Models of In-Vivo Bacterial Infections for the Development of Antimicrobial Peptide-based Drugs

The emergence of drug-resistant bacteria emphasizes the urgent need for novel antibiotics. The antimicrobial peptide TS shows extensive antibacterial activity in vitro and in vivo, especially in gram-negative bacteria; however, its antibacterial mechanism is unclear. Here, we find that TS without hemolytic activity disrupts the integrity of the outer bacterial cell membrane by displacing divalent cations and competitively binding lipopolysaccharides. In addition, the antimicrobial peptide TS can inhibit and kill E. coli by disintegrating the bacteria from within by interacting with bacterial DNA. Thus, antimicrobial peptide TS’s multiple antibacterial mechanisms may not easily induce bacterial resistance, suggesting use as an antibacterial drug to be for combating bacterial infections in the future.

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NONINVASIVE OPTICAL IMAGING OF STAPHYLOCOCCUS AUREUS INFECTION IN VIVO USING AN ANTIMICROBIAL PEPTIDE FRAGMENT BASED NEAR-INFRARED FLUORESCENT PROBES

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545813500260 ◽

2013 ◽

Vol 06 (03) ◽

pp. 1350026 ◽

Cited By ~ 9

Author(s):

CUICUI LIU ◽

YUEQING GU

Keyword(s):

Staphylococcus Aureus ◽

Bacterial Infection ◽

Antimicrobial Peptide ◽

Optical Imaging ◽

Bacterial Infections ◽

Near Infrared ◽

Peptide Fragment ◽

Imaging Probe ◽

Aureus Infection

The diagnosis of bacterial infections remains a major challenge in medicine. Optical imaging of bacterial infection in living animals is usually conducted with genetic reporters such as light-emitting enzymes or fluorescent proteins. However, there are many circumstances where genetic reporters are not applicable, and there is an urgent need for exogenous synthetic probes that can selectively target bacteria. Optical imaging of bacteria in vivo is much less developed than methods such as radioimaging and MRI. Furthermore near-infrared (NIR) dyes with emission wavelengths in the region of 650–900 nm can propagate through two or more centimeters of tissue and may enable deeper tissue imaging if sensitive detection techniques are employed. Here we constructed an antimicrobial peptide fragment UBI29-41-based near-infrared fluorescent imaging probe. The probe is composed of UBI29-41 conjugated to a near infrared dye ICG-Der-02. UBI29-41 is a cationic antimicrobial peptide that targets the anionic surfaces of bacterial cells. The probe allows detection of Staphylococcus aureus infection (5 × 107 cells) in a mouse local infection model using whole animal near-infrared fluorescence imaging. Furthermore, we demonstrate that the UBI29-41-based imaging probe can selectively accumulate within bacteria. The significantly higher accumulation in bacterial infection suggests that UBI29-41-based imaging probe may be a promising imaging agent to detect bacterial infections.

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Ethanol Extract Of Centella Asiatica (L.) Urban Leaves Effectively Inhibit Streptococcus pyogenes and Pseudomonas aeruginosa by Invitro Test

Tropical Health and Medical Research ◽

10.35916/thmr.v0i0.23 ◽

2020 ◽

Vol 2 (2) ◽

pp. 69-76

Author(s):

Dini Aulia Azmi ◽

Nurlailah Nurlailah ◽

Ratih Dewi Dwiyanti

Keyword(s):

Pseudomonas Aeruginosa ◽

Streptococcus Pyogenes ◽

Bacterial Infections ◽

Herbal Medicines ◽

Centella Asiatica ◽

Ethanol Extract ◽

Dilution Method ◽

Initial Stage ◽

Independent Variable

Streptococcus pyogenes and Pseudomonas aeruginosa are some of the causes of infectious diseases. Centella asiatica (L.) Urban has many benefits for humans, including overcoming fever, anti-bacterial, and anti-inflammatory. This study aims to determine the inhibition of Centella asiatica (L.) Urban leaves ethanol extract on the growth of Streptococcus pyogenes and Pseudomonas aeruginosa. This research is the initial stage of the development of herbal medicines to treat Streptococcus pyogenes and Pseudomonas aeruginosa infections. The independent variable was the concentration of ethanol extract of Centella asiatica (L.) Urban leaves and the dependent variable was the growth of Streptococcus pyogenes and Pseudomonas aeruginosa. The anti-bacterial activity test was carried out by the liquid dilution method. The concentrations used are 20%, 40%, 60%, 80%. 100% The results showed that the minimum inhibitory concentration (MIC) against Streptococcus pyogenes: 40% and Pseudomonas aeruginosa: 40%. Minimum bactericidal concentration (MBC) results for Streptococcus pyogenes: 60% and Pseudomonas aeruginosa: 60%. So it can be concluded that there is inhibition of the ethanol extract of Centella asiatica (L.) Urban leaves on the growth of Streptococcus pyogenes and Pseudomonas aeruginosa. Centella Asiatica (L.) Urban extract has potential as herbal medicine against bacterial infections but requires further research to determine its effect in vivo.

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Garlic Extract (Allium sativum L.) Effectively Inhibits Staphylococcus aureus and Escherichia coli by Invitro Test

Tropical Health and Medical Research ◽

10.35916/thmr.v0i0.22 ◽

2020 ◽

Vol 2 (2) ◽

pp. 61-68

Author(s):

Agnina Listya Anggraini ◽

Ratih Dewi Dwiyanti ◽

Anny Thuraidah

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Bacterial Infections ◽

Allium Sativum ◽

Antibacterial Properties ◽

Herbal Medicines ◽

Garlic Extract ◽

Dilution Method ◽

Initial Stage

Infection is a disease caused by the presence of pathogenic microbes, including Staphylococcus aureus and Escherichia coli. Garlic (Allium sativum L.) has chemical contents such as allicin, alkaloids, flavonoids, saponins, tannins, and steroids, which can function as an antibacterial against Staphylococcus aureus and Escherichia coli. This study aims to determine the antibacterial properties of garlic extract powder against Staphylococcus aureus and Escherichia coli. This research is the initial stage of the development of herbal medicines to treat Staphylococcus aureus and Escherichia coli infections. The antibacterial activity test was carried out by the liquid dilution method. The concentrations used were 30 mg/mL, 40 mg/mL, 50 mg/mL, 60 mg/mL and 70 mg/mL. The results showed that the Minimum Inhibitory Concentration (MIC) against Staphylococcus aureus and Escherichia coli was 40 mg/mL and 50 mg / mL. Minimum Bactericidal Concentration (MBC) results for Staphylococcus aureus and Escherichia coli are 50 mg/mL and 70 mg/mL. Based on the Simple Linear Regression test, the R2 value of Staphylococcus aureus and Escherichia coli is 0.545 and 0.785, so it can be concluded that there is an effect of garlic extract powder on the growth of Staphylococcus aureus and Escherichia coli by 54.5% and 78.5%. Garlic (Allium sativum L.) extract powder has potential as herbal medicine against bacterial infections but requires further research to determine its effect in vivo.

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In vivo activity and low toxicity of the second-generation antimicrobial peptide DGL13K

PLoS ONE ◽

10.1371/journal.pone.0216669 ◽

2019 ◽

Vol 14 (5) ◽

pp. e0216669 ◽

Cited By ~ 11

Author(s):

Sven-Ulrik Gorr ◽

Craig M. Flory ◽

Robert J. Schumacher

Keyword(s):

Antimicrobial Peptide ◽

Second Generation ◽

Low Toxicity

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AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections

Scientific Reports ◽

10.1038/s41598-021-90573-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nathaniel B. Bone ◽

Eugene J. Becker ◽

Maroof Husain ◽

Shaoning Jiang ◽

Anna A. Zmijewska ◽

...

Keyword(s):

Bacterial Infections ◽

Pathogenic Bacteria ◽

Inflammatory Responses ◽

Abdominal Sepsis ◽

Immune Defense ◽

Bacterial Killing ◽

Lung Infections ◽

Sepsis Survivors ◽

The Impact

AbstractMetabolic and bioenergetic plasticity of immune cells is essential for optimal responses to bacterial infections. AMPK and Parkin ubiquitin ligase are known to regulate mitochondrial quality control mitophagy that prevents unwanted inflammatory responses. However, it is not known if this evolutionarily conserved mechanism has been coopted by the host immune defense to eradicate bacterial pathogens and influence post-sepsis immunosuppression. Parkin, AMPK levels, and the effects of AMPK activators were investigated in human leukocytes from sepsis survivors as well as wild type and Park2−/− murine macrophages. In vivo, the impact of AMPK and Parkin was determined in mice subjected to polymicrobial intra-abdominal sepsis and secondary lung bacterial infections. Mice were treated with metformin during established immunosuppression. We showed that bacteria and mitochondria share mechanisms of autophagic killing/clearance triggered by sentinel events that involve depolarization of mitochondria and recruitment of Parkin in macrophages. Parkin-deficient mice/macrophages fail to form phagolysosomes and kill bacteria. This impairment of host defense is seen in the context of sepsis-induced immunosuppression with decreased levels of Parkin. AMPK activators, including metformin, stimulate Parkin-independent autophagy and bacterial killing in leukocytes from post-shock patients and in lungs of sepsis-immunosuppressed mice. Our results support a dual role of Parkin and AMPK in the clearance of dysfunctional mitochondria and killing of pathogenic bacteria, and explain the immunosuppressive phenotype associated Parkin and AMPK deficiency. AMPK activation appeared to be a crucial therapeutic target for the macrophage immunosuppressive phenotype and to reduce severity of secondary bacterial lung infections and respiratory failure.

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The antimicrobial potential of cannabidiol

Communications Biology ◽

10.1038/s42003-020-01530-y ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Mark A. T. Blaskovich ◽

Angela M. Kavanagh ◽

Alysha G. Elliott ◽

Bing Zhang ◽

Soumya Ramu ◽

...

Keyword(s):

Bacterial Infections ◽

Modern Medicine ◽

Gram Negative Bacteria ◽

Gram Negative ◽

New Class ◽

Clostridioides Difficile ◽

Excellent Activity ◽

Induce Resistance ◽

First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

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Developing Fluoromodule-based Probes for in vivo Monitoring the Bacterial Infections and Antibiotic Responses

Talanta ◽

10.1016/j.talanta.2021.122610 ◽

2021 ◽

pp. 122610

Author(s):

Xiang Wang ◽

Qinghua Wang ◽

Qingyang Zhang ◽

Xiaowan Han ◽

Shengnan Xu ◽

...

Keyword(s):

Bacterial Infections ◽

In Vivo Monitoring

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Mammary gland 3D cell culture systems in farm animals

Veterinary Research ◽

10.1186/s13567-021-00947-5 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Laurence Finot ◽

Eric Chanat ◽

Frederic Dessauge

Keyword(s):

Cell Culture ◽

Mammary Gland ◽

Bacterial Infections ◽

Three Dimensional ◽

3D Cell Culture ◽

Farm Animals ◽

Culture Systems ◽

Cell Culture Systems

AbstractIn vivo study of tissue or organ biology in mammals is very complex and progress is slowed by poor accessibility of samples and ethical concerns. Fortunately, however, advances in stem cell identification and culture have made it possible to derive in vitro 3D “tissues” called organoids, these three-dimensional structures partly or fully mimicking the in vivo functioning of organs. The mammary gland produces milk, the source of nutrition for newborn mammals. Milk is synthesized and secreted by the differentiated polarized mammary epithelial cells of the gland. Reconstructing in vitro a mammary-like structure mimicking the functional tissue represents a major challenge in mammary gland biology, especially for farm animals for which specific agronomic questions arise. This would greatly facilitate the study of mammary gland development, milk secretion processes and pathological effects of viral or bacterial infections at the cellular level, all with the objective of improving milk production at the animal level. With this aim, various 3D cell culture models have been developed such as mammospheres and, more recently, efforts to develop organoids in vitro have been considerable. Researchers are now starting to draw inspiration from other fields, such as bioengineering, to generate organoids that would be more physiologically relevant. In this chapter, we will discuss 3D cell culture systems as organoids and their relevance for agronomic research.

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Phage-Encoded Endolysins

Antibiotics ◽

10.3390/antibiotics10020124 ◽

2021 ◽

Vol 10 (2) ◽

pp. 124

Author(s):

Fatma Abdelrahman ◽

Maheswaran Easwaran ◽

Oluwasegun I. Daramola ◽

Samar Ragab ◽

Stephanie Lynch ◽

...

Keyword(s):

Clinical Trials ◽

Cell Wall ◽

Antibiotic Resistance ◽

Bacterial Infections ◽

Therapeutic Strategies ◽

Therapeutic Application ◽

Significant Evidence ◽

Crucial Information

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.

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