Beta adrenergic receptor antagonist can modify Pseudomonas aeruginosa biofilm formation in vitro: Implications for chronic wounds

Abstract

Non-healing wounds are a major medical challenge, affecting over 6.5 million people in the US alone, with associated healthcare costs of about $16 billion annually. They can result in prolonged hospitalizations, work loss, disability, poor quality of life, and in diabetic patients with foot ulcers, amputation of the affected limb in 25% of patients. Though chronic ulcers may arise from different underlying diseases, the unifying feature is chronic infection, driving persistent inflammation that prolongs the healing process. One of the most frequently cultured or genetically identified pathogens in skin wounds is Pseudomonas aeruginosa.This species avidly forms biofilms in the wound that impede bacterial eradication by the host's immune mechanisms and limit efficacy of systemic antibiotics. Thus, non-antibiotic approaches to limit the growth and biofilm formation of this wound pathogen would be an advance in the treatment of chronic wounds.Prior work has demonstrated that the growth of other microbial species can be modulated by catecholamine agonists and antagonists of the adrenergic receptors (ARs). Here, we demonstrate that not only can the growth of this common wound pathogen be modulated by catecholamines, but also that the beta-AR antagonists can significantly decrease their growth, and importantly, limit their ability to form biofilms. These findings suggest that beta adrenergic antagonists may have a therapeutic role in the treatment of chronic skin wounds.

Dronedarone Enhances the Antibacterial Activity of Polymyxin B and Inhibits the Quorum Sensing System by Interacting with LuxS

“…25−30 The ability of β-adrenoreceptor antagonists or blockers to inhibit the QS system has been demonstrated by previous studies. 13,14,31 However, the target of QS suppression was not been identified.…”

“…Dronedarone blocks potassium, sodium, and L-type calcium currents and exerts antiadrenergic effects by noncompetitive binding to β-adrenergic receptors . However, when nonantibiotic drugs are used as antibiotic potentiators, their mechanisms of action are usually different from their original pharmacological effects. − The ability of β-adrenoreceptor antagonists or blockers to inhibit the QS system has been demonstrated by previous studies. ,, However, the target of QS suppression was not been identified.…”

“…coli, Salmonella , Campylobacter , and P. aeruginosa. − Bacterial QS systems and espionage and adrenergic hormone-induced virulence can be inhibited by blockers of β-adrenergic signaling. , Therefore, we speculate that this class of drugs has the potential to be used as antibacterial adjuvants.…”

Mechanism and application of β‐adrenoceptor blockers in soft tissue wound healing

“…Previous studies have shown that catecholamines increase the number of Pseudomonas aeruginosa after antibiotic therapy 85 . P. aeruginosa , the most commonly colonized bacterium in skin wounds, is inhibited by β‐blockers leading to a decrease in biofilm formation 86 . Bacterial AR exposed to stress hormones can also alter their gene expression to adapt to the injury environment for long‐term survival 87 .…”

“…85 P. aeruginosa, the most commonly colonized bacterium in skin wounds, is inhibited by β-blockers leading to a decrease in biofilm formation. 86 Bacterial AR exposed to stress hormones can also alter their gene expression to adapt to the injury environment for long-term survival. 87 Therefore, β-blockers exert an anti-virulence effect, while inhibiting the QS, hence playing a role in preventing infection and promoting wound healing.…”