Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions.
BACKGROUND:On a global scale scabies is one of the most common dermatological conditions, imposing a considerable economic burden on individuals, communities and health systems. There is substantial epidemiological evidence that in tropical regions scabies is often causing pyoderma and subsequently...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2017
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0005437 https://doaj.org/article/eb6c7047c68447a3a86a35daff8ff805 |
id |
ftdoajarticles:oai:doaj.org/article:eb6c7047c68447a3a86a35daff8ff805 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:eb6c7047c68447a3a86a35daff8ff805 2023-05-15T15:15:40+02:00 Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions. Pearl M Swe Lindsay D Christian Hieng C Lu Kadaba S Sriprakash Katja Fischer 2017-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005437 https://doaj.org/article/eb6c7047c68447a3a86a35daff8ff805 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5360341?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005437 https://doaj.org/article/eb6c7047c68447a3a86a35daff8ff805 PLoS Neglected Tropical Diseases, Vol 11, Iss 3, p e0005437 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005437 2022-12-31T09:19:10Z BACKGROUND:On a global scale scabies is one of the most common dermatological conditions, imposing a considerable economic burden on individuals, communities and health systems. There is substantial epidemiological evidence that in tropical regions scabies is often causing pyoderma and subsequently serious illness due to invasion by opportunistic bacteria. The health burden due to complicated scabies causing cellulitis, bacteraemia and sepsis, heart and kidney diseases in resource-poor communities is extreme. Co-infections of group A streptococcus (GAS) and scabies mites is a common phenomenon in the tropics. Both pathogens produce multiple complement inhibitors to overcome the host innate defence. We investigated the relative role of classical (CP), lectin (LP) and alternative pathways (AP) towards a pyodermic GAS isolate 88/30 in the presence of a scabies mite complement inhibitor, SMSB4. METHODOLOGY/PRINCIPAL FINDINGS:Opsonophagocytosis assays in fresh blood showed baseline immunity towards GAS. The role of innate immunity was investigated by deposition of the first complement components of each pathway, specifically C1q, FB and MBL from normal human serum on GAS. C1q deposition was the highest followed by FB deposition while MBL deposition was undetectable, suggesting that CP and AP may be mainly activated by GAS. We confirmed this result using sera depleted of either C1q or FB, and serum deficient in MBL. Recombinant SMSB4 was produced and purified from Pichia pastoris. SMSB4 reduced the baseline immunity against GAS by decreasing the formation of CP- and AP-C3 convertases, subsequently affecting opsonisation and the release of anaphylatoxin. CONCLUSIONS/SIGNIFICANCE:Our results indicate that the complement-inhibitory function of SMSB4 promotes the survival of GAS in vitro and inferably in the microenvironment of the mite-infested skin. Understanding the tripartite interactions between host, parasite and microbial pathogens at a molecular level may serve as a basis to develop improved intervention ... Article in Journal/Newspaper Arctic Mite Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 3 e0005437 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Pearl M Swe Lindsay D Christian Hieng C Lu Kadaba S Sriprakash Katja Fischer Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:On a global scale scabies is one of the most common dermatological conditions, imposing a considerable economic burden on individuals, communities and health systems. There is substantial epidemiological evidence that in tropical regions scabies is often causing pyoderma and subsequently serious illness due to invasion by opportunistic bacteria. The health burden due to complicated scabies causing cellulitis, bacteraemia and sepsis, heart and kidney diseases in resource-poor communities is extreme. Co-infections of group A streptococcus (GAS) and scabies mites is a common phenomenon in the tropics. Both pathogens produce multiple complement inhibitors to overcome the host innate defence. We investigated the relative role of classical (CP), lectin (LP) and alternative pathways (AP) towards a pyodermic GAS isolate 88/30 in the presence of a scabies mite complement inhibitor, SMSB4. METHODOLOGY/PRINCIPAL FINDINGS:Opsonophagocytosis assays in fresh blood showed baseline immunity towards GAS. The role of innate immunity was investigated by deposition of the first complement components of each pathway, specifically C1q, FB and MBL from normal human serum on GAS. C1q deposition was the highest followed by FB deposition while MBL deposition was undetectable, suggesting that CP and AP may be mainly activated by GAS. We confirmed this result using sera depleted of either C1q or FB, and serum deficient in MBL. Recombinant SMSB4 was produced and purified from Pichia pastoris. SMSB4 reduced the baseline immunity against GAS by decreasing the formation of CP- and AP-C3 convertases, subsequently affecting opsonisation and the release of anaphylatoxin. CONCLUSIONS/SIGNIFICANCE:Our results indicate that the complement-inhibitory function of SMSB4 promotes the survival of GAS in vitro and inferably in the microenvironment of the mite-infested skin. Understanding the tripartite interactions between host, parasite and microbial pathogens at a molecular level may serve as a basis to develop improved intervention ... |
format |
Article in Journal/Newspaper |
author |
Pearl M Swe Lindsay D Christian Hieng C Lu Kadaba S Sriprakash Katja Fischer |
author_facet |
Pearl M Swe Lindsay D Christian Hieng C Lu Kadaba S Sriprakash Katja Fischer |
author_sort |
Pearl M Swe |
title |
Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions. |
title_short |
Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions. |
title_full |
Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions. |
title_fullStr |
Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions. |
title_full_unstemmed |
Complement inhibition by Sarcoptes scabiei protects Streptococcus pyogenes - An in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of S. pyogenes to infect mite-induced skin lesions. |
title_sort |
complement inhibition by sarcoptes scabiei protects streptococcus pyogenes - an in vitro study to unravel the molecular mechanisms behind the poorly understood predilection of s. pyogenes to infect mite-induced skin lesions. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0005437 https://doaj.org/article/eb6c7047c68447a3a86a35daff8ff805 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic Mite |
genre_facet |
Arctic Mite |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 3, p e0005437 (2017) |
op_relation |
http://europepmc.org/articles/PMC5360341?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005437 https://doaj.org/article/eb6c7047c68447a3a86a35daff8ff805 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005437 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
11 |
container_issue |
3 |
container_start_page |
e0005437 |
_version_ |
1766346019204759552 |