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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 with Human Serum Samples as Probes for SGH Molecules that Bound to M. ulceransN. flavicollis SGH molecules bound to M. ulcerans were size-fractionated and probed with human serum samples. Lane 1: M. ulcerans not preincubated with N. flavicollis SGH probed with serum from the patient group. Lane 2: M. ulcerans not preincubated with N. flavicollis SGH probed with serum from the exposed group. Lane 3: N. flavicollis SGH molecules that bind to M. ulcerans probed with serum from the patient group. Lane 4: N. flavicollis SGH molecules that bind to M. ulcerans probed with serum from the exposed group. Arrows indicate four M. ulcerans antigens. Arrow heads indicate five M. ulcerans-binding insect protein bands at 22, 35, 40, 48, and 66 kDa.MW, molecular weight.
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pmed-0040064-g004: Western Blotting with Human Serum Samples as Probes for SGH Molecules that Bound to M. ulceransN. flavicollis SGH molecules bound to M. ulcerans were size-fractionated and probed with human serum samples. Lane 1: M. ulcerans not preincubated with N. flavicollis SGH probed with serum from the patient group. Lane 2: M. ulcerans not preincubated with N. flavicollis SGH probed with serum from the exposed group. Lane 3: N. flavicollis SGH molecules that bind to M. ulcerans probed with serum from the patient group. Lane 4: N. flavicollis SGH molecules that bind to M. ulcerans probed with serum from the exposed group. Arrows indicate four M. ulcerans antigens. Arrow heads indicate five M. ulcerans-binding insect protein bands at 22, 35, 40, 48, and 66 kDa.MW, molecular weight.

Mentions: All sera from individuals living in areas of Benin endemic for Buruli ulcers were first screened by Western blotting for reactive antibodies against SGH prepared from the aquatic insects present in the endemic areas, namely N. flavicollis (Figure 3). Many of the SGH constituents, such as 22, 40, 48, and 54 kDa proteins, bound IgGs present in the sera of exposed group members. Surprisingly, none of the SGH proteins bound IgGs present in 27 of the 30 sera collected from the patient group. The IgGs in the sera from the exposed group bound five of the SGH-derived molecular species (22, 35, 40, 48, and 66 kDa) shown to coat M. ulcerans (Figure 4). IgGs from the sera of participants from both groups recognised four bands (32, 56, 85, and 172 kDa) from heat-killed M. ulcerans bacteria, which are likely due to common epitopes shared with other environmental mycobacteria (Figure 4). Altogether, this qualitative analysis showed the presence of SGH-binding IgGs primarily in the sera of exposed group members.


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 with Human Serum Samples as Probes for SGH Molecules that Bound to M. ulceransN. flavicollis SGH molecules bound to M. ulcerans were size-fractionated and probed with human serum samples. Lane 1: M. ulcerans not preincubated with N. flavicollis SGH probed with serum from the patient group. Lane 2: M. ulcerans not preincubated with N. flavicollis SGH probed with serum from the exposed group. Lane 3: N. flavicollis SGH molecules that bind to M. ulcerans probed with serum from the patient group. Lane 4: N. flavicollis SGH molecules that bind to M. ulcerans probed with serum from the exposed group. Arrows indicate four M. ulcerans antigens. Arrow heads indicate five M. ulcerans-binding insect protein bands at 22, 35, 40, 48, and 66 kDa.MW, molecular weight.
© Copyright Policy
Related In: Results  -  Collection

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

pmed-0040064-g004: Western Blotting with Human Serum Samples as Probes for SGH Molecules that Bound to M. ulceransN. flavicollis SGH molecules bound to M. ulcerans were size-fractionated and probed with human serum samples. Lane 1: M. ulcerans not preincubated with N. flavicollis SGH probed with serum from the patient group. Lane 2: M. ulcerans not preincubated with N. flavicollis SGH probed with serum from the exposed group. Lane 3: N. flavicollis SGH molecules that bind to M. ulcerans probed with serum from the patient group. Lane 4: N. flavicollis SGH molecules that bind to M. ulcerans probed with serum from the exposed group. Arrows indicate four M. ulcerans antigens. Arrow heads indicate five M. ulcerans-binding insect protein bands at 22, 35, 40, 48, and 66 kDa.MW, molecular weight.
Mentions: All sera from individuals living in areas of Benin endemic for Buruli ulcers were first screened by Western blotting for reactive antibodies against SGH prepared from the aquatic insects present in the endemic areas, namely N. flavicollis (Figure 3). Many of the SGH constituents, such as 22, 40, 48, and 54 kDa proteins, bound IgGs present in the sera of exposed group members. Surprisingly, none of the SGH proteins bound IgGs present in 27 of the 30 sera collected from the patient group. The IgGs in the sera from the exposed group bound five of the SGH-derived molecular species (22, 35, 40, 48, and 66 kDa) shown to coat M. ulcerans (Figure 4). IgGs from the sera of participants from both groups recognised four bands (32, 56, 85, and 172 kDa) from heat-killed M. ulcerans bacteria, which are likely due to common epitopes shared with other environmental mycobacteria (Figure 4). Altogether, this qualitative analysis showed the presence of SGH-binding IgGs primarily in the sera of exposed group members.

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