Beyond antibiotics: Emerging antivirulence strategies to combat Pseudomonas aeruginosa in cystic fibrosis.

Pseudomonas aeruginosa is an opportunistic pathogen that poses a significant threat to individuals suffering from cystic fibrosis (CF). The pathogen is highly prevalent in CF individuals and is responsible for chronic infection, resulting in severe tissue damage and poor patient outcome. Prolonged antibiotic administration has led to the emergence of multidrug resistance in P. aeruginosa. In this direction, antivirulence strategies achieving targeted inhibition of bacterial virulence pathways, including quorum sensing, efflux pumps, lectins, and iron chelators, have been explored against CF isolates of P. aeruginosa. Hence, this review article presents a bird's eye view on the pulmonary infections involving P. aeruginosa in CF patients by laying emphasis on factors contributing to bacterial colonization, persistence, and disease progression along with the current line of therapeutics against P. aeruginosa in CF. We further collate scientific literature and discusses various antivirulence strategies that have been tested against P. aeruginosa isolates from CF patients.

Citral and triclosan synergistically silence quorum sensing and potentiate antivirulence response in Pseudomonas aeruginosa.

Among the ESKAPE pathogens, Pseudomonas aeruginosa is an extensively notorious superbug that causes difficult-to-treat infections. Since quorum sensing (QS) directly promotes pseudomonal virulence, targeting QS circuits is a promising approach for disarming phenotypic virulence. Hence, this study scrutinizes the anti-QS, antivirulence, and anti-biofilm potential of citral (CiT; phytochemical) and triclosan (TcN; disinfectant), alone and in combination, against P. aeruginosa PAO1/PA14. The findings confirmed synergism between CiT and TcN and revealed their quorum quenching (QQ) potential. At sub-inhibitory levels, CiT-TcN combination significantly impeded pyocyanin, total bacterial protease, hemolysin, and pyochelin production alongside inhibiting biofilm formation in P. aeruginosa. Moreover, the QQ and antivirulence potential of CiT and TcN was positively correlated by molecular docking studies that predicted strong associations of the drugs with QS receptors of P. aeruginosa. Collectively, the study identifies CiT-TcN as an effective drug combination that harbors QQ, antivirulence, and anti-biofilm prospects against P. aeruginosa.

A comprehensive review on the pharmacological prospects of Terpinen-4-ol: From nature to medicine and beyond.

Owing to their extensive biological potential, essential oils (EOs) and their bioactive phytochemicals have gained attention from the scientific community. Within this domain, Terpinen-4-ol (T-4-ol), a bioactive monoterpene alcohol and the major constituent of tea tree oil (TTO), has made its way into translational research. Recent literature on T-4-ol strongly indicates its diverse pharmacological properties, including but not limited to antimicrobial, antivirulent, anti-oxidant, anti-inflammatory, anti-hypertensive, and anti-cancer effects. Hence, this review is the first to provide a comprehensive overview of the sources, bioavailability, safety, pharmaceutical delivery systems, and multifaceted biological properties of T-4-ol, emphasizing its medicinal potential for widescale application. The antibacterial and antifungal effectiveness of T-4-ol has been discussed, encompassing its role in combating a broad spectrum of bacterial and fungal pathogens. The review delves into the antivirulent prospects of T-4-ol, shedding light on its ability to attenuate virulence and mitigate bacterial pathogenesis. Scientific literature on the anti-oxidant and anti-inflammatory activity of T-4-ol highlighting its role in neutralizing reactive oxygen species and modulating inflammatory pathways has also been collated. Furthermore, the review elaborates on the cardioprotective and anti-hypertensive properties of T-4-ol and augments literature on its anti-cancer mechanism against various cancer cell lines. The review also provides in-depth knowledge of the pharmaceutical formulations of T-4-ol and recent knowledge about its application in clinical/field trials. The exploration of these diverse attributes positions T-4-ol as a promising candidate for further research and therapeutic repurposing in various biomedical applications.

Revitalizing common drugs for antibacterial, quorum quenching, and antivirulence potential against Pseudomonas aeruginosa: in vitro and in silico insights.

In the post-antibiotic era, antivirulence therapies are becoming refractory to the clinical application of existing antimicrobial regimens. Moreover, in an attempt to explore alternate intervention strategies, drug repurposing is gaining attention over development of novel drugs/antimicrobials. With the prevalence of multidrug resistance and high medical burden associated with Pseudomonas aeruginosa, there is an urgent need to devise novel therapeutics to combat this bacterial pathogen. In this context, the present study was undertaken to scrutinize the anti-quorum sensing (QS) and antivirulence potential of commonly consumed drugs such as fexofenadine (FeX), ivermectin (IvM), nitrofurantoin (NiT), levocetrizine (LvC), atorvastatin (AtS), and aceclofenac (AcF), against P. aeruginosa. The methodology involved assessment of antibacterial activity against P. aeruginosa PAO1 and quorum quenching (QQ) potential using Agrobacterium tumefaciens NTL4 biosensor strain. The antivirulence prospects were investigated by estimating the production of hallmark virulence factors in P. aeruginosa accompanied by molecular docking to predict drug associations with the QS receptors. Interestingly, all the drugs harbored antibacterial, anti-QS, and antivirulence potential in vitro, which consequently disrupted QS circuits and attenuated pseudomonal virulence phenotypically by significantly lowering the production of pyocyanin, hemolysin, pyochelin, and total bacterial protease in vitro. Moreover, the findings were validated by computational studies that predicted strong molecular interactions between the test drugs and QS receptors of P. aeruginosa. Hence, this study is the first to suggest the prospect of repurposing FeX, IvM, NiT, LvC, AtS, and AcF against P. aeruginosa.