IgG Endopeptidase SeMac does not Inhibit Opsonophagocytosis of Streptococcus equi Subspecies equi by Horse Polymorphonuclear Leukocytes.
Abstract: The secreted Mac protein made by group A Streptococcus (GAS) inhibits opsonophagocytosis of GAS by human polymorphonuclear leukocytes (PMNs). This protein also has the endopeptidase activity against human immunoglobulin G (IgG), and the Cys94, His262 and Asp284 are critical for the enzymatic activity. The horse pathogen Streptococcus equi subspecies equi produces a homologue of Mac (SeMac). SeMac was characterized to determine whether SeMac has IgG endopeptidase activity and inhibits opsonophagocytosis of S. equi by horse PMNs. The gene was cloned and recombinant SeMac was overexpressed in Escherichia coli and purified to homogeneity. Mice with experimental S. equi infection and horses with strangles caused by S. equi seroconverted to SeMac, indicating that SeMac is produced in vivo during infection. SeMac has endopeptidase activity against human IgG. However, the protein just cleaves a small fraction, which may be IgG1 only, of horse IgG. Replacement of Cys102 with Ser or His272 with Ala abolishes the enzymatic activity of SeMac, and the Asp294Ala mutation greatly decreases the enzymatic activity. SeMac does not inhibit opsonophagocytosis of S. equi by horse PMNs but opsonophagocytosis of GAS by human PMNs. Thus, SeMac is a cysteine endopeptidase with a limited activity against horse IgG and must have other function.
Publication Date: 2010-04-08 PubMed ID: 20556207PubMed Central: PMC2885601DOI: 10.2174/1874285801004010020Google Scholar: Lookup
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- Journal Article
Summary
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This research investigates whether the SeMac protein, produced by a horse pathogen, possesses endopeptidase activity, and if it can inhibit the process in which horse immune cells (PMNs) swallow and destroy certain bacterial pathogens. They found that SeMac does have this activity against antibodies in humans but has limited effectiveness against horse antibodies. Furthermore, it does not stop horse PMNs from destroying the bacteria.
Study Methods and Findings
- The protein SeMac, produced by the horse pathogen Streptococcus equi, was studied to understand if it has immunoglobulin G (IgG) endopeptidase activity and whether it could inhibit a process called opsonophagocytosis in horse PMNs (a type of immune cell).
- Researchers cloned the gene which codes for SeMac and overexpressed it in E. coli bacteria, effectively producing a large quantity of the protein for study.
- They found that mice and horses infected with S. equi produced antibodies against SeMac, confirming that it is indeed active during infections.
- SeMac demonstrated endopeptidase activity against human IgG, meaning it is capable of breaking down these antibodies. However, it only seemed to break down a small fraction of horse IgG and was less active.
- When important amino acids in SeMac (Cys102 and His272) were replaced, the enzyme lose its ability to break down antibodies, suggesting these parts are crucial for its function.
Implications and Further Findings
- Notably, SeMac did not inhibit the ability of horse PMNs to undergo opsonophagocytosis of S. equi. In fact, SeMac only inhibited opsonophagocytosis of group A Streptococcus (GAS) by human PMNs.
- In other words, while SeMac can break down some human antibodies and potentially interfere with human immune responses to GAS, it was less effective against horse antibodies and did not interfere with the horse immune response to S. equi.
- Given its limited activity against horse IgG and its inability to inhibit horse opsonophagocytosis, researchers suggest that SeMac likely has other functions in the infection process that are not yet understood.
- This finding helps in understanding the precise roles of bacterial proteins in the infection process and may aid future therapeutic strategies against S. equi and similar pathogens.
Cite This Article
APA
Liu M, Lei B.
(2010).
IgG Endopeptidase SeMac does not Inhibit Opsonophagocytosis of Streptococcus equi Subspecies equi by Horse Polymorphonuclear Leukocytes.
Open Microbiol J, 4, 20-25.
https://doi.org/10.2174/1874285801004010020 Publication
Researcher Affiliations
- Department of Veterinary Molecular Biology, Montana State University, Bozeman, Montana 59717, USA.
Grant Funding
- P20 RR020185 / NCRR NIH HHS
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Citations
This article has been cited 1 times.- Lei B. Benfang Lei's research on heme acquisition in Gram-positive pathogens and bacterial pathogenesis.. World J Biol Chem 2010 Sep 26;1(9):286-90.
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