A Spectroscopic Study of the Aggregation State of the Human Antimicrobial Peptide LL-37 in Bacterial versus Host Cell Model Membranes

Biochemistry ◽  
2015 ◽  
Vol 54 (45) ◽  
pp. 6760-6768 ◽  
Author(s):  
Alessio Bonucci ◽  
Elena Caldaroni ◽  
Enrico Balducci ◽  
Rebecca Pogni
Keyword(s):  
Antimicrobial Peptide ◽  
Spectroscopic Study ◽  
Host Cell ◽  
Cell Model ◽  
Model Membranes ◽  
Aggregation State

Primate cathelicidin orthologues display different structures and membrane interactions

2009 ◽  
Vol 417 (3) ◽  
pp. 727-735 ◽  
Author(s):  
Francesca Morgera ◽  
Lisa Vaccari ◽  
Nikolinka Antcheva ◽  
Denis Scaini ◽  
Sabrina Pacor ◽  
...  
Keyword(s):  
Host Cell ◽  
Structural Characteristics ◽  
Attenuated Total Reflection ◽  
Model Membranes ◽  
Helical Conformation ◽  
Bulk Solution ◽  
Free Form ◽  
Outer Cell ◽  
Membrane Interactions ◽  
Aggregation State

The human cathelicidin LL-37 displays both direct antibacterial activities and the capacity to modulate host-cell activities. These depend on structural characteristics that are subject to positive selection for variation, as observed in a previous analysis of the CAMP gene (encoding LL-37) in primates. The altered balance between cationic and anionic residues in different primate orthologues affects intramolecular salt-bridging and influences the stability of the helical conformation and tendency to aggregate in solution of the peptide. In the present study, we have analysed the effects of these structural variations on membrane interactions for human LL-37, rhesus RL-37 and orang-utan LL-37, using several complementary biophysical and biochemical methods. CD and ATR (attenuated total reflection)-FTIR (Fourier-transform IR) spectroscopy on model membranes indicate that RL-37, which is monomeric and unstructured in bulk solution [F-form (free form)], and human LL-37, which is partly structured and probably aggregated [A-form (aggregated form)], bind biological membranes in different manners. RL-37 may insert more deeply into the lipid bilayer than LL-37, which remains aggregated. AFM (atomic force microscopy) performed on the same supported bilayer as used for ATR-FTIR measurements suggests a carpet-like mode of permeabilization for RL37 and formation of more defined worm-holes for LL-37. Comparison of data from the biological activity on bacterial cells with permeabilization of model membranes indicates that the structure/aggregation state also affects the trajectory of the peptides from bulk solution through the outer cell-wall layers to the membrane. The results of the present study suggest that F-form cathelicidin orthologues may have evolved to have primarily a direct antimicrobial defensive capacity, whereas the A-forms have somewhat sacrificed this to gain host-cell modulating functions.

Mechanisms of a Small Membrane-Active Antimicrobial Peptide from Hyla punctata

2020 ◽  
Vol 73 (3) ◽  
pp. 236 ◽  
Author(s):  
Charles H. Chen ◽  
Jakob P. Ulmschneider ◽  
Martin B. Ulmschneider
Keyword(s):  
Antimicrobial Peptide ◽  
Cell Model ◽  
Dynamic Structure ◽  
Md Simulations ◽  
Model Membranes ◽  
Membrane Thickness ◽  
Oligomeric Structure ◽  
The Past ◽  
Membrane Rigidity ◽  
Bacterial Model

Thousands of antimicrobial peptides have been observed and studied in the past decades; however, their membrane-active mechanisms are ambiguous due to their dynamic structure in the cell membrane. Here, we applied both molecular dynamics (MD) simulations and biophysical experiments to study the small membrane-active antimicrobial peptide Hylaseptin P1 (HSP1), which has significant selectivity towards anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (POPG) and bacterial model membranes. HSP1 does not bind and fold onto human red blood cell model membranes, and it only binds, but does not fold, in zwitterionic 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) membranes. This suggests that the lipid chemistry and membrane rigidity are key to prevent HSP1 binding onto membranes, and the lipid headgroup charge may further promote peptide folding in the membrane. Our experiment-validated MD simulations suggest a carpet-like model mechanism for HSP1 through peptide binding, folding, aggregation, and assembly. HSP1 is shorter than the membrane thickness; therefore, the folded peptides aggregate on the surface, cross the membrane, and the oligomeric structure is supported by several surface-bound peptides in both bilayer leaflets.

Changes in host cell membrane activities in response to adhesion of Neisseria gonorrhoeae

1986 ◽  
Vol 32 (2) ◽  
pp. 83-88 ◽  
Author(s):  
G. M. Wiseman ◽  
C. F. Martin
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Host Cell ◽  
Pyruvate Kinase ◽  
Bacterial Adhesion ◽  
Hypochlorous Acid ◽  
Cell Model ◽  
Anion Transport ◽  
Polymorphonuclear Neutrophils ◽  
Host Cell Membrane ◽  
Isogenic Strains

Physiological changes in host cell model membranes (intact human erythrocytes and ghosts) as a consequence of bacterial adhesion were studied with special reference to Neisseria gonorrhoeae. Membrane activities examined were transport of K+, Cl− ions, pyruvate kinase, Na–K-dependent ATPase, and cAMP. We found that K+ and Cl− transport were affected, more so in membranes with attached pilated (P+) organisms than in those with apilated (P−) isogenic strains. In N. gonorrhoeae and in several other species of gram-negative bacteria studied, hemagglutination titres were directly correlated with effects on anion transport, suggesting that perturbations in anion transport are an immediate result of adhesion. Of three P+ gonococcus strains tested, two depressed Na–K–ATPase activity in the membrane, indicating a possible effect on the Na–K pump. Pyruvate kinase activity associated with the membrane appeared to be stimulated by attached gonococci, again by P+ strains to higher levels than P− organisms. Clearly, some enzyme properties of host membranes are intrinsically affected by bacterial adhesion. Human polymorphonuclear neutrophils were also investigated, and with some exceptions, changes observed in leukocyte enzyme activities tended to parallel those in erythrocytes. Since hypochlorous acid production is considered to be an important microbicidal mechanism in neutrophils, interference with Cl− transport could jeopardize their role in host defense.

Proteases of Sporothrix schenckii : Cytopathological effects on a host-cell model

2018 ◽  
Vol 35 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Myrna Sabanero López ◽  
Lérida L. Flores Villavicencio ◽  
Karla Soto Arredondo ◽  
Gloria Barbosa Sabanero ◽  
Julio César Villagómez-Castro ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Model ◽  
Sporothrix Schenckii

scholarly journals Dual functions of the human antimicrobial peptide LL-37—Target membrane perturbation and host cell cargo delivery

2010 ◽  
Vol 1798 (12) ◽  
pp. 2201-2208 ◽  
Author(s):  
Xuan Zhang ◽  
Kamila Oglęcka ◽  
Staffan Sandgren ◽  
Mattias Belting ◽  
Elin K. Esbjörner ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Host Cell ◽  
Membrane Perturbation ◽  
Cargo Delivery ◽  
Target Membrane ◽  
Dual Functions
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