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The Role of CHI3L1 (Chitinase-3-Like-1) in the Pathogenesis of Infections in Burns in a Mouse Model.

Bohr S, Patel SJ, Vasko R, Shen K, Golberg A, Berthiaume F, Yarmush ML - PLoS ONE (2015)

Bottom Line: Increasing evidence supports the notion that inhibition of bacterial translocation into the wound site may be an effective alternative to prevent infection.In this context we investigated the role of the mammalian Chitinase-3-Like-1 (CHI3L1) non-enyzmatic protein predominately expressed on epithelial as well as innate immune cells as a potential bacterial-translocation-mediating factor.We show a strong trend that a modulation of chitinase expression is likely to be effective in reducing mortality rates in a mouse model of burn injury with superinfection with the opportunistic PA14 Pseudomonas strain, thus demonstrating possible clinical leverage.

View Article: PubMed Central - PubMed

Affiliation: Center for Engineering in Medicine, Shriners Hospitals for Children and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America; Department Plastic and Hand Surgery-Burn Center, UKA University Clinics RWTH, Aachen, Germany.

ABSTRACT
In severe burn injury the unique setting of a depleted, dysfunctional immune system along with a loss of barrier function commonly results in opportunistic infections that eventually proof fatal. Unfortunately, the dynamic sequence of bacterial contamination, colonization and eventually septic invasion with bacteria such as Pseudomonas species is still poorly understood although a limiting factor in clinical decision making. Increasing evidence supports the notion that inhibition of bacterial translocation into the wound site may be an effective alternative to prevent infection. In this context we investigated the role of the mammalian Chitinase-3-Like-1 (CHI3L1) non-enyzmatic protein predominately expressed on epithelial as well as innate immune cells as a potential bacterial-translocation-mediating factor. We show a strong trend that a modulation of chitinase expression is likely to be effective in reducing mortality rates in a mouse model of burn injury with superinfection with the opportunistic PA14 Pseudomonas strain, thus demonstrating possible clinical leverage.

No MeSH data available.


Related in: MedlinePlus

Chitin and chitosan modulate the expression of virulence factors in PA14 Pseudomonas strain.Several factors related to the pathogenicity of Pseudomonas species were evaluated following the addition of chitin (hmv poly-D-glucosamine) and chitosan (lmw poly-D-glucosamine) to lysogeny broth (LB). (A) Chitin-binding-protein Delta (CbpD) is strongly induced early on during the exponential growth phase (EGP) of PA14 strain. (B) Addition of both chitin and chitosan to LB further induces CbpD expression. (C) Various other factors of PA14 pathogenicity are also predominantly expressed during early EGP. (D) However, addition of chitin to LB only further induces ElastaseB but not other virulence factors (all: qPCR /ΔΔCt-method: n≥3; mean±SD; *P<0.05; normalized to a stationary bacterial growth phase control).
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pone.0140440.g005: Chitin and chitosan modulate the expression of virulence factors in PA14 Pseudomonas strain.Several factors related to the pathogenicity of Pseudomonas species were evaluated following the addition of chitin (hmv poly-D-glucosamine) and chitosan (lmw poly-D-glucosamine) to lysogeny broth (LB). (A) Chitin-binding-protein Delta (CbpD) is strongly induced early on during the exponential growth phase (EGP) of PA14 strain. (B) Addition of both chitin and chitosan to LB further induces CbpD expression. (C) Various other factors of PA14 pathogenicity are also predominantly expressed during early EGP. (D) However, addition of chitin to LB only further induces ElastaseB but not other virulence factors (all: qPCR /ΔΔCt-method: n≥3; mean±SD; *P<0.05; normalized to a stationary bacterial growth phase control).

Mentions: The induction of chitinases is related to an innate immune response which might favor infections with pathogens such as PS which can specifically interact with chitinase e.g. through the expression of chitin-binding proteins (CBPs). Mammalian CHI3L1 has been demonstrated as a possible ligand of CbpD along with chitin and chitin derivatives, thus implying a possible role in PA14 virulence. In this context we show that the addition of chitin and chitosan to LB bacterial growth media induces CbpD expression during an exponential growth phase (EGP) (Fig 5A). In addition we saw that low molecular chitosan induced CbpD more effectively than chitin (Fig 5B). During early EGP, PA14 also constitutively expresses various virulence factors related to a clinical relevant infection (Fig 5C). Here, we saw that elastaseB, but no other virulence factors, were specifically induced in PA14 by chitin supplemented growth media, consistent with an environmental ‘sensing-function’ of CbpD during PA14-related opportunistic infection [39] (Fig 5D). Thus, Pseudomonas is likely to specifically alter its transcriptional behavior in a wound environment or epithelial surface in the presence of possible ligands for CbpD such as chitinases, chitin or chitosan.


The Role of CHI3L1 (Chitinase-3-Like-1) in the Pathogenesis of Infections in Burns in a Mouse Model.

Bohr S, Patel SJ, Vasko R, Shen K, Golberg A, Berthiaume F, Yarmush ML - PLoS ONE (2015)

Chitin and chitosan modulate the expression of virulence factors in PA14 Pseudomonas strain.Several factors related to the pathogenicity of Pseudomonas species were evaluated following the addition of chitin (hmv poly-D-glucosamine) and chitosan (lmw poly-D-glucosamine) to lysogeny broth (LB). (A) Chitin-binding-protein Delta (CbpD) is strongly induced early on during the exponential growth phase (EGP) of PA14 strain. (B) Addition of both chitin and chitosan to LB further induces CbpD expression. (C) Various other factors of PA14 pathogenicity are also predominantly expressed during early EGP. (D) However, addition of chitin to LB only further induces ElastaseB but not other virulence factors (all: qPCR /ΔΔCt-method: n≥3; mean±SD; *P<0.05; normalized to a stationary bacterial growth phase control).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631332&req=5

pone.0140440.g005: Chitin and chitosan modulate the expression of virulence factors in PA14 Pseudomonas strain.Several factors related to the pathogenicity of Pseudomonas species were evaluated following the addition of chitin (hmv poly-D-glucosamine) and chitosan (lmw poly-D-glucosamine) to lysogeny broth (LB). (A) Chitin-binding-protein Delta (CbpD) is strongly induced early on during the exponential growth phase (EGP) of PA14 strain. (B) Addition of both chitin and chitosan to LB further induces CbpD expression. (C) Various other factors of PA14 pathogenicity are also predominantly expressed during early EGP. (D) However, addition of chitin to LB only further induces ElastaseB but not other virulence factors (all: qPCR /ΔΔCt-method: n≥3; mean±SD; *P<0.05; normalized to a stationary bacterial growth phase control).
Mentions: The induction of chitinases is related to an innate immune response which might favor infections with pathogens such as PS which can specifically interact with chitinase e.g. through the expression of chitin-binding proteins (CBPs). Mammalian CHI3L1 has been demonstrated as a possible ligand of CbpD along with chitin and chitin derivatives, thus implying a possible role in PA14 virulence. In this context we show that the addition of chitin and chitosan to LB bacterial growth media induces CbpD expression during an exponential growth phase (EGP) (Fig 5A). In addition we saw that low molecular chitosan induced CbpD more effectively than chitin (Fig 5B). During early EGP, PA14 also constitutively expresses various virulence factors related to a clinical relevant infection (Fig 5C). Here, we saw that elastaseB, but no other virulence factors, were specifically induced in PA14 by chitin supplemented growth media, consistent with an environmental ‘sensing-function’ of CbpD during PA14-related opportunistic infection [39] (Fig 5D). Thus, Pseudomonas is likely to specifically alter its transcriptional behavior in a wound environment or epithelial surface in the presence of possible ligands for CbpD such as chitinases, chitin or chitosan.

Bottom Line: Increasing evidence supports the notion that inhibition of bacterial translocation into the wound site may be an effective alternative to prevent infection.In this context we investigated the role of the mammalian Chitinase-3-Like-1 (CHI3L1) non-enyzmatic protein predominately expressed on epithelial as well as innate immune cells as a potential bacterial-translocation-mediating factor.We show a strong trend that a modulation of chitinase expression is likely to be effective in reducing mortality rates in a mouse model of burn injury with superinfection with the opportunistic PA14 Pseudomonas strain, thus demonstrating possible clinical leverage.

View Article: PubMed Central - PubMed

Affiliation: Center for Engineering in Medicine, Shriners Hospitals for Children and Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America; Department Plastic and Hand Surgery-Burn Center, UKA University Clinics RWTH, Aachen, Germany.

ABSTRACT
In severe burn injury the unique setting of a depleted, dysfunctional immune system along with a loss of barrier function commonly results in opportunistic infections that eventually proof fatal. Unfortunately, the dynamic sequence of bacterial contamination, colonization and eventually septic invasion with bacteria such as Pseudomonas species is still poorly understood although a limiting factor in clinical decision making. Increasing evidence supports the notion that inhibition of bacterial translocation into the wound site may be an effective alternative to prevent infection. In this context we investigated the role of the mammalian Chitinase-3-Like-1 (CHI3L1) non-enyzmatic protein predominately expressed on epithelial as well as innate immune cells as a potential bacterial-translocation-mediating factor. We show a strong trend that a modulation of chitinase expression is likely to be effective in reducing mortality rates in a mouse model of burn injury with superinfection with the opportunistic PA14 Pseudomonas strain, thus demonstrating possible clinical leverage.

No MeSH data available.


Related in: MedlinePlus