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Protection against Mycobacterium ulcerans lesion development by exposure to aquatic insect saliva.

Marsollier L, Deniaux E, Brodin P, Marot A, Wondje CM, Saint-André JP, Chauty A, Johnson C, Tekaia F, Yeramian E, Legras P, Carbonnelle B, Reysset G, Eyangoh S, Milon G, Cole ST, Aubry J - PLoS Med. (2007)

Bottom Line: Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment.Then using human serum samples collected in a Buruli ulcer-endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies.IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France. laurentmarsollier@hotmail.com

ABSTRACT

Background: Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment. The mode of transmission of this Mycobacterium species remains a matter of debate, and relevant interventions to prevent this disease lack (i) the proper understanding of the M. ulcerans life history traits in its natural aquatic ecosystem and (ii) immune signatures that could be correlates of protection. We previously set up a laboratory ecosystem with predatory aquatic insects of the family Naucoridae and laboratory mice and showed that (i) M. ulcerans-carrying aquatic insects can transmit the mycobacterium through bites and (ii) that their salivary glands are the only tissues hosting replicative M. ulcerans. Further investigation in natural settings revealed that 5%-10% of these aquatic insects captured in endemic areas have M. ulcerans-loaded salivary glands. In search of novel epidemiological features we noticed that individuals working close to aquatic environments inhabited by insect predators were less prone to developing Buruli ulcers than their relatives. Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection.

Methods and findings: We took a two-pronged approach in this study, first investigating whether the insect bites are protective in a mouse model, and subsequently looking for possibly protective immune signatures in humans. We found that, in contrast to control BALB/c mice, BALB/c mice exposed to Naucoris aquatic insect bites or sensitized to Naucoris salivary gland homogenates (SGHs) displayed no lesion at the site of inoculation of M. ulcerans coated with Naucoris SGH components. Then using human serum samples collected in a Buruli ulcer-endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies. IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.

Conclusions: These data will help structure future investigations in Buruli ulcer-endemic areas, providing a rationale for research into human immune signatures of exposure to predatory aquatic insects, with special attention to those insect saliva molecules that bind to M. ulcerans.

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Related in: MedlinePlus

Western Blotting to Detect the Presence in Mouse Sera of IgGs Binding to N. cimicoides SGH(A) Lane 1: Coomassie staining of N. cimicoides SGH. Lane 2: Blotting of SGH with serum from mice bitten by N. cimicoides. Lane 3: Blotting of SGH with serum from mice immunized with SGH. Lane 4: Blotting of SGH with preimmune mouse serum.(B) Lane 1: Coomassie staining of N. cimicoides SGH. Lane 2: Coomassie staining of SGH-derived molecules bound to M. ulcerans cluster: arrows 1 to 3 correspond to 72, 48, and 22 kDa molecules, respectively. Lane 3: Coomassie staining of whole M. ulcerans bacteria never exposed to SGH. Lane 4: Blotting of SGH-derived molecules bound to M. ulcerans with serum of mice bitten by M. ulcerans-free N. cimicoides.MW, molecular weight.
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pmed-0040064-g002: Western Blotting to Detect the Presence in Mouse Sera of IgGs Binding to N. cimicoides SGH(A) Lane 1: Coomassie staining of N. cimicoides SGH. Lane 2: Blotting of SGH with serum from mice bitten by N. cimicoides. Lane 3: Blotting of SGH with serum from mice immunized with SGH. Lane 4: Blotting of SGH with preimmune mouse serum.(B) Lane 1: Coomassie staining of N. cimicoides SGH. Lane 2: Coomassie staining of SGH-derived molecules bound to M. ulcerans cluster: arrows 1 to 3 correspond to 72, 48, and 22 kDa molecules, respectively. Lane 3: Coomassie staining of whole M. ulcerans bacteria never exposed to SGH. Lane 4: Blotting of SGH-derived molecules bound to M. ulcerans with serum of mice bitten by M. ulcerans-free N. cimicoides.MW, molecular weight.

Mentions: The sera of mice exposed or not to M. ulcerans-free insect bites were screened for the presence of IgGs that bind proteins present in the aquatic insect SGH. Many proteins from the SGH bound IgGs present in the sera of mice exposed to insect bites, whereas no binding was observed with sera from mice not exposed to insect bites (Figure 2A, lane 2 versus lane 4). Three SGH proteins (22, 48, and 72 kDa) were reproducibly recovered from M. ulcerans once the latter were coincubated with SGH (Figure 2B, lane 2). Among these, two proteins (22 and 48 kDa) did bind IgGs present in the serum of mice exposed to insect bites, indicating that these insect molecules were delivered to mice during the usual biting process (Figure 2B, lane 4). Altogether, these results show that the sera of mice bitten by N. cimicoides contain IgGs that bind SGH-derived molecules, two of which are retained by M. ulcerans clusters.


Protection against Mycobacterium ulcerans lesion development by exposure to aquatic insect saliva.

Marsollier L, Deniaux E, Brodin P, Marot A, Wondje CM, Saint-André JP, Chauty A, Johnson C, Tekaia F, Yeramian E, Legras P, Carbonnelle B, Reysset G, Eyangoh S, Milon G, Cole ST, Aubry J - PLoS Med. (2007)

Western Blotting to Detect the Presence in Mouse Sera of IgGs Binding to N. cimicoides SGH(A) Lane 1: Coomassie staining of N. cimicoides SGH. Lane 2: Blotting of SGH with serum from mice bitten by N. cimicoides. Lane 3: Blotting of SGH with serum from mice immunized with SGH. Lane 4: Blotting of SGH with preimmune mouse serum.(B) Lane 1: Coomassie staining of N. cimicoides SGH. Lane 2: Coomassie staining of SGH-derived molecules bound to M. ulcerans cluster: arrows 1 to 3 correspond to 72, 48, and 22 kDa molecules, respectively. Lane 3: Coomassie staining of whole M. ulcerans bacteria never exposed to SGH. Lane 4: Blotting of SGH-derived molecules bound to M. ulcerans with serum of mice bitten by M. ulcerans-free N. cimicoides.MW, molecular weight.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1808094&req=5

pmed-0040064-g002: Western Blotting to Detect the Presence in Mouse Sera of IgGs Binding to N. cimicoides SGH(A) Lane 1: Coomassie staining of N. cimicoides SGH. Lane 2: Blotting of SGH with serum from mice bitten by N. cimicoides. Lane 3: Blotting of SGH with serum from mice immunized with SGH. Lane 4: Blotting of SGH with preimmune mouse serum.(B) Lane 1: Coomassie staining of N. cimicoides SGH. Lane 2: Coomassie staining of SGH-derived molecules bound to M. ulcerans cluster: arrows 1 to 3 correspond to 72, 48, and 22 kDa molecules, respectively. Lane 3: Coomassie staining of whole M. ulcerans bacteria never exposed to SGH. Lane 4: Blotting of SGH-derived molecules bound to M. ulcerans with serum of mice bitten by M. ulcerans-free N. cimicoides.MW, molecular weight.
Mentions: The sera of mice exposed or not to M. ulcerans-free insect bites were screened for the presence of IgGs that bind proteins present in the aquatic insect SGH. Many proteins from the SGH bound IgGs present in the sera of mice exposed to insect bites, whereas no binding was observed with sera from mice not exposed to insect bites (Figure 2A, lane 2 versus lane 4). Three SGH proteins (22, 48, and 72 kDa) were reproducibly recovered from M. ulcerans once the latter were coincubated with SGH (Figure 2B, lane 2). Among these, two proteins (22 and 48 kDa) did bind IgGs present in the serum of mice exposed to insect bites, indicating that these insect molecules were delivered to mice during the usual biting process (Figure 2B, lane 4). Altogether, these results show that the sera of mice bitten by N. cimicoides contain IgGs that bind SGH-derived molecules, two of which are retained by M. ulcerans clusters.

Bottom Line: Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment.Then using human serum samples collected in a Buruli ulcer-endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies.IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France. laurentmarsollier@hotmail.com

ABSTRACT

Background: Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment. The mode of transmission of this Mycobacterium species remains a matter of debate, and relevant interventions to prevent this disease lack (i) the proper understanding of the M. ulcerans life history traits in its natural aquatic ecosystem and (ii) immune signatures that could be correlates of protection. We previously set up a laboratory ecosystem with predatory aquatic insects of the family Naucoridae and laboratory mice and showed that (i) M. ulcerans-carrying aquatic insects can transmit the mycobacterium through bites and (ii) that their salivary glands are the only tissues hosting replicative M. ulcerans. Further investigation in natural settings revealed that 5%-10% of these aquatic insects captured in endemic areas have M. ulcerans-loaded salivary glands. In search of novel epidemiological features we noticed that individuals working close to aquatic environments inhabited by insect predators were less prone to developing Buruli ulcers than their relatives. Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection.

Methods and findings: We took a two-pronged approach in this study, first investigating whether the insect bites are protective in a mouse model, and subsequently looking for possibly protective immune signatures in humans. We found that, in contrast to control BALB/c mice, BALB/c mice exposed to Naucoris aquatic insect bites or sensitized to Naucoris salivary gland homogenates (SGHs) displayed no lesion at the site of inoculation of M. ulcerans coated with Naucoris SGH components. Then using human serum samples collected in a Buruli ulcer-endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies. IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.

Conclusions: These data will help structure future investigations in Buruli ulcer-endemic areas, providing a rationale for research into human immune signatures of exposure to predatory aquatic insects, with special attention to those insect saliva molecules that bind to M. ulcerans.

Show MeSH
Related in: MedlinePlus