Antimicrobial Peptides: A Promising Avenue for Human Healthcare

2020 ◽  
Vol 21 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Girish M. Bhopale
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Current Status ◽  
Antimicrobial Drugs ◽  
Spectrum Activity ◽  
Low Levels ◽  
Human Healthcare ◽  
Broad Spectrum Activity ◽  
Promising Avenue

Antimicrobial drugs resistant microbes have been observed worldwide and therefore alternative development of antimicrobial peptides has gained interest in human healthcare. Enormous progress has been made in the development of antimicrobial peptide during the last decade due to major advantages of AMPs such as broad-spectrum activity and low levels of induced resistance over the current antimicrobial agents. This review briefly provides various categories of AMP, their physicochemical properties and mechanism of action which governs their penetration into microbial cell. Further, the recent information on current status of antimicrobial peptide development, their applications and perspective in human healthcare are also described.

scholarly journals Beneficial Impacts of Incorporating the Non-Natural Amino Acid Azulenyl-Alanine into the Trp-Rich Antimicrobial Peptide buCATHL4B

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 421
Author(s):  
Areetha R. D’Souza ◽  
Matthew R. Necelis ◽  
Alona Kulesha ◽  
Gregory A. Caputo ◽  
Olga V. Makhlynets
Keyword(s):  
Amino Acid ◽  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Mechanism Of Action ◽  
Bactericidal Activity ◽  
Antimicrobial Agents ◽  
Human Cells ◽  
Side Chains ◽  
Natural Amino Acid ◽  
Proteolytic Stability

Antimicrobial peptides (AMPs) present a promising scaffold for the development of potent antimicrobial agents. Substitution of tryptophan by non-natural amino acid Azulenyl-Alanine (AzAla) would allow studying the mechanism of action of AMPs by using unique properties of this amino acid, such as ability to be excited separately from tryptophan in a multi-Trp AMPs and environmental insensitivity. In this work, we investigate the effect of Trp→AzAla substitution in antimicrobial peptide buCATHL4B (contains three Trp side chains). We found that antimicrobial and bactericidal activity of the original peptide was preserved, while cytocompatibility with human cells and proteolytic stability was improved. We envision that AzAla will find applications as a tool for studies of the mechanism of action of AMPs. In addition, incorporation of this non-natural amino acid into AMP sequences could enhance their application properties.

scholarly journals 1588. Delafloxacin Activity Against Staphylococcus aureus with Reduced Susceptibility or Resistance to Methicillin, Vancomycin, Daptomycin, or Linezolid

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S579-S580
Author(s):  
Louis D Saravolatz ◽  
Joan Pawlak
Keyword(s):  
Antimicrobial Agents ◽  
Minimal Bactericidal Concentration ◽  
Limited Data ◽  
Methicillin Resistant ◽  
Mueller Hinton ◽  
Spectrum Activity ◽  
Resistant Strains ◽  
Gram Negative Organisms ◽  
Mueller Hinton Broth ◽  
Broad Spectrum Activity

Abstract Background Delafloxacin is a recently approved anionic fluoroquinolone antibiotic with broad-spectrum activity against Gram-positive and Gram-negative organisms. The drug has been approved for patients with acute bacterial skin and skin structure infections including those caused by methicillin-resistant S. aureus. There is limited data available against methicillin-resistant S. aureus blood isolates (MRSABI), vancomycin intermediate strains (VISA), vancomycin-resistant strains (VRSA), daptomycin non-susceptible strains (DNSSA) and linezolid-resistant S. aureus (LRSA). Methods Antimicrobial activity of delafloxacin, levofloxacin, vancomycin, daptomycin, ceftaroline, and linezolid was determined against recent (2016–2018) MRSABI (110), VRSA (15), VISA (35), DNSSA (40), and LRSA (6). Broth microdilution testing using Mueller–Hinton broth was used to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) according to CLSI guidelines. FDA breakpoints were used to determine delafloxacin susceptibility, and CLSI breakpoints were used for all other antibiotics. Results Antimicrobial MIC90 expressed in mg/L and (% susceptible) None of the LRSA were susceptible to delafloxacin or levofloxacin. All strains that were susceptible to the antimicrobial agents above had an MBC that was the same as the MIC or one dilution greater except for linezolid which demonstrated an MBC that was more than eight-fold greater than the MIC. For MRSABI isolates with a levofloxacin MIC ≥ 8 mg/L (55/110) suggesting multiple mutations in the quinolone-resistant determining region, the delafloxacin MIC90 was 1 mg/L with a 36.4% susceptibility rate. Conclusion Delafloxacin demonstrates superior activity to levofloxacin against recent MRSA blood isolates, VISA, VRSA, and DNSSA. Disclosures All authors: No reported disclosures.

scholarly journals A Uniform In Vitro Efficacy Dataset to Guide Antimicrobial Peptide Design

Data ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 27 ◽  
Author(s):  
Deepesh Nagarajan ◽  
Tushar Nagarajan ◽  
Neha Nanajkar ◽  
Nagasuma Chandra
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Multi Drug Resistance ◽  
Peptide Design ◽  
Drug Candidates ◽  
The Face ◽  
Conventional Antibiotics ◽  
Different Sources

Antimicrobial peptides are ubiquitous molecules that form the innate immune system of organisms across all kingdoms of life. Despite their prevalence and early origins, they continue to remain potent natural antimicrobial agents. Antimicrobial peptides are therefore promising drug candidates in the face of overwhelming multi-drug resistance to conventional antibiotics. Over the past few decades, thousands of antimicrobial peptides have been characterized in vitro, and their efficacy data are now available in a multitude of public databases. Computational antimicrobial peptide design attempts typically use such data. However, utilizing heterogenous data aggregated from different sources presents significant drawbacks. In this report, we present a uniform dataset containing 20 antimicrobial peptides assayed against 30 organisms of Gram-negative, Gram-positive, mycobacterial, and fungal origin. We also present circular dichroism spectra for all antimicrobial peptides. We draw simple inferences from this data, and we discuss what characteristics are essential for antimicrobial peptide efficacy. We expect our uniform dataset to be useful for future projects involving computational antimicrobial peptide design.

scholarly journals Identification of a Genetic Locus Responsible for Antimicrobial Peptide Resistance inClostridium difficile

2010 ◽  
Vol 79 (1) ◽  
pp. 167-176 ◽  
Author(s):  
Shonna M. McBride ◽  
Abraham L. Sonenshein
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Abc Transporter ◽  
Genetic Locus ◽  
Polymyxin B ◽  
Transcriptional Analysis ◽  
Cationic Antimicrobial Peptide ◽  
Low Levels ◽  
Antimicrobial Peptide Resistance ◽  
Abc Transporter Genes

ABSTRACTClostridium difficilecauses chronic intestinal disease, yet little is understood about how the bacterium interacts with and survives in the host. To colonize the intestine and cause persistent disease, the bacterium must circumvent killing by host innate immune factors, such as cationic antimicrobial peptides (CAMPs). In this study, we investigated the effect of model CAMPs on growth and found thatC. difficileis not only sensitive to these compounds but also responds to low levels of CAMPs by expressing genes that lead to CAMP resistance. By plating the bacterium on medium containing the CAMP nisin, we isolated a mutant capable of growing in three times the inhibitory concentration of CAMPs. This mutant also showed increased resistance to the CAMPs gallidermin and polymyxin B, demonstrating tolerance to different types of antimicrobial peptides. We identified the mutated gene responsible for the resistance phenotype as CD1352. This gene encodes a putative orphan histidine kinase that lies adjacent to a predicted ABC transporter operon (CD1349 to CD1351). Transcriptional analysis of the ABC transporter genes revealed that this operon was upregulated in the presence of nisin in wild-type cells and was more highly expressed in the CD1352 mutant. The insertional disruption of the CD1349 gene resulted in significant decreases in resistance to the CAMPs nisin and gallidermin but not polymyxin B. Because of their role in cationic antimicrobial peptide resistance, we propose the designationcprABCfor genes CD1349 to CD1351 andcprKfor the CD1352 gene. These results provide the first evidence of aC. difficilegene associated with antimicrobial peptide resistance.

scholarly journals Destruction of Staphylococcus aureus biofilms by combining an antibiotic with subtilisin A or calcium gluconate

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
JingJing Liu ◽  
Jean-Yves Madec ◽  
Alain Bousquet-Mélou ◽  
Marisa Haenni ◽  
Aude A. Ferran
Keyword(s):  
Calcium Gluconate ◽  
Laser Scanning ◽  
Extracellular Polymeric Substances ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Antimicrobial Drugs ◽  
The Matrix ◽  
Spectrum Activity ◽  
Biofilm Bacteria ◽  
Broad Spectrum Activity

AbstractIn S. aureus biofilms, bacteria are embedded in a matrix of extracellular polymeric substances (EPS) and are highly tolerant to antimicrobial drugs. We thus sought to identify non-antibiotic substances with broad-spectrum activity able to destroy the EPS matrix and enhance the effect of antibiotics on embedded biofilm bacteria. Among eight substances tested, subtilisin A (0.01 U/mL) and calcium gluconate (CaG, Ca2+ 1.25 mmol/L) significantly reduced the biomass of biofilms formed by at least 21/24 S. aureus isolates. Confocal laser scanning microscopy confirmed that they both eliminated nearly all the proteins and PNAG from the matrix. By contrast, antibiotics alone had nearly no effect on biofilm biomass and the selected one (oxytetracycline-OTC) could only slightly reduce biofilm bacteria. The combination of OTC with CaG or subtilisin A led to an additive reduction (average of 2 log10 CFU/mL) of embedded biofilm bacteria on the isolates susceptible to OTC (MBC < 10 μg/mL, 11/24). Moreover, these two combinations led to a reduction of the embedded biofilm bacteria higher than 3 log10 CFU/mL for 20–25% of the isolates. Further studies are now required to better understand the factors that cause the biofilm produced by specific isolates (20–25%) to be susceptible to the combinations.

scholarly journals Efficacy and Safety of Levonadifloxacin in the Management of Community-Acquired Bacterial Pneumonia (CABP): Findings of a Retrospective, Real-World, Multi-centre Study

2021 ◽  
Vol 6 (12) ◽  
pp. 919-925
Author(s):  
Dr. Prahlad Prabhudesai ◽  
Dr. Ashish Jain ◽  
Dr. Prashant Borade ◽  
Dr. Abhijeet Khandelwal ◽  
Kapil Mehta ◽  
...  
Keyword(s):  
Real World ◽  
Bacterial Pneumonia ◽  
Antimicrobial Agents ◽  
Global Public Health ◽  
Efficacy And Safety ◽  
Multi Centre Study ◽  
Healthcare Facilities ◽  
Post Marketing ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

Background: Community-acquired bacterial pneumonia (CABP) remains a global public health threat and is a leading cause of hospitalization and infection-linked mortality. Levonadifloxacin is a novel benzoquinolizine antibiotic with a broad-spectrum activity including methicillin-resistant Staphylococcus aureus (MRSA) and CABP-pathogens. Methods: This multi-centre, retrospective, post-marketing, real-world study assessed the efficacy and safety of levonadifloxacin oral and/or intravenous therapy in the treatment of CABP. Data from 338 patients above 17 years-of-age who received levonadifloxacin (oral or intravenous or both) was collected from 89 healthcare facilities across India. Information on clinical condition, comorbidities, complications, and details of concurrent therapy (including antimicrobial agents) was also collected. Study outcomes were clinical and microbial success at the end of therapy while safety was assessed based on clinical and laboratory adverse events. Results: Of the 338 patients, 244 (72.2%) were male, 93 (27.5%) were female and 1 (0.43%) was a transgender. About 294 (87.0%) patients were hospital-treated and 44 (13%) received outpatient treatment. About 248 (73.4%) patients received intravenous levonadifloxacin treatment, 79 (23.4%) received oral and 11 (3.3%) received intravenous followed by oral levonadifloxacin therapy. The common comorbid conditions were diabetes (14.2%) and hypertension (8.6%). Mean duration of levonadifloxacin therapy was 6.4 days. Clinical and microbial success in levonadifloxacin-treated patients was 95.0% (321/388) and 96.8% (150/155), respectively. Conclusions: Levonadifloxacin showed promising clinical outcomes and safety when used as an intravenous and/or oral for the treatment of CABP, both in outpatients as well as hospitalized patients.

scholarly journals A uniform in vitro efficacy dataset to guide antimicrobial peptide design

2018 ◽  
Author(s):  
Deepesh Nagarajan ◽  
Tushar Nagarajan ◽  
Neha Nanajkar ◽  
Nagasuma Chandra
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Multi Drug Resistance ◽  
Peptide Design ◽  
Drug Candidates ◽  
The Face ◽  
Conventional Antibiotics ◽  
Different Sources

ABSTRACTAntimicrobial peptides are ubiquitous molecules that form the innate immune system of organisms across all kingdoms of life. Despite their prevalence and early origins, they continue to remain potent natural antimicrobial agents. Antimicrobial peptides are therefore promising drug candidates in the face of overwhelming multi-drug resistance to conventional antibiotics. Over the past few decades, thousands of antimicrobial peptides have been characterized in vitro, and their efficacy data is now available in a multitude of public databases. Computational antimicrobial peptide design attempts typically use such data. However, utilizing heterogenous data aggregated from different sources presents significant drawbacks. In this report, we present a uniform dataset containing 20 antimicrobial peptides assayed against 30 organisms spanning gram positive, gram negative, fungal, and mycobacterial origin. We draw inferences from the results of 600 individual MIC assays, and discuss what characteristics are essential for antimicrobial peptide efficacy. We expect our uniform dataset to be useful for future projects involving computational antimicrobial peptide design.

scholarly journals Towards Robust Delivery of Antimicrobial Peptides to Combat Bacterial Resistance

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3048 ◽  
Author(s):  
Matthew Drayton ◽  
Jayachandran N. Kizhakkedathu ◽  
Suzana K. Straus
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Delivery Vehicle ◽  
Peptide Modification ◽  
Number Of Factors ◽  
Microbial Infections ◽  
Spectrum Activity ◽  
Review Current ◽  
Site Release ◽  
Broad Spectrum Activity

Antimicrobial peptides (AMPs), otherwise known as host defence peptides (HDPs), are naturally occurring biomolecules expressed by a large array of species across the phylogenetic kingdoms. They have great potential to combat microbial infections by directly killing or inhibiting bacterial activity and/or by modulating the immune response of the host. Due to their multimodal properties, broad spectrum activity, and minimal resistance generation, these peptides have emerged as a promising response to the rapidly concerning problem of multidrug resistance (MDR). However, their therapeutic efficacy is limited by a number of factors, including rapid degradation, systemic toxicity, and low bioavailability. As such, many strategies have been developed to mitigate these limitations, such as peptide modification and delivery vehicle conjugation/encapsulation. Oftentimes, however, particularly in the case of the latter, this can hinder the activity of the parent AMP. Here, we review current delivery strategies used for AMP formulation, focusing on methodologies utilized for targeted infection site release of AMPs. This specificity unites the improved biocompatibility of the delivery vehicle with the unhindered activity of the free AMP, providing a promising means to effectively translate AMP therapy into clinical practice.

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