity of membrane proteins, HtrA proteases provide a monitoring system that allows the cells to adapt readily to changing environmental conditions... As a result of these functions, HtrA proteases play a significant role in the overall physiology of the bacteria... Recently, it has been shown in different bacterial pathogens that HtrA can play a significant role in the pathology of infections... For example, in Bacillus anthracis, a htrA deletion mutant (ΔhtrA) is dramatically reduced in virulence in guinea pigs (6 orders of magnitude) compared with the wild-type and complemented mutant strains... Recent papers published in Molecular Microbiology present data that begin to shed light on the role of an HtrA homolgue, BB0104 (BbHtrA), in the physiology and pathogenesis of the Lyme disease agent, Borrelia burgdorferi... Chemokine and cytokine levels have been shown to be elevated in the epidermis of patients with erythema migrans, in the cerebrospinal fluid patients with neuroborreliosis and in the synovial fluid of patients with LA... These results thus suggest that BbHtrA, along with B.  burgdorferi lipoproteins, contribute to the pathology of neuroborreliosis and LA... The accumulating data published in Molecular Microbiology regarding BbHtrA demonstrate the importance of this protein in the physiology and pathogenesis of B.  burgdorferi ( Fig.  1)... Additionally, proteolytic activity of BbHtrA against aggrecan, a key structural proteoglycan present in connective tissue and joints, suggests a direct role in LA has been shown... More importantly, Russell et al. provide convincing data that HtrA is able to degrade fibronectin and various proteoglycans found in joints, epidermis and neurological tissues... Most significant, purified recombinant BbHtrA interacted with chondrocytes triggering the release of chemokines and pro-inflammatory cytokines... It seems very clear from these data that BbHtrA is critical in the physiology and pathogenesis of B.  burgdorferi.

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