Antimicrobial Peptides Show Promise for Combatting Citrus Greening

Citrus greening, or Huanglongbing (HLB), is a disease that devastates citrus production all over the world. The culprit behind HLB is the bacterium Candidatus Liberibacter spp. (e.g., CLas), an unculturable pathogen that has proven very difficult to treat. Once a tree is infected, it becomes unproductive and dies within years, costing the global citrus market billions. While current attempts to combat HLB rely on controlling the insect vector, scientists have turned some attention towards the potential of peptides. Their work displayed how antimicrobial peptides show promise for combatting citrus greening, mainly by methods against CLas itself.

Antimicrobial peptides effective against CLas bacteria

With not many current effective options to fight HLB, scientists believe the next area of area of interest was targeting the CLas secretory pathway using antimicrobial peptides provided by LifeTein. Specifically, the antimicrobial peptides would be blocking the TolC efflux pump protein. The study found three peptides capable of doing this by binding tightly with the TolC receptors, and even the β barrel entrance of the protein as well. Treatment with peptides in this manner showed effective inhibition and even mortality in models closely resembling CLas.

The studies displayed using antimicrobial peptides show major promise for future treatment of HLB. With the chemical resistant bacteria CLas being nearly impossible to slow down, peptides just may have been holding the solution all along. There is hope that new therapies can be developed utilizing the strategies shown, and the global citrus production can rest easy after decades worth of HLB ravaging the farms.

Wang, Haoqi, Nirmitee Mulgaonkar, Samavath Mallawarachchi, Manikandan Ramasamy, Carmen S. Padilla, Sonia Irigoyen, Gitta Coaker, Kranthi K. Mandadi, and Sandun Fernando. 2022. “Evaluation of Candidatus Liberibacter Asiaticus Efflux Pump Inhibition by Antimicrobial Peptides” Molecules 27, no. 24: 8729. https://doi.org/10.3390/molecules27248729

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How does BIRD-2 peptide kill B-cell lymphoma?

The anti-apoptotic factor Bcl-2 is over-expressed in B-cell lymphoma cells as their main survival mechanism by binding to IP3R2 on endoplasmic reticulum (ER).  In this study, a cell-penetrating version of BIRD-2 peptide (Bcl-2/IP3R Disrupter-2 peptide with a TAT sequence) made by LifeTein was used to break up the complex formed by Bcl-2 and IP3R2 in human diffuse large B-cell lymphoma (DLBCL) cells. Ca2+ signaling-related events are suggested to be the killing mechanism of BIRD-2 peptide on DLBCL cells.

Bird-2 Peptides & B-Cell Lymphoma

[PDF] Inhibiting Bcl-2 via its BH4 domain in DLBCL cancers to provoke pro-apoptotic Ca2+ signaling

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LifeTein Launches Rush Custom Peptide Synthesis Service: Peptide Delivered in 3-5 Days

Peptide Synthesis for Cell-penetration Studies

Cell-penetrating peptides (CPPs) have the ability to enter a cell’s plasma membrane independent of a membrane receptor. Attached to a CPP, therapeutic cargo could be delivered to an intracellular target, thus overcoming the entry restrictions set by the plasma membrane.

Peptide Synthesis & Cell Penetration

The cationic CPPs interact with negatively charged head groups of lipids directly in the plasma membrane through electrostatic interactions. The increased local peptide concentration at the membrane surface will cause a transient destabilization of the lipid bilayer and lead to cell entry. The hydrophobic interactions, especially facilitated by the presence of tryptophan residues, may be important for the CPP-membrane interaction and cellular internalization.

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