Proteomic Adaptation of <i>Streptococcus pneumoniae</i> to the Antimicrobial Peptide Human Beta Defensin 3 (hBD3) in Comparison to Other Cell Surface Stresses.
Mücke. Pierre-Alexander PA; Ostrzinski. Anne A; Hammerschmidt. Sven S; Maaß. Sandra S; Becher. Dörte D
Key Findings
- hBD3 and LL-37 produce largely overlapping proteomic responses in Streptococcus pneumoniae
- LL-37 uniquely alters proteins involved in cell‑surface modification, not seen with hBD3
- The detergent CTAB induces distinct protein changes, including activation of a two‑component system also responsive to peptide stress
Practical Outcomes
- The work shows that LL‑37 may provoke specific bacterial resistance mechanisms beyond those triggered by hBD3, hinting that therapies based on LL‑37 could encounter unique adaptation pathways. For biohackers, this is mainly mechanistic insight and doesn’t translate into immediate dosing or usage guidelines.
Summary
Scientists studied how the pneumonia‑causing bacteria change their protein makeup when hit with two human antimicrobial peptides, hBD3 and LL‑37, and a detergent. Both peptides caused similar shifts, but LL‑37 also triggered extra proteins that tweak the bacterial surface, while the detergent caused its own unique changes.
Abstract
The antimicrobial peptide human Beta defensin 3 (hBD3) is an essential part of the innate immune system and is involved in protection against respiratory pathogens by specifically permeabilizing bacterial membranes. The Gram-positive bacterium <i>Streptococcus pneumoniae</i> causes serious diseases including pneumonia, meningitis, and septicemia, despite being frequently exposed to human defense molecules, including hBD3 during colonization and infection. Thus, the question arises how pneumococci adapt to stress caused by antimicrobial peptides. We addressed this subject by analyzing the proteome of <i>S. pneumoniae</i> after treatment with hBD3 and compared our data with the proteomic changes induced by LL-37, another crucial antimicrobial peptide present in the human respiratory tract. As antimicrobial peptides usually cause membrane perturbations, the response to the membrane active cationic detergent cetyltrimethylammonium bromide (CTAB) was examined to assess the specificity of the pneumococcal response to antimicrobial peptides. In brief, hBD3 and LL-37 induce a similar response in pneumococci and especially, changes in proteins with annotated transporter and virulence function have been identified. However, LL-37 causes changes in the abundance of cell surface modification proteins that cannot be observed after treatment with hBD3. Interestingly, CTAB induces unique proteomic changes in <i>S. pneumoniae</i>. Though, the detergent seems to activate a two-component system that is also activated in response to antimicrobial peptide stress (TCS 05). Overall, our data represent a novel resource on pneumococcal adaptation to specific cell surface stresses on a functional level. This knowledge can potentially be used to develop strategies to circumvent pneumococcal resistance to antimicrobial peptides.
Study Information
pubmed
2020
2020-10-30T00:00:00.000Z
10.3390/microorganisms8111697
3
35