Infections with Pseudomonas aeruginosa have been marked with the highest priority for surveillance and epidemiological research on the basis of parameters such as incidence, case fatality rates, chronicity of illness, available options for prevention and treatment, health-care utilization, and societal impact. P. aeruginosa is one of the six ESKAPE pathogens that are the major cause of nosocomial infections and are a global threat because of their capacity to become increasingly resistant to all available antibiotics. This review reports on current pre-clinical and clinical advances of anti-pseudomonal therapies in the fields of drug development, antimicrobial chemotherapy, vaccines, phage therapy, non-bactericidal pathoblockers, outer membrane sensitizers, and host defense reinforcement.

Emerging therapies against infections with Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a Gram-negative bacterium causing diseases in plants, animals, and humans, and its drug resistance is a major concern in medical care. Biofilms play an important role in P. aeruginosa drug resistance. Three factors are most important to induce biofilm: quorum sensing (QS), bis-(3'-5')-cyclic diguanosine monophosphate (c-di-GMP), and small RNAs (sRNAs). P. aeruginosa has its own specific QS system (PQS) besides two common QS systems, LasI-LasR and RhlI-RhlR, in bacteria. PQS is interesting not only because there is a negative regulation from RhlR to pqsR but also because the null mutation in PQS leads to a reduced biofilm formation. Furthermore, P. aeruginosa dispersed cells have physiological features that are distinct between the planktonic cells and biofilm cells. In response to a low concentration of c-di-GMP, P. aeruginosa cells can disperse from the biofilms to become planktonic cells. These raise an interesting hypothesis of whether biofilm can be reversed through the QS mechanism in P. aeruginosa. Although a single factor is certainly not sufficient to prevent the biofilm formation, it necessarily explores such possibility. In this hypothesis, the literature is analyzed to determine the negative regulation pathways, and then the transcriptomic data are analyzed to determine whether this hypothesis is workable or not. Unexpectedly, the transcriptomic data reveal a negative regulation between lasI and psqR. Also, the individual cases from transcriptomic data demonstrate the negative regulations of PQS with laslI, laslR, rhlI, and rhlR under different experiments. Based on our analyses, possible strategies to reverse biofilm formation are proposed and their clinic implications are addressed.

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Can Biofilm Be Reversed Through Quorum Sensing in Pseudomonas aeruginosa

The development of drug-resistant microorganisms has become a critical issue for modern medicine and drug discovery and development with severe socio-economic and ecological implications. Since standard and conventional treatment options are generally inefficient, leading to infection persistence and spreading, novel strategies are fundamentally necessary in order to avoid serious global health problems. In this regard, both metal and metal oxide nanoparticles (NPs) demonstrated increased effectiveness as nanobiocides due to intrinsic antimicrobial properties and as nanocarriers for antimicrobial drugs. Among them, gold, silver, copper, zinc oxide, titanium oxide, magnesium oxide, and iron oxide NPs are the most preferred, owing to their proven antimicrobial mechanisms and bio/cytocompatibility. Furthermore, inorganic NPs can be incorporated or attached to organic/inorganic films, thus broadening their application within implant or catheter coatings and wound dressings. In this context, this paper aims to provide an up-to-date overview of the most recent studies investigating inorganic NPs and their integration into composite films designed for antimicrobial therapies.

https://www.mdpi.com/1422-0067/22/9/4595/pdf

Inorganic Nanoparticles and Composite Films for Antimicrobial Therapies.

The role of nanotechnology in combating biofilm-based antibiotic resistance

Staphylococci, like Staphylococcus aureus and S epidermidis, are common colonizers of the human microbiota While being harmless in many cases, many virulence factors result in them being opportunistic pathogens and one of the major causes of hospital-acquired infections worldwide One of these virulence factors is the ability to form biofilms-three-dimensional communities of microorganisms embedded in an extracellular polymeric matrix (EPS) The EPS is composed of polysaccharides, proteins and extracellular DNA, and is finely regulated in response to environmental conditions This structured environment protects the embedded bacteria from the human immune system and decreases their susceptibility to antimicrobials, making infections caused by staphylococci particularly difficult to treat With the rise of antibiotic-resistant staphylococci, together with difficulty in removing biofilms, there is a great need for new treatment strategies The purpose of this review is to provide an overview of our current knowledge of the stages of biofilm development and what difficulties may arise when trying to eradicate staphylococcal biofilms Furthermore, we look into promising targets and therapeutic methods, including bacteriocins and phage-derived antibiofilm approaches

Staphylococcal Biofilms: Challenges and Novel Therapeutic Perspectives.

Anti-PqsR compounds as next-generation antibacterial agents against Pseudomonas aeruginosa: A review

Introduction: Sleeplessness is the most common sleep disorder. In this study, the hypnotic effect of macerated (HAME) and soxhlet (HASE) extract of Lagenaria vulgaris (fruit and seed) and Cucurbita pepo (fruit) were studied in mice. Methods: Extracts and fractions were administered intra-peritoneally (i.p.) in mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Moreover, the influence of flumazenil or naloxone on the hypnotic effects of the extract and its toxic effects were evaluated. Results: The HAME and HASE of C. pepo prolonged the pentobarbital-induced sleep duration at dose of 200 mg/kg. The HAME of L. vulgaris (fruit) at dose of 200 mg/kg increased the sleeping time. The HAME and HASE of L. vulgaris (seed) increased sleep duration at doses of 50 and 100 mg/kg. Besides, flumazenil (2 mg/kg) reversed the effects of both diazepam (P < 0.001 vs. diazepam group), 200 mg/kg of HAME of C. pepo and 50 mg/kg of HAME and HASE of L. vulgaris (seed). All fractions especially ethyl-acetate fraction (EAF) of L. vulgaris (seed) increased the sleep duration. Naloxone reversed the hypnotic effect of HAME and HASE of L. vulgaris (seed). The extracts showed no neurotoxic effects on PC12 and L929 cell lines. Conclusion: The results showed that L. vulgaris (seed and fruit) and C. pepo potentiated pentobarbital hypnosis without toxic influence. The hypnotic effects of L. vulgaris seed was greater than its fruit and C. pepo. The GABA and opioid receptors may play role in the sleep-induction of L. vulgaris seed.

Evaluation of the Sleep-Prolonging Effect of Lagenaria vulgaris and Cucurbita pepo Extracts on Pentobarbital-Induced Sleep and Possible Mechanisms of Action

Ultra selective and high-capacity dummy template molecular imprinted polymer to control quorum sensing and biofilm formation of Pseudomonas aeruginosa.

Amineh Sadat Tajani

Papers

The role of nanotechnology in combating biofilm-based antibiotic resistance

Anti-PqsR compounds as next-generation antibacterial agents against Pseudomonas aeruginosa: A review

Evaluation of the Sleep-Prolonging Effect of Lagenaria vulgaris and Cucurbita pepo Extracts on Pentobarbital-Induced Sleep and Possible Mechanisms of Action

Ultra selective and high-capacity dummy template molecular imprinted polymer to control quorum sensing and biofilm formation of Pseudomonas aeruginosa.

Bacterial biofilms and their resistance mechanisms: a brief look at treatment with natural agents