Ubiquicidin (UBI)/ribosomal protein S30 (RS30) is an intracellular
protein with antimicrobial activities against various pathogens. UBI
(29–41) and UBI (31–38) are two crucial peptides derived
from Ubiquicidin, which have shown potential as infection imaging
probes. Here, we report the interactions of UBI-derived peptides with
anionic and zwitterionic phospholipid membranes. Our isothermal titration
calorimetry results show that both peptides selectively interact with
the anionic phospholipid membrane (a model bacterial membrane) and
reside mainly on the membrane surface. The interaction of UBI-derived
peptides with the anionic phospholipid membrane is exothermic and
driven by both enthalpy (ΔH) and entropy (ΔS), with the entropic term TΔS being greater than ΔH. This large
entropic term can be a result of the aggregation of the anionic vesicles,
which is confirmed by dynamic light scattering (DLS) measurements.
DLS data show that vesicle aggregation is enhanced with increasing
peptide-to-lipid molar ratios (P/L) and is found to be more pronounced
in the case of UBI (29–41). DLS results are found to be consistent
with independent transmission measurements. To study the effects of
UBI-derived peptides on the microscopic dynamics of the model bacterial
membrane, quasielastic neutron scattering (QENS) measurements have
been carried out. The QENS results show that both peptides restrict
the lateral motion of the lipid within the leaflet. UBI (29–41)
acts as a stronger stiffening agent, hindering the lateral diffusion
of lipids more efficiently than UBI (31–38). To our knowledge,
this is the first report illustrating the mechanism of interaction
of UBI-derived peptides with model membranes. This study also has
implications for the improvement and design of antimicrobial peptide-based
infection imaging probes.
Developing potent and novel bacterial imaging agents remains formidable due to the rapid development of bacterial resistance. Ubiquicidin and its derivatives are the most studied antimicrobial peptides that bind to...
The ubiquitous occurrence of Antimicrobial Peptides (AMPs) in all domains of life emphasizes
their crucial role as ancient mediators of host defense. Despite their antiquity and prolonged history
of exposure to pathogens, endogenous AMPs continue to serve as effective antibiotics. An "evolutionary
arms race" between host and pathogen resulted in structural diversity of AMPs, leading these
molecules to retain activity against a wide range of pathogens, including antibiotic-resistant microbes.
As the menace of antibiotic resistance continues to render most antibiotics ineffective against pathogens,
the search for novel drug candidates has taken the center stage. The ability of AMPs to combat
antibiotic-resistant microbes gave rise to a remarkable surge of interest in AMPs as potential therapeutics.
Apart from being effective antimicrobials, AMPs have also found application as probes suitable
for in-situ diagnosis of infection. Here, we review the evolutionary history of AMPs, their structural
diversity, and mechanism of interaction with microbial membranes. We also summarize the role of
AMPs as modern pharmaceuticals and challenges to this development.
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