Abstract
Antibiotic resistance and biofilm-related infections, persistent in conventional antimicrobial treatment, are continuously increasing and represent a major health problem worldwide. Therefore, the development of new effective treatments to prevent and treat biofilm-related infections represents a crucial challenge. Unfortunately, the extensive use of antibiotics has led to an increase of resistant bacteria with the subsequent loss of effectivity of commercial antibiotics, mainly due to antibiotic resistance and the ability of some bacteria to form microbial communities in biotic or abiotic surfaces (biofilms). In some cases, these biofilms are resistant to high concentrations of antibiotics that lead to treatment failure and recurrence of the associated infections. In the fight against microbial resistance, the combination of traditional antibiotics with new compounds (combination therapy) is an alternative that is becoming more extensive in the medical field. In this work, we studied the cooperative effects between levofloxacin, an approved antibiotic, and peptides or cationic dendritic molecules, compounds that are emerging as a feasible solution to overcome the problem of microbial resistance caused by pathogenic biofilms. We studied a new therapeutic approach that involves the use of levofloxacin in combination with a cationic carbosilane dendron, called MalG2(SNHMe2Cl)4, or a synthetic cell-penetrating peptide, called gH625, conjugated to the aforementioned dendron. To carry out the study, we used two combinations (1) levofloxacin/dendron and (2) levofloxacin/dendron-peptide nanoconjugate. The results showed the synergistic effect of the combination therapy to treat Staphylococcus aureus biofilms. In addition, we generated a fluorescein labeled peptide that allowed us to observe the conjugate (dendron-peptide) localization throughout the bacterial biofilm by confocal laser scanning microscopy.
Highlights
IntroductionInfectious diseases have been caused by bacteria with specific pathogenic mechanisms and antibiotic and vaccine developments against pathogenic microorganisms have achieved a remarkable efficiency in their control
Introduction conditions of the Creative CommonsIn the last century, infectious diseases have been caused by bacteria with specific pathogenic mechanisms and antibiotic and vaccine developments against pathogenic microorganisms have achieved a remarkable efficiency in their control
Considering the ability of cationic carbosilane dendritic systems to inhibit the formation of S. aureus biofilms [25], this work aims to analyze the efficiency of the combination therapy of a cationic carbosilane dendron with LEV or a cell-penetrating peptide (CPP) peptide in the prevention and eradication of S. aureus biofilms
Summary
Infectious diseases have been caused by bacteria with specific pathogenic mechanisms and antibiotic and vaccine developments against pathogenic microorganisms have achieved a remarkable efficiency in their control. The remarkable adaptation mechanisms of pathogenic bacteria have generated diverse defense mechanisms against antibiotics, which cause a severe global threat to public health [1,2,3]. Among the bacterial mechanisms of resistance, biofilm formation represents a remarkable implication [4]. These cell structures allow microorganisms to create a multilayer community that makes it easier for them to survive in unfavorable environments [5]. The formation of these structures is a self-defense mechanism that protects them from the innate and adaptive host immune responses and from antimicrobial treatments
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