Chlamydial-Secreted Protease Chlamydia High Temperature Requirement Protein A (cHtrA) Degrades Human Cathelicidin LL-37 and Suppresses Its Anti-Chlamydial Activity.
Dong. Xiaohua X; Zhang. Wanxing W; Hou. Jianmei J; Ma. Miaomiao M; Zhu. Congzhong C; Wang. Huiping H; Hou. Shuping S
Key Findings
- LL‑37 is the most potent of five tested antimicrobial peptides against C. trachomatis.
- Chlamydia secretes the protease cHtrA, which specifically degrades LL‑37 and blocks its anti‑chlamydial activity.
- cHtrA mutants (MT‑H143A and MT‑S247A) lose the ability to degrade LL‑37, confirming the enzyme’s role.
Practical Outcomes
- For biohackers considering LL‑37 supplementation to fight infections, this research suggests Chlamydia can neutralize it, so LL‑37 alone may not be effective against this pathogen. Combining LL‑37 with protease inhibitors or targeting cHtrA could be a more viable strategy, but more research is needed before any protocol changes.
Summary
The study shows that the human antimicrobial peptide LL‑37 can kill the sexually transmitted bacteria Chlamydia trachomatis, but the bacteria release an enzyme (cHtrA) that chops up LL‑37, making it ineffective. Mutated versions of the enzyme can't do this, and the effect is the same across several Chlamydia strains.
Abstract
BACKGROUND Chlamydia trachomatis is an obligate intracellular pathogen that can cause severe reproductive tract complications while ascending infection occurs. When spreading from cell to cell in a host, C. trachomatis utilizes various survival strategies to offset host defense mechanisms. One such strategy is to degrade host antimicrobial defense proteins before they can attack the invading C. trachomatis cells. MATERIAL AND METHODS We expressed and purified recombinant chlamydia high temperature requirement protein A (cHtrA) including 2 cHtrA mutants (MT-H143A and MT-S247A), and also extracted endogenous cHtrA. Proteins were identified and their purity evaluated by SDS-PAGE and Western blot. The anti-chlamydial activity and degradation of 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) by cHtrA and 2 cHtrA mutants (MT-H143A and MT-S247A) were tested by immunoassay and Western blot. RESULTS Of the 5 antimicrobial peptides (cathelicidin LL-37, alpha-defensin-1 and -3, and ß-defensin-2 and -4) tested, cathelicidin LL-37 showed the strongest anti-chlamydial activity. Interestingly, cHtrA effectively and specifically degraded LL-37, suppressing its anti-chlamydial activity. The 2 cHtrA mutants (MT-H143A and MT-S247A) were unable to degrade LL-37. Comparison of cHtrA activity from C. trachomatis D, L2, and MoPn strains on LL-37 showed similar responses. CONCLUSIONS cHtrA may contribute to C. trachomatis pathogenicity by clearing the passage of invasion by specific LL-37 degradation.
Study Information
pubmed
2020
2020-07-07T00:00:00.000Z
10.12659/msm.923909