Abstract
BackgroundThe global emergence of Acinetobacter baumannii resistance to most conventional antibiotics presents a major therapeutic challenge and necessitates the discovery of new antibacterial agents. The purpose of this study was to investigate in vitro and in vivo anti-biofilm potency of dermcidin-1L (DCD-1L) against extensively drug-resistant (XDR)-, pandrug-resistant (PDR)-, and ATCC19606-A. baumannii.MethodsAfter determination of minimum inhibitory concentration (MIC) of DCD-1L, in vitro anti-adhesive and anti-biofilm activities of DCD-1L were evaluated. Cytotoxicity, hemolytic activity, and the effect of DCD-1L treatment on the expression of various biofilm-associated genes were determined. The inhibitory effect of DCD-1L on biofilm formation in the model of catheter-associated infection, as well as, histopathological examination of the burn wound sites of mice treated with DCD-1L were assessed.ResultsThe bacterial adhesion and biofilm formation in all A. baumannii isolates were inhibited at 2 × , 4 × , and 8 × MIC of DCD-1L, while only 8 × MIC of DCD-1L was able to destroy the pre-formed biofilm in vitro. Also, reduce the expression of genes involved in biofilm formation was observed following DCD-1L treatment. DCD-1L without cytotoxic and hemolytic activities significantly reduced the biofilm formation in the model of catheter-associated infection. In vivo results showed that the count of A. baumannii in infected wounds was significantly decreased and the promotion in wound healing by the acceleration of skin re-epithelialization in mice was observed following treatment with 8 × MIC of DCD-1L.ConclusionsResults of this study demonstrated that DCD-1L can inhibit bacterial attachment and biofilm formation and prevent the onset of infection. Taking these properties together, DCD-1L appears as a promising candidate for antimicrobial and anti-biofilm drug development.
Highlights
Acinetobacter baumannii has become one of the most opportunistic pathogens in clinical settings, especially in patients with infections related to indwelling catheters and burn wound due to the acquisition of resistance genes to most common antibiotics [1].A.Farshadzadeh et al BMC Microbiology (2022) 22:25 baumannii as a drug-resistant strain has acquired antibiotic resistance by obtaining plasmids, transposons, or integrons that carry a set of genes encoding multidrug resistance [2]
A prominent ability to accumulate a variety of resistance mechanisms, from inherent resistance to disinfectants to the ability to survive in stressful environments, making this microorganism multi- or pan- drug-resistant, and the ability to develop biofilm, which greatly increases both persistence and resistance in environments, are considered the main features contributing to the survival of this bacteria [3, 4]
Susceptibility of A. baumannii isolates against DCD‐1L To determine the antimicrobial activity of DCD-1L against A. baumannii isolates the broth microdilution method was used according to the Clinical and Laboratory Standards Institute (CLSI) guideline
Summary
Acinetobacter baumannii has become one of the most opportunistic pathogens in clinical settings, especially in patients with infections related to indwelling catheters and burn wound due to the acquisition of resistance genes to most common antibiotics [1].A.Farshadzadeh et al BMC Microbiology (2022) 22:25 baumannii as a drug-resistant strain has acquired antibiotic resistance by obtaining plasmids, transposons, or integrons that carry a set of genes encoding multidrug resistance [2]. The phenomenon of biofilm formation in A. baumannii strains is not determined by any single genotype or single factor but is a complex biological and multi-factorial process that is regulated by several bacterial genes. It has been revealed that the expression of several genes to be involved in biofilm formation of A. baumannii such as chaperon-usher pilus E (csuE), the outer membrane protein A (OmpA), two-component system (bfmS/bfmR), Acinetobacter baumannii autoinducer synthase (abaI) and poly-β-(1,6)-N-acetyl glucosamine (pnag) [5]. The inactivation of bfmS could reduce biofilm formation in A. baumannii 17,978 type strain [7]. The OmpA (38-kDa) as an outer membrane protein of A. baumannii plays a critical role in bacterial adherence, biofilm formation, and invasion to host cells via interaction with tissue fibronectin. The purpose of this study was to investigate in vitro and in vivo anti-biofilm potency of dermcidin-1L (DCD-1L) against extensively drug-resistant (XDR)-, pandrug-resistant (PDR)-, and ATCC19606-A. baumannii
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