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1. Novel non-helical antimicrobial peptides insert into and fuse lipid model membranes

   https://doi.org/10.1039/D4SM00220B  

   Mitra, Saheli; Chandersekhar, Bhairavi; Li, Yunshu; Coopershlyak, Mark; Mahoney, Margot E; Evans, Brandt; Koenig, Rachel; Hall, Stephen_C L; Klösgen, Beate; Heinrich, Frank; et al (May 2024, Soft Matter)

   Cerbino, Roberto (Ed.)

   This research addresses the growing menace of antibiotic resistance by exploring antimicrobial peptides (AMPs) as alternatives to conventional antibiotics. 

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2. Novel Helical Trp‐ and Arg‐Rich Antimicrobial Peptides Locate Near Membrane Surfaces and Rigidify Lipid Model Membranes

   https://doi.org/10.1002/anbr.202300013  

   Mitra, Saheli; Coopershlyak, Mark; Li, Yunshu; Chandersekhar, Bhairavi; Koenig, Rachel; Chen, Mei-Tung; Evans, Brandt; Heinrich, Frank; Deslouches, Berthony; Tristram-Nagle, Stephanie (April 2023, Advanced NanoBiomed Research)

   Antibiotics are losing effectiveness as bacteria become resistant to conventional drugs. To find new alternatives, antimicrobial peptides (AMPs) are rationally designed with different lengths, charges, hydrophobicities (H), and hydrophobic moments (μH), containing only three types of amino acids: arginine, tryptophan, and valine. Six AMPs with low minimum inhibitory concentrations (MICs) and <25% toxicity to mammalian cells are selected for biophysical studies. Their secondary structures are determined using circular dichroism (CD), which finds that the % α‐helicity of AMPs depends on composition of the lipid model membranes (LMMs): gram‐negative (G(−)) inner membrane (IM) >gram‐positive (G(+))> Euk33 (eukaryotic with 33 mol% cholesterol). The two most effective peptides, E2‐35 (16 amino acid [AA] residues) and E2‐05 (22 AAs), are predominantly helical in G(–) IM and G(+) LMMs. AMP/membrane interactions such as membrane elasticity, chain order parameter, and location of the peptides in the membrane are investigated by low‐angle and wide‐angle X‐ray diffuse scattering (XDS). It is found that headgroup location correlates with efficacy and toxicity. The membrane bending modulusK_Cdisplays nonmonotonic changes due to increasing concentrations of E2‐35 and E2‐05 in G(–) and G(+) LMMs, suggesting a bacterial killing mechanism where domain formation causes ion and water leakage. 

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3. Caerin 1 Antimicrobial Peptides that Inhibit HIV and Neisseria May Spare Protective Lactobacilli

   https://doi.org/10.3390/antibiotics9100661  

   Rollins-Smith, Louise A.; Smith, Patricia B.; Ledeczi, Anna M.; Rowe, Julia M.; Reinert, Laura K. (October 2020, Antibiotics)

   null (Ed.)

   Although acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) is a manageable disease for many, it is still a source of significant morbidity and economic hardship for many others. The predominant mode of transmission of HIV/AIDS is sexual intercourse, and measures to reduce transmission are needed. Previously, we showed that caerin 1 antimicrobial peptides (AMPs) originally derived from Australian amphibians inhibited in vitro transmission of HIV at relatively low concentrations and had low toxicity for T cells and an endocervical cell line. The use of AMPs as part of microbicidal formulations would expose the vaginal microbiome to these agents and cause potential harm to protective lactobacilli. Here, we tested the effects of caerin 1 peptides and their analogs on the viability of two species of common vaginal lactobacilli (Lactobacillus rhamnosus and Lactobacillus crispatus). Several candidate peptides had limited toxicity for the lactobacilli at a range of concentrations that would inhibit HIV. Three AMPs were also tested for their ability to inhibit growth of Neisseria lactamica, a close relative of the sexually transmissible Neisseria gonorrhoeae. Neisseria lactamica was significantly more sensitive to the AMPs than the lactobacilli. Thus, several candidate AMPs have the capacity to inhibit HIV and possible N. gonorrhoeae transmission at concentrations that are significantly less harmful to the resident lactobacilli. 

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4. Synthesis of Lysine Mimicking Membrane Active Antimicrobial Polymers

   Ankita Arora; Wan Zheng; Hongjun Liang; Abhijit Mishra (November 2018, Advances in Polymer Sciences and Technology)

   Bhuvanesh Gupta; Anup K.Ghosh; Atsushi Suzuki; Sunita Rattan (Ed.)

   Antibiotic resistance in bacteria is a major health concern. Antimicrobial Peptides (AMPs) are efficient in killing most microbes and yet the development of resistance to AMPs is rare. Although AMPs show promising antimicrobial activities, commercializing them as antibiotics is difficult as in vitro extraction and purification of AMPs is complicated and expensive. AMP mimicking antimicrobial polymers can overcome such problems while maintaining the necessary features of AMPs. Here, we have developed meth-acrylamide based polymers to mimic AMPs which possess high antimicrobial activities with low cytotoxicity. Bactericidal and scanning electron microscopy studies show that the synthesized polymers are effective against Gram-positive and Gram-negative bacteria. We find that these polymers are lethal to bacteria and at the same time, they are also non-cytotoxic to mammalian cells, thereby increasing the potential of these polymers to be used as antibiotics. 

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5. Single-cell stochastic modelling of the action of antimicrobial peptides on bacteria

   https://doi.org/10.1098/rsif.2021.0392  

   Teimouri, Hamid; Nguyen, Thao N.; Kolomeisky, Anatoly B. (September 2021, Journal of The Royal Society Interface)

   null (Ed.)

   Antimicrobial peptides (AMPs) produced by multi-cellular organisms as their immune system’s defence against microbes are actively considered as natural alternatives to conventional antibiotics. Although substantial progress has been achieved in studying the AMPs, the microscopic mechanisms of their functioning remain not well understood. Here, we develop a new theoretical framework to investigate how the AMPs are able to efficiently neutralize bacteria. In our minimal theoretical model, the most relevant processes, AMPs entering into and the following inhibition of the single bacterial cell, are described stochastically. Using complementary master equations approaches, all relevant features of bacteria clearance dynamics by AMPs, such as the probability of inhibition and the mean times before the clearance, are explicitly evaluated. It is found that both processes, entering and inhibition, are equally important for the efficient functioning of AMPs. Our theoretical method naturally explains a wide spectrum of efficiencies of existing AMPs and their heterogeneity at the single-cell level. Theoretical calculations are also consistent with existing single-cell measurements. Thus, the presented theoretical approach clarifies some microscopic aspects of the action of AMPs on bacteria. 

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