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TCP-25 Combination Therapy: Boosting the Effects of a Host Defense Peptide

Patil, Manali (2023) MOBN02 20222
Degree Projects in Molecular Biology
Popular Abstract
TCP-25 Combination Therapy: Boosting the Effects of a Host Defense Peptide

Wound infection is defined as the existence of pathogenic bacteria that multiply inside the wound and cause tissue or host damage. The process of wound repair is carried out in multiple steps. These steps restore tissue integrity and function in the majority of cases. Toll-like receptors (TLRs), which are essential for normal wound healing, could become hyperactive in wounds and cause localized dysfunctional inflammation that slows down the healing process. This might impede healing, increase vulnerability to infections and trigger a systemic acute reaction. Conventional anti-infective therapies largely target microorganisms and do not tackle the other specific... (More)
TCP-25 Combination Therapy: Boosting the Effects of a Host Defense Peptide

Wound infection is defined as the existence of pathogenic bacteria that multiply inside the wound and cause tissue or host damage. The process of wound repair is carried out in multiple steps. These steps restore tissue integrity and function in the majority of cases. Toll-like receptors (TLRs), which are essential for normal wound healing, could become hyperactive in wounds and cause localized dysfunctional inflammation that slows down the healing process. This might impede healing, increase vulnerability to infections and trigger a systemic acute reaction. Conventional anti-infective therapies largely target microorganisms and do not tackle the other specific challenges that remain unsolved and have the potential to cause various adverse effects on patients.

Antimicrobial peptides (AMPs) are cutting-edge alternatives for conventional antibiotics that have recently attracted a lot of attention. AMPs, which originate in the host defense system, are part of the innate immune system. AMPs have anti-inflammatory and antibacterial effects. Thrombin-derived C-terminal peptides (TCPs) are part of AMPs. TCP is produced in the body in response to wounding and it is crucial to the coagulation cascade that is required for wound healing. Multiple TCPs exist in wounds, and they can aggregate bacteria and endotoxins and show dual anti-infective and anti-endotoxic effects. It showed therapeutic potential in experimental models of infection and endotoxic shock.

Although TCP-25 has broad-spectrum activity against numerous pathogens, there is a need to boost its effects in the body against P. aeruginosa bacterial strains and biofilms. This project aims to use TCP-25 hydrogel with ethylenediaminetetraacetic acid (EDTA) as a new formulation of TCP-25 gel to investigate the effect of adding EDTA to TCP-25 hydrogel on antibacterial and antibiofilm activity through the use of both in vitro and in vivo methods.

TCP-25-EDTA hydrogel enhanced the effects of the peptide against clinically important bacterial strains: P. aeruginosa and S. aureus. The hydrogel has a substantial effect in vitro against multiple gram-positive and gram-negative pathogens. TCP-25 alone showed a bacteriostatic effect, but when combined with EDTA, particularly at pH 5, TCP-25's effects on planktonic and biofilm-associated bacteria are massively increased in vitro. Compared to the original TCP-25 hydrogel, a TCP-25-EDTA hydrogel showed improved efficacy against P. aeruginosa bacterial strains and biofilms relevant to in vitro and in vivo work.

Master’s Degree Project in Molecular Biology, Genetics and Biotechnology
45 credits 2022-2023
Department of Biology, Lund University
Advisor: Manoj Puthia
Advisors Unit/Department: Division of Dermatology and Venereology, Department of Clinical Sciences (Less)
Please use this url to cite or link to this publication:
author
Patil, Manali
supervisor
organization
course
MOBN02 20222
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9114069
date added to LUP
2023-05-05 15:48:25
date last changed
2023-05-05 15:48:25
@misc{9114069,
  author       = {{Patil, Manali}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{TCP-25 Combination Therapy: Boosting the Effects of a Host Defense Peptide}},
  year         = {{2023}},
}