Antimicrobial Peptides

Peptide microarrays are to proteomics as sequencing is to genomics. As microarrays become more content-rich, higher resolution proteomic studies will parallel deep sequencing of nucleic acids. Antigen-antibody interactions can be studied at a much higher resolution using microarrays than was possible only a decade ago. My dissertation focuses on testing the feasibility of using either the Immunosignature platform, based on non-natural peptide sequences, or a pathogen peptide microarray, which uses bioinformatically-selected peptides from pathogens for creating sensitive diagnostics. Both diagnostic applications use relatively little serum from infected individuals, but each approaches diagnosis of disease differently. The first project compares pathogen epitope
peptide (life-space) and non-natural (random-space) peptide microarrays while using them for the early detection of Coccidioidomycosis (Valley Fever). The second project
uses NIAID category A, B and C priority pathogen epitope peptides in a multiplexed microarray platform to assess the feasibility of using epitope peptides to simultaneously diagnose multiple exposures using a single assay. Cross-reactivity is a consistent feature of several antigen-antibody based immunodiagnostics. This work utilizes microarray optimization and bioinformatic approaches to distill the underlying disease specific antibody signature pattern. Circumventing inherent cross-reactivity observed in antibody binding to peptides was crucial to achieve the goal of this work to accurately distinguishing multiple exposures simultaneously.

“Global Peptide Antibiotics Market and Clinical Pipeline Insight 2023” report gives comprehensive insight on clinical and non-clinical parameters involved in the development and commercialization of global peptide antibiotics market. As per report findings, peptide antibiotics are expected to emerge as new growth frontier for the various stake holders involved in the research and development of antibiotics. Currently, there are 6 peptide antibiotics commercially available in the market and 24 peptide antibiotics are in clinical pipeline. With the era of “classical antibiotics” coming to an end with problems like heavy resistance to conventional antibiotics, the new era of peptide antibiotics is on its way to revolutionize the antibiotics segment. The peptide antibiotics are at the apex of new generation medications which are sure to storm the markets in the coming years.

The number of nosocomial infections related to
implants and medical devices increase alarmingly worldwide.
New strategies based on the design of antimicrobial coatings
are required to prevent such infections. Polyelectrolyte
“multilayer” films constitute a powerful tool for nanoscale
surface functionalization which allows addressing this issue. By
investigating films built up with poly(arginine) (PAR) of
various chain lengths (10, 30, 100, and 200 residues) and
hyaluronic acid (HA), we demonstrate that exclusively films
constructed with poly(arginine) composed of 30 residues
(PAR30) acquire a strong antimicrobial activity against Gram-
positive and Gram-negative pathogenic bacteria associated
with infections of medical devices. This chain-size effect is extremely striking and is the first example reported where the length of
the polyelectrolytes played a key-role in the functionality of the films. Moreover, this unexpected functionality of nanolayered
polypeptide/polysaccharide PAR30/HA films occurs without adding any specific antimicrobial agent, such as antibiotics or
antimicrobial peptides. PAR30/HA film inhibits bacteria through a contact-killing mechanism due to the presence of mobile
PAR30 chains. These chains are assumed to diffuse toward the interface, where they interact with the bacteria with the consequence of killing them. This new coating with unique properties based on the association of a homopolypeptide of 30 residues with a polysaccharide constitutes a simple system to prevent implant-related infections with a reasonable production cost.

Antimicrobial peptides (AMPs) are components of
the innate immune system in many species of animals. Their
diverse spectrum of activity against microbial pathogens, both
as innate defense molecules and immunomodulators, makes
them attractive candidates for the development of a new generation
of antibiotics. Although the potential immunogenicity
of AMPs means they are not suitable for injection and their
susceptibility to digestive peptidases is likely to reduce their
oral efficacy, they are ideal for topical formulations such as
lotions, creams, shampoos, and wound dressings and could
therefore be valuable products for the cosmetic industry. In
this context, short AMPs (<20 amino acids) lacking disulfide
bonds combine optimal antimicrobial activity with inexpensive
chemical synthesis and are therefore more compatible
with large-scale production and the modifications required to
ensure stability, low toxicity, and microbial specificity. Proofof-
concept for the application of AMPs as novel antiinfectives
has already been provided in clinical trials. This
perspective considers the anti-infective properties of short
AMPs lacking disulfide bonds, which are active against
dermatologically important microflora. We consider the challenges
that need to be addressed to facilitate the prophylactic
application of AMPs in personal care products.

The antimicrobial activity of different solvent extracts (hydro alcoholic extracts of methanol) of different parts of Lagenaria siceraria (Molina) Standl was evaluated for its antimicrobial potential.  The in vitro antimicrobial activity was evaluated by agar well diffusion method. Extraction was done by individual cold percolation method. The antimicrobial activity was tested against five Gram positive bacteria, five Gram negative bacteria and four fungi.  The MIC and MBC was also determined, including five antibiotics. All the parts possessed antimicrobial activity but to a different level.  The extracts showed better antifungal activity than antibacterial activity and Gram negative bacteria were more susceptible than Gram positive bacteria. The peel showed lowest MIC and MBC values indicating the therapeutic value of agro waste material.

Antimicrobial peptides (AMPs) are showing increasing promise as potential candidate antibacterial drugs in the face of the rapidly emerging bacterial resistance to conventional antibiotics in recent years. The target of these peptides is the microbial membrane and there are numerous models to explain their mechanism of action ranging from pore formation to general membrane disruption. The interaction between the AMP and the target membrane is critical to the specificity and activity of these peptides. However, a precise understanding of the relationship between antimicrobial peptide structure and their cytolytic function in a range of organisms is still lacking. This is a result of the complex nature of the interactions of AMPs with the cell membrane, the mechanism of which can vary considerably between different classes of antimicrobia peptides. A wide range of biophysical techniques have been used to study the influence of a number of peptide and membrane properties on the cytolytic activity of these peptides in model membrane systems. Central to characterisation of this interaction is a quantitative analysis of the binding of peptide to the membrane and the coherent dynamic changes in membrane structure. Recently, dual polarization interferometry has been used to perform an in depth analysis of antimicrobial peptide induced membrane perturbation and with new mass-structure co-fitting kinetic analysis have allowed a real-time label free analysis of binding affinity and kinetics. We review these studies which describe multi-step mechanisms which are adopted by various AMPs in nature and may advance our approach to the development of a new generation of effective antimicrobial therapeutics.

Antibiotics  provide  the  main  basis  for  the  therapy  of microbial  (bacterial  and
fungal)  infections.  Since  the  discovery  of  these  antibiotics  and  their  uses  as
chemotherapeutic  agents  there  was  a  belief  in  the  medical  fraternity  that  this
would  lead  to  the  eventual  eradication  of  infectious  diseases.  There  is  a
continuous  and  urgent  need  to  discover  new  antimicrobial  compounds  with
diverse  chemical  structures  and  novel  mechanisms  of  action  because  there  has
been  an  alarming  increase  in  the  incidence  of  new  and  re-emerging  infectious
diseases. Another big concern is the development of resistance to the antibiotics
in  current  clinical  use.  In  recent  years,  drug  resistance  to  human  pathogenic
bacteria  has  been  commonly  reported  from  all  over  the  world.  In  the  present
scenario  of  emergence  of  multiple  drug  resistance  to  human  pathogenic
organisms, this has necessitated a search for new antimicrobial substances from
other  sources  including  plants.  Higher  plants  produce  hundreds  to  thousands  of
diverse  chemical  compounds  with  different  biological  activities.  The
antimicrobial compounds produced by plants are active against plant and human
pathogenic microorganisms. It is expected that plant extracts showing target sites
other than those used by antibiotics will be active against drug-resistant microbial
pathogens.

A  new  and  novel  approach  for  the  green  synthesis  of  silver
nanoparticles  is  the  need  of  the  hour.  Use  of  plant  parts  for  the
synthesis of silver nanoparticles is ecofriendly, economic and cost
effective. In the present paper, silver nanoparticles were synthesized
using  aqueous  stem  extract  of Cassia  roxburghii DC  as  a  reducing
agent.  The  biosynthesized  AgNPs  were  characterized  by  various
spectral analysis like UV–Vis, FTIR, XRD, TEM and Zeta potential
measurement. UV–vis spectra showed maxima absorption peak at
432  nm.  XRD  and  TEM  analysis  revealed  AgNPs  to  be  facecentered, cubic structures spherical in shape with an average particle
size of 32-35 nm.
The synergistic antibacterial activity was evaluated against two Gram
positive,  two  Gram  negative  bacteria  and  four  fungi  with  fifteen
commercial antibiotics alone and antibiotics plus synthesized AgNPs.
Antioxidant  activity  of  AgNPs  was  evaluated  by  ABTS  and  FRAP
assay.  The  AgNPs  showed  synergistic  antibacterial  activity  even
better than some antibiotics and also good  antioxidant activity. The
results suggest that Cassia roxburghii stem could be exploited for the
fabrication  of  AgNPs  with  potential  therapeutic  application  in
nanomedicine especially against multi drug resistant microorganisms
which  are  cost  effective  and  ecofriendly  and  simple.  They  can  be
definitely used in cosmetics, medical and pharmaceutical applications

En el capítulo 10 “Metabolismo y formación de biopelícula en Staphylococcus aureus”, de Liliana Muñoz Molina, Cristian Alexander Castillo Sánchez, Laura Camila Viuche Malaver, Angie Carolina Sierra Vargas, Cristian Alejandro Ricaurte Pérez, Jeannette Navarrete Ospina y Gladys Pinilla Bermúdez, el Staphylococcus aureus es un microorganismo patógeno y comensal, causante de infecciones de piel, del tracto urinario, de las vías gastrointestinales, endocarditis, septicemia, contaminación de heridas quirúrgicas y de dispositivos médicos permanentes. Presenta una resistencia parcial o total al efecto de algunos antibióticos, fenómeno que implica una participación activa de todos los factores de virulencia de la bacteria para su efectiva colonización e infección; causa aumento en la tasa de mortalidad y morbilidad, así como en los costos, por incremento en las estancias hospitalarias, situación que se ha convertido en una amenaza para la salud pública.

Bacteria predominantly exist as multicellular aggregates known as biofilms that are associated with at least two thirds of all infections and exhibit increased adaptive resistance to conventional antibiotic therapies. Therefore, biofilms are major contributors to the global health problem of antibiotic resistance, and novel approaches to counter them are urgently needed. Small molecules of the innate immune system called host defense peptides (HDPs) have emerged as promising templates for the design of potent, broad-spectrum antibiofilm agents. Here, we review recent developments in the new field of synthetic antibiofilm peptides, including mechanistic insights, synergistic interactions with available antibiotics, and their potential as novel antimicrobials against persistent infections caused by biofilms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.

Objective: The present study aimed to the isolation and
characterization of phytochemicals from tissue cultures of Arnebia
hispidissima. The isolated compounds were evaluated for their
antioxidant and antimicrobial activities.
Materials and Methods: Six derivatives of alkannin and shikonin
were isolated and characterized by using various physical and
spectroscopic techniques from callus tissue of A. hispidissima. The
callus tissue was generated by using Murashige and Skoog culture
medium. The isolated compounds were assayed for DPPH-radical,
reducing power, superoxide anion and metal chelating scavenging
and antimicrobial activities by adopting well established methods.
Results: The observed results revealed that deoxyshikonin showed
maximum inhibition (290.20±0.440%) to DPPH-radical scavenging
assay and shikonin demonstrated higher reducing ability
(498.32±0.431%). Similarly, the propionylalkannin and
acetylshikonin possessed moderate to maximum superoxide
(345.45±0.632%) and metal chelating abilities (264.76±0,531%).
Moreover, effective antimicrobial activity was also demonstrated by
all the isolated derivatives of alkannin and shikonin.
Conclusion: The results of present study suggested that the isolated
compounds demonstrated modern antioxidant and high antimicrobial
activities. Therefore, further investigations need to be carried out to
isolate new phytochemicals from tissues cultures and screening for
other different biological and pharmacological activities.

Objectives: To investigate the phytoconstituents of  D. scandens  and
evaluate its activity against potential wound pathogens  to validate its
uses.
Materials and methods: Antibacterial and antifungal activity of the
root  extracts  against  bacterial  strains  and  one  clinically  important
yeast  strain  was  assessed  using  the  agar  diffusion  assay,  minimum
inhibitory concentration  studies  and their effect was compared with
some  standard  antibiotics.  The  presence  of  major  phytoconstituents
was detected qualitatively and quantitatively.
Results:  Aqueous  ethanol  and  crude  alkaloid  extracts  showed
maximum inhibition of 37.5% and 33.13% and a minimum inhibitory
concentration  of  100  µg/ml  and  <  10  µg/ml  against Streptococcus
mutans and  Proteus  mirabilis,  respectively.  Most  of  the  test
pathogens,  except  P.  mirabilis,  were  found  to  be  susceptible  to  the
two standard antibacterial and two standard antifungal drugs assayed.
The phytochemicals detected included alkaloids, cardiac glycosides,
tannins and terpenoids. Phytochemical analysis showed the presence
of ~ 5% alkaloids.
Conclusion:  The  results  indicated  that  the  D.  scandens possesses
potential  broad-spectrum  antimicrobial  properties  and  the
phytochemicals detected correlate well with the ethnomedicinal uses
and hence require detailed phytochemical investigation for potential
pharmaceutical applications.

Plaque-related diseases, dental caries and periodontal diseases are among the most important preventable global infectious diseases. In addition to mechanical plaque removal nowadays the phytomedicine use is gaining attention throughout the world. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found to have antimicrobial properties. The phytomedicine, today, symbolize safety, in contrast to the synthetics that are regarded as unsafe to humans and the environment. Plant extracts have been used in dentistry for reducing inflammation, as antiplaque agents, for preventing release of histamine and as antiseptics, antioxidants, antimicrobials, antifungals, antibacterials, antivirals and analgesics. The aim of this paper is to consider the resurgence of phytomedicine use in Dentistry.

Goat whey hydrolysates were produced from goat whey using Alcalase® from Bacillus licheniformis. The
goat whey hydrolysate (GWH) with the highest degree of hydrolysis was fractionated by size exclusion
chromatography (SEC), and the antibacterial activity of the GWH and the obtained SEC-fractions were
evaluated using the disc diffusion method. The results showed that the GWH exhibited significantly
higher antibacterial activity than the unhydrolysed goat whey. Among all SEC fractions obtained, only
SEC-F2 and SEC-F3 showed antibacterial activity against the tested bacteria. SEC-F3 exhibited the highest
antibacterial effectiveness against Escherichia coli and Bacillus cereus with MIC values of 0.09 and
0.03 mg/mL respectively, whereas, SEC-F3 and SEC-F2 had comparable MIC values against Staphylococcus
aureus (~0.02 mg/mL). Transmission electron microscopy showed that the GWH caused changes in the
bacterial cells affected. Additionally, LCeMS analysis was used to characterize the peptides of GWH and
SEC-F3. Two major peptides were detected in GWH and SEC-F3, with higher concentration in the latter,
having masses of 730 and 1183 Da, respectively. These results suggest that hydrolysis of goat whey by
Alcalase is an easy tool to enhance its antibacterial activities. GWH and its effective antibacterial fractions
may be used to control the undesirable bacteria in food and improve its safety.

Life-threatening infectious diseases are on their way to cause a worldwide crisis, as treating them effectively is becoming increasingly difficult due to the emergence of antibiotic resistant strains. Antimicrobial peptides (AMPs) form an ancient type of innate immunity found universally in all living organisms, providing a principal first-line of defense against the invading pathogens. The unique diverse function and architecture of AMPs has attracted considerable attention by scientists, both in terms of understanding the basic biology of the innate immune system, and as a tool in the design of molecular templates for new anti-infective drugs. AMPs are gene-encoded short (<100 amino acids), amphipathic molecules with hydrophobic and cationic amino acids arranged spatially, which exhibit broad spectrum antimicrobial activity. AMPs have been the subject of natural evolution, as have the microbes, for hundreds of millions of years. Despite this long history of co-evolution, AMPs have not lost their ability to kill or inhibit the microbes totally, nor have the microbes learnt to avoid the lethal punch of AMPs. AMPs therefore have potential to provide an important breakthrough and form the basis for a new class of antibiotics. In this review, we would like to give an overview of cationic antimicrobial peptides, origin, structure, functions, and mode of action of AMPs, which are highly expressed and found in humans, as well as a brief discussion about widely abundant, well characterized AMPs in mammals, in addition to pharmaceutical aspects and the additional functions of AMPs.


Read More: http://informahealthcare.com/doi/abs/10.3109/07388551.2011.594423

Recently, research into the development of new antimicrobial agents has been driven by the increase in resistance to traditional antibiotics and Emerging Infectious Diseases. Antimicrobial peptides (AMPs) are promising candidates as alternatives to current antibiotics in the treatment and prevention of microbial infections. AMPs are produced by all known living species, displaying direct antimicrobial killing activity and playing an important role in innate immunity. To date, more than 2000 AMPs have been discovered and many of these exhibit broad-spectrum antibacterial, antiviral and anti-parasitic activity. Neglected tropical diseases (NTDs) are caused by a variety of pathogens and are particularly widespread in low-income and developing regions of the world. Alternative, cost effective treatments are desperately needed to effectively battle these medically diverse diseases. AMPs have been shown to be effective against a variety of NTDs, including African trypanosomes, leishmaniosis and Chagas disease, trachoma and leprosy. In this review, the potential of selected AMPs to successfully treat a variety of NTD infections will be critically evaluated.

Peptide-membrane interactions play an important role in a number of biological pro- cesses, such as antimicrobial defence mechanisms, viral translocation, membrane fu- sion and functions of membrane proteins. In particular, amphipathic α-helical peptides comprise a large family of membrane-active peptides that could exhibit a broad range of biological activities. A membrane, interacting with an amphipathic α-helical pep- tide, may experience a number of possible structural transitions, including stretching, reorganization of lipid molecules, formation of defects, transient and stable pores, for- mation of vesicles, endo- and pinocytosis and other phenomena. Naturally, theoretical and experimental studies of these interactions have been an intense on-going area of research. However, complete understanding of the relationship between the structure of the peptide and the mechanism of interaction it induces, as well as molecular details of this process, still remain elusive. Lack of this knowledge is a key challenge in our efforts to elucidate some of the biological functions of membrane active peptides or to design peptides with tailored functionalities that can be exploited in drug delivery or antimicrobial strategies.

In principle, molecular dynamics is a powerful research tool to study peptide-membrane interactions, which can provide a detailed description of these processes on molecular level. However, a model operating on the appropriate time and length scale is imperative in this description. In this study, we adopt a coarse-grained approach where the accessible simulation time and length scales reach microseconds and tens of nanome- ters, respectively. Thus, the two key objectives of this study are to validate the ap- plicability of the adopted coarse-grained approach to the study of peptide-membrane interactions and to provide a systematic description of these interactions as a function of peptide structure and surface chemistry.

We applied the adopted strategy to a range of peptide systems, whose behaviour has been well established in either experiments or detailed atomistic simulations and outlined the scope and applicability of the coarse-grained model. We generated some useful insights on the relationship between the structure of the peptides and the mechanism of peptide-membrane interactions. Particularly interesting results have been obtained for LS3, a membrane spanning peptide, with a propensity to self-assembly into ion-conducting channels. Firstly, we captured, for the first time, the complete process of self-assembly of LS3 into a hexameric ion-conducting channel and explored its properties. The channel has structure of a barrel-stave pore with peptides aligned along the lipid tails. However, we discovered that a shorter version of the peptide leads to a more disordered, less stable structure often classified as a toroidal pore. This link between two types of pores has been established for the first time and opens interesting opportunities in tuning peptide structures for a particular pore-inducing mechanism. We also established that different classes of peptides can be uniquely characterized by the distinct energy profile as they cross the membrane. Finally, we extended this investigation to the internalization mechanisms of more complex entities such as peptide complexes and nanoparticles. Coarse-grained steered molecular dynamics simulations of these model systems are performed and some preliminary results are presented in this thesis.

To summarize, in this thesis, we demonstrate that coarse-grained models can be successfully used to underpin peptide interaction and self-assembly processes in the pres- ence of membranes in their full complexity. We believe that these simulations can be used to guide the design of peptides with tailored functionalities for applications such as drug delivery vectors and antimicrobial systems. This study also suggests that coarse-grained simulations can be used as an efficient way to generate initial configurations for more detailed atomistic simulations. These multiscale simulation ideas will be a natural future extension of this work.

The antibiotic resistance among gram-positive and gram-negative pathogenic bacteria is of global health concern. This has prompted the development of new effective drugs. But the discovery and development of new drugs is slow, and the emergence of resistance to such new drugs, on the other hand, is rapid as well as continuous among the bacteria. Therefore, in tackling the emergence of antibiotic resistant pathogenic bacteria finding alternative ways is vital. This communication, based on the published scientific data, summarizes the antibacterial capacity of some naturally derived agents such as honey, phytocomponents, probiotics, and antimicrobial peptides that might bring new essence in biomedicine.

In order to survive microbe encounters, insects rely on both physical barriers as well as local and systemic immune responses. Most research focusses on adult or larval defenses however, whereas insect eggs are also in need of protection. Lately, the defense of eggs against microbes has received an increasing amount of attention, be it through endogenous egg defenses, trans-generational immune priming (TGIP) or parental investment. Here we studied the endogenous immune response in eggs and adults of Tenebrio molitor. We show that many immune genes are induced in both adults and eggs. Furthermore, we show that eggs reach comparable levels of immune gene expression as adults. These findings show that the eggs of Tenebrio are capable of an impressive endogenous immune response, and indicate that such inducible egg defenses are likely common in insects.

Temporin-1Tl (TL) is a 13-residue frog antimicrobial peptide (AMP) exhibiting potent antimicrobial and anti-inflammatory activity. To develop novel AMP with improved anti-inflammatory activity and antimicrobial selectivity, we designed and synthesized a series of TL analogs by substituting Trp, Arg and Lys at selected positions. Except for Escherichia coli and Staphylococcus epidermidis, all TL analogs exhibited retained or increased antimicrobial activity against seven bacterial strains including three methicillin-resistant Staphylococcus aureus strains compared with TL. TL-1 and TL-4 showed a little increase in antimicrobial selectivity, while TL-2 and TL-3 displayed slightly decreased antimicrobial selectivity because of their about twofold increased hemolytic activity. All TL analogs demonstrated greatly increased anti-inflammatory activity, evident by their higher inhibition of the production tumor necrosis factor-α (TNF-α) and nitric oxide and the mRNA expression of inducible nitric oxide synthase and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells, compared with TL. Taken together, the peptide anti-inflammatory activity is as follows: TL-2 ≈ TL-3 ≈ TL-4 > TL-1 > TL. In addition, LPS binding ability of the peptides corresponded with their anti-inflammatory activity. These results apparently suggest that the anti-inflammatory activity of TL analogs is associated with the direct binding ability between these peptides and LPS. Collectively, our designed TL analogs possess improved anti-inflammatory activity and retain antimicrobial activity without a significant increase in hemolysis. Therefore, it is evident that our TL analogs constitute promising candidates for the development of peptide therapeutics for gram-negative bacterial infection.

Naturally occurring antimicrobial peptides (AMPs) present several drawbacks that strongly limit their development into therapeutically valuable antibiotics. These include susceptibility to protease degradation and high costs of manufacture. To overcome these problems, researchers have tried to develop mimics or peptidomimetics endowed with better properties, while retaining the basic features of membrane-active natural AMPs such as cationic charge and amphipathic design. Protein epitope mimetics, multimeric (dendrimeric) peptides, oligoacyllysines, ceragenins, synthetic lipidated peptides, peptoids and other foldamers are some of the routes explored so far. The synthetic approach has led to compounds that have already entered clinical evaluation for the treatment of specific conditions, such as Staphylococcus (MRSA) infections. Should these trials be successful, an important proof-of-concept would be established, showing that synthetic oligomers rather than naturally occurring molecules could bring peptide-based antibiotics to clinical practice and the drug market for local and systemic treatment of medical conditions associated with multi-drug resistant pathogens.

Biofilms form a complex layer with defined structures, that attach on biotic or abiotic surfaces, are tough to eradicate and tend to cause some resistance against most antibiotics. Several studies confirmed that biofilm-producing bacteria exhibit higher resistance compared to the planktonic form of the same species. Antibiotic resistance factors are well understood in planktonic bacteria which is not so in case of biofilm producing forms. This may be due to the lack of available drugs with known resistance mechanisms for biofilms. Existing antibiotics cannot eradicate most biofilms, especially of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Insects produce complex and diverse set of chemicals for survival and defense. Antimicrobial peptides (AMPs), produced by most insects, generally have a broad spectrum of activity and the potential to bypass the resistance mechanisms of classical antibiotics. Besides, AMPs may well act synergistically with classical antibiotics for a double-pronged attack on infections. Thus, AMPs could be promising alternatives to overcome medically important biofilms, decrease the possibility of acquired resistance and treatment of multidrug-resistant pathogens including ESKAPE. The present review focuses on insect-derived AMPs with special reference to anti-biofilm-based strategies. It covers the AMP composition, pathways and mechanisms of action, the formation of biofilms, impact of biofilms on human diseases, current strategies as well as therapeutic options to combat biofilm with antimicrobial peptides from insects. In addition, the review also illustrates the importance of bioinformatics tools and molecular docking studies to boost the importance of select bioactive peptides those can be developed as drugs, as well as suggestions for further basic and clinical research.

Defensins are one the largest group of antimicrobial peptides and are part of the innate defence. Defensins are produced by animals, plants and fungi. In animals and plants, defensins can be constitutively or differentially expressed both locally or systemically which confer defence before and a stronger response after infection. Immune signalling pathways regulate the gene expression of defensins. These pathways include cellular receptors , which recognise pathogen-associated molecular patterns and are found both in plants and animals. After recognition, signalling pathways and, subsequently, transcriptional factors are activated. There is an increasing number of novel functions in defensins, such as immunomodulators and immune cell attractors. Identification of defensin triggers could help us to elucidate other new functions. The present article reviews the different elicitors of defensins with a main focus on human, fish and marine invertebrate defensins.

Lipopeptide antibiotics represent an old class of antibiotics that were discovered over 50 years ago, which includes the old polymyxins but also new entries, such as the recently approved daptomycin. They generally consist of a hydrophilic cyclic peptide portion attached to a fatty acid chain which facilitates insertion into the lipid bilayer of bacterial membranes. This review presents an overview of this
class of antibiotics, focusing on their therapeutic applications and putting particular emphasis on chemical modifications introduced to improve their activity.

BMAP-27 and melittin are two antimicrobial
peptides (AMPs) that display potent antimicrobial activities
against a wide range of microbes including multidrug
resistant (MDR) strains of bacteria. Unfortunately, their
significant toxicity against eukaryotic cells has hampered
their development into clinically useful antibiotics. In this
study, we have rationally designed a novel hybrid AMP
aiming to retain the potent antimicrobial activities of
BMAP-27 and melittin while enhancing their therapeutic
index. The strategy employed in our design was based on
combining the activities of individual a-helical fragments of
each AMP to generate a novel hybrid AMP with improved
characteristics compared to the parent peptides. Named as
BMAP27-Melittin, the novel peptide displayed broad
spectrum antimicrobial activity against standard
representative Gram-positive and Gram-negative bacterial
strains in the range of 1–7.5 lM. Moreover, the peptide
managed to kill standard resistant strains of MDR bacteria
with significant potency and with MIC values as low as
1 lM. BMAP27-Melittin also proved to exhibit potent antibiofilm
activities while the hemolytic and antiproliferative
studies against eukaryotic cells revealed that the peptide is
exhibiting minimal toxicity at antimicrobial concentrations.
Additionally, the molecular dynamics simulations of the
peptide folding displayed that the hybrid peptide has folded
into a well-defined a-helical structure; supporting the
experimental findings. Overall, this work highlights the
potential of rational design in generating improved AMPs
with enhanced specificity that could be developed into successful therapeutics for the treatment of bacterial infections

Some newly heterochelates synthesized by reflux of 3-acetyl 4-hydroxy coumarin, Enrofloxacin and transition metal. 1H, 13C, IR and ESI Mass confirm the formation of ligand. The heterochelates were characterized on the basis of different spectroscopic techniques like IR studies and elemental analysis while the geometry of complexes was octahedral which is confirmed by electronic spectra analysis. The compounds were subjected to antimicrobial, antioxidant and anti-tubercular activity viewing using serial broth dilution method and Minimum Inhibitory Concentration (MIC) is determined.

Antimicrobial peptides (AMPs) are promising templates for the development of novel antibiofilm drugs. Despite the large number of studies on screening and optimization of AMPs, only a few of these evaluated the antibiofilm activity in physiologically relevant model systems. Potent in vitro activity of AMPs often does not translate into in vivo effectiveness due to the interference of the host microenvironment with
peptide stability/availability. Hence, mimicking the complex environment found in biofilm-associated infections is essential to predict the clinical potential of novel AMP-based antimicrobials. In the present study, we examined the antibiofilm activity of the semisynthetic peptide lin-SB056-1 and its dendrimeric derivative (lin-SB056-1)2-K against Pseudomonas aeruginosa in an in vivo-like three-dimensional (3-D) lung epithelial cell
model and an in vitro wound model (consisting of an artificial dermis and blood components at physiological levels). Although moderately active when tested alone, lin-SB056-1 was effective in reducing P. aeruginosa biofilm formation in association with 3-D lung epithelial cells in combination with the chelating agent EDTA. The dimeric derivative (lin-SB056-1)2-K demonstrated an enhanced biofilm-inhibitory activity as
compared to both lin-SB056-1 and the lin-SB056-1/EDTA combination, reducing the number of biofilm-associated bacteria up to 3-Log units at concentrations causing less than 20% cell death. Biofilm inhibition by (lin-SB056-1)2-K was reported both for the reference strain PAO1 and cystic fibrosis lung isolates of P. aeruginosa. In addition, using fluorescence microscopy, a significant decrease in biofilm-like structures associated
with 3-D cells was observed after peptide exposure. Interestingly, effectiveness of (lin-SB056-1)2-K was also demonstrated in the wound model with a reduction of up to 1-Log unit in biofilm formation by P. aeruginosa PAO1 and wound isolates. Overall, combination treatment and peptide dendrimerization emerged as promising strategies to improve the efficacy of AMPs, especially under challenging host-mimicking conditions. Furthermore, the results of the present study underlined the importance
of evaluating the biological properties of novel AMPs in in vivo-like model systems representative of specific infectious sites in order to make a more realistic prediction of their therapeutic success, and avoid the inclusion of unpromising peptides in animal studies and clinical trials.

Patagonia's biodiversity has been explored from many points of view, however, skin secretions of native amphibians have not been evaluated for antimicrobial peptide research until now. In this sense, Pleurodema thaul is the first amphibian specie to be studied from this large region of South America. Analysis of cDNA-encoding peptide in skin samples allowed identification of four new antimicrobial peptides. The predicted mature peptides were synthesized and all of them showed weak or null antimicrobial activity against Klebsiella pneumoniae, Staphylococcus aureus and Escherichia coli with the exception of thaulin-1, a cationic 26-residue linear, amphipathic, Gly-and Leu-rich peptide with moderate antimicrobial activity against E. coli (MIC of 24.7 μM). AFM and SPR studies suggested a preferential interaction between these peptides and bacterial membranes. Cytotoxicity assays showed that thaulin peptides had minimal effects at MIC concentrations towards human and animal cells. These are the first peptides described for amphibians of the Pleurodema genus. These findings highlight the potential of the Patagonian region's unexplored biodiversity as a source for new molecule discovery.

Plant based antimicrobial compounds have great therapeutic potential as they have lesser side effects as compared with synthetic drugs and also  little  chance  of  development  of  resistance.  Drug  resistance  has been emerging as serious intimidation to human population due to an unsystematic  utilization  of  antibiotics.  Hence,  the  plant,  called  as
“Mother  of  Medicine”,  Terminalia  chebula  has  been  extensively studied  for  its  various  ailments  because  of  its  extraordinary  healing potency  bring  out  by  the  existence  of  numerous  phytoconstitutents. This  present  explorative  study  has  been  projected  to  elicit  an immense aid for the researchers to understand about the pleiotrophic
evaluat ion of Haritaki in a highly structured approach.