-
Molecules (Basel, Switzerland) Oct 2022Multi-drug resistance is increasing in the pathogenic bacterium , which is mainly responsible for meningitis and community-acquired pneumonia (CAP), highlighting the...
Multi-drug resistance is increasing in the pathogenic bacterium , which is mainly responsible for meningitis and community-acquired pneumonia (CAP), highlighting the need for new anti-pneumococcal agents. We have identified a potential anti-pneumococcal agent, enol , which acts by hindering the cell division process by perturbing Z-ring dynamics inside the cell. Enol was also shown to inhibit FtsZ polymerization and induce its aggregation in vitro but does not affect the activity of tubulin and alkaline phosphatase. Docking studies show that binds near the T7 loop, which is the catalytic site of FtsZ. Similar effects on Z-ring and FtsZ assembly were observed in , indicating that could be a broad-spectrum anti-bacterial agent useful in targeting Gram-positive bacteria. In conclusion, compound shows strong anti-pneumococcal activity, prompting further pre-clinical studies to explore its potential.
Topics: Cytoskeletal Proteins; Bacterial Proteins; Tubulin; Alkaline Phosphatase; Anti-Bacterial Agents; Bacillus subtilis
PubMed: 36296585
DOI: 10.3390/molecules27206993 -
International Journal of Nanomedicine 2024Nanoparticle systems integrating alginate and chitosan emerge as a promising avenue to tackle challenges in leveraging the potency of pharmacological active agents.... (Review)
Review
Nanoparticle systems integrating alginate and chitosan emerge as a promising avenue to tackle challenges in leveraging the potency of pharmacological active agents. Owing to their intrinsic properties as polysaccharides, alginate and chitosan, exhibit remarkable biocompatibility, rendering them conducive to bodily integration. By downsizing drug particles to the nano-scale, the system enhances drug solubility in aqueous environments by augmenting surface area. Additionally, the system orchestrates extended drug release kinetics, aligning well with the exigencies of chronic drug release requisite for antibacterial therapeutics. A thorough scrutiny of existing literature underscores a wealth of evidence supporting the utilization of the alginate-chitosan nanoparticle system for antibacterial agent delivery. Literature reviews present abundant evidence of the utilization of nanoparticle systems based on a combination of alginate and chitosan for antibacterial agent delivery. Various experiments demonstrate enhanced antibacterial efficacy, including an increase in the inhibitory zone diameter, improvement in the minimum inhibitory concentration, and an enhancement in the bacterial reduction rate. This enhancement in efficacy occurs due to mechanisms involving increased solubility resulting from particle size reduction, prolonged release effects, and enhanced selectivity towards bacterial cell walls, stemming from ionic interactions between positively charged particles and teichoic acid on bacterial cell walls. However, clinical studies remain limited, and there are currently no marketed antibacterial drugs utilizing this system. Hence, expediting clinical efficacy validation is crucial to maximize its benefits promptly.
Topics: Chitosan; Alginates; Anti-Bacterial Agents; Humans; Nanoparticles; Particle Size; Drug Liberation; Drug Carriers; Microbial Sensitivity Tests; Animals; Drug Delivery Systems; Solubility; Bacteria
PubMed: 38832335
DOI: 10.2147/IJN.S469572 -
Polish Journal of Microbiology 2013Bacteriocines are small peptides with anti-bacterial properties. They are produced both by Gram-positive and Gram-negative bacteria. Until now, a few hundred... (Review)
Review
Bacteriocines are small peptides with anti-bacterial properties. They are produced both by Gram-positive and Gram-negative bacteria. Until now, a few hundred bacteriocines were described. Classification of bacteriocines undergoes continuous alterations, as new developments regarding their structure, amino acid sequence and recognised mechanism of their action are available. Some of bacteriocins (lantibiotics) contain atypical amino acids, such as lantionine (Lan), methyllantionine (MeLan), dehydroalanine (Dha), dehydrobutyrine (Dhb), or D-alanine (D-Ala). The best recognized bacteriocines are produced by lactic acid bacteria, including nisine produced by strains of Lactococcus lactis. These bacteriocines have been recognized to be fully safe for humans. At present, nisine is used in food industry, as a preserving agent. Other lactic acid bacteria bacteriocines and probiotic preparations provide an alternative for antibiotics, and are used in food and in animal feed.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacteriocins; Humans; Protein Structure, Secondary
PubMed: 24459827
DOI: No ID Found -
Molecules (Basel, Switzerland) Feb 2011Cationic lipids have long been known to serve as antibacterial and antifungal agents. Prior efforts with attachment of cationic lipids to carbohydrate-based surfaces...
Cationic lipids have long been known to serve as antibacterial and antifungal agents. Prior efforts with attachment of cationic lipids to carbohydrate-based surfaces have suggested the possibility that carbohydrate-attached cationic lipids might serve as antibacterial and antifungal pharmaceutical agents. Toward the understanding of this possibility, we have synthesized several series of cationic lipids attached to a variety of glycosides with the intent of generating antimicrobial agents that would meet the requirement for serving as a pharmaceutical agent, specifically that the agent be effective at a very low concentration as well as being biodegradable within the organism being treated. The initial results of our approach to this goal are presented.
Topics: Anti-Bacterial Agents; Antifungal Agents; Carbohydrate Conformation; Glycosides; Humans; Lipids; Microbial Sensitivity Tests; Molecular Structure; Polyamines; Polyelectrolytes; Salts
PubMed: 21317841
DOI: 10.3390/molecules16021508 -
International Journal of Oral Science Oct 2019Effective control of oral biofilm infectious diseases represents a major global challenge. Microorganisms in biofilms exhibit increased drug tolerance compared with... (Review)
Review
Effective control of oral biofilm infectious diseases represents a major global challenge. Microorganisms in biofilms exhibit increased drug tolerance compared with planktonic cells. The present review covers innovative antimicrobial strategies for controlling oral biofilm-related infections published predominantly over the past 5 years. Antimicrobial dental materials based on antimicrobial agent release, contact-killing and multi-functional strategies have been designed and synthesized for the prevention of initial bacterial attachment and subsequent biofilm formation on the tooth and material surface. Among the therapeutic approaches for managing biofilms in clinical practice, antimicrobial photodynamic therapy has emerged as an alternative to antimicrobial regimes and mechanical removal of biofilms, and cold atmospheric plasma shows significant advantages over conventional antimicrobial approaches. Nevertheless, more preclinical studies and appropriately designed and well-structured multi-center clinical trials are critically needed to obtain reliable comparative data. The acquired information will be helpful in identifying the most effective antibacterial solutions and the most optimal circumstances to utilize these strategies.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Biofilms; Humans; Mouth; Plankton
PubMed: 31570700
DOI: 10.1038/s41368-019-0062-1 -
Bioorganic & Medicinal Chemistry Dec 2016The tetrodecamycins are a group of secondary metabolites that are characterized by the presence of a tetronate ring in their structure. Originally discovered for their... (Review)
Review
The tetrodecamycins are a group of secondary metabolites that are characterized by the presence of a tetronate ring in their structure. Originally discovered for their antibiotic activity against Photobacterium damselae ssp. piscicida, the causative agent of pseudotuberculosis in fish, this family of molecules has also been shown to have potent antibiotic activity against methicillin-resistant Staphylococcus aureus. Due to their small size and highly cyclized nature, they represent an unusual member of the much larger group of bioactive molecules called the tetronates. Herein, we review what is known about the mechanism of action of these molecules and also present a hypothesis for their biosynthesis. A deeper understanding of the tetrodecamycins will provide a more holistic view of the tetronate-family, provide new chemical probes of bacterial biology, and may provide therapeutic lead molecules.
Topics: Anti-Bacterial Agents; Furans; Molecular Structure; Photobacterium; Structure-Activity Relationship
PubMed: 27246856
DOI: 10.1016/j.bmc.2016.05.028 -
Molecules (Basel, Switzerland) Oct 2023Phytochemicals are plant secondary metabolites that show health benefits for humans due to their bioactivity. There is a huge variety of phytochemicals that have already... (Review)
Review
Phytochemicals are plant secondary metabolites that show health benefits for humans due to their bioactivity. There is a huge variety of phytochemicals that have already been identified, and these compounds can act as antimicrobial and neuroprotection agents. Due to their anti-microbial activity and neuroprotection, several phytochemicals might have the potency to be used as natural therapeutic agents, especially for infection and neurodegenerative disease, which have become a global health concern nowadays. According to previous research, there are some connections between infection and neurodegenerative diseases, especially Alzheimer's disease. Hence, this comprehensive review examines different kinds of phytochemicals from natural sources as potential therapeutic agents to reduce infection and improve neurodegenerative disease. An additional large-scale study is needed to establish the connection between infection and neurodegenerative disease and how phytochemicals could improve this condition.
Topics: Humans; Helicobacter pylori; Helicobacter Infections; Neuroprotective Agents; Neurodegenerative Diseases; Anti-Bacterial Agents; Phytochemicals
PubMed: 37894629
DOI: 10.3390/molecules28207150 -
Journal of Applied Microbiology May 2018With the emergence of antibiotic resistance, the interest for antimicrobial agents has recently increased again in public health. Copper was recognized in 2008 by the... (Review)
Review
With the emergence of antibiotic resistance, the interest for antimicrobial agents has recently increased again in public health. Copper was recognized in 2008 by the United States Environmental Protection Agency (EPA) as the first metallic antimicrobial agent. This led to many investigations of the various properties of copper as an antibacterial, antifungal and antiviral agent. This review summarizes the latest findings about 'contact killing', the mechanism of action of copper nanoparticles and the different ways micro-organisms develop resistance to copper.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antiviral Agents; Copper; Drug Resistance, Microbial
PubMed: 29280540
DOI: 10.1111/jam.13681 -
International Journal of Molecular... Aug 2022Biofilms are complex structures formed by bacteria, fungi, or even viruses on biotic and abiotic surfaces, and they can be found in almost any part of the human body.... (Review)
Review
Biofilms are complex structures formed by bacteria, fungi, or even viruses on biotic and abiotic surfaces, and they can be found in almost any part of the human body. The prevalence of biofilm-associated diseases has increased in recent years, mainly because of the frequent use of indwelling medical devices that create opportunities for clinically important bacteria and fungi to form biofilms either on the device or on the neighboring tissues. As a result of their resistance to antibiotics and host immunity factors, biofilms have been associated with the development or persistence of several clinically important diseases. The inability to completely eradicate biofilms drastically increases the burden of disease on both the patient and the healthcare system. Therefore, it is crucial to develop innovative ways to tackle the growth and development of biofilms. This review focuses on dental- and implant-associated biofilm infections, their prevalence in humans, and potential therapeutic intervention strategies, including the recent advances in pharmacology and biomedical engineering. It lists current strategies used to control the formation of clinically important biofilms, including novel antibiotics and their carriers, antiseptics and disinfectants, small molecule anti-biofilm agents, surface treatment strategies, and nanostructure functionalization, as well as multifunctional coatings particularly suitable for providing antibacterial effects to the surface of implants, to treat either dental- or implant-related bacterial infections.
Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Bacteria; Bacterial Infections; Biofilms; Fungi; Humans
PubMed: 36076921
DOI: 10.3390/ijms23179526 -
PLoS Neglected Tropical Diseases Jul 2022Human brucellosis caused by the facultative intracellular pathogen Brucella spp. is an endemic bacterial zoonosis manifesting as acute or chronic infections with high...
BACKGROUND
Human brucellosis caused by the facultative intracellular pathogen Brucella spp. is an endemic bacterial zoonosis manifesting as acute or chronic infections with high morbidity. Treatment typically involves a combination therapy of two antibiotics for several weeks to months, but despite this harsh treatment relapses occur at a rate of 5-15%. Although poor compliance and reinfection may account for a fraction of the observed relapse cases, it is apparent that the properties of the infectious agent itself may play a decisive role in this phenomenon.
METHODOLOGY/PRINCIPAL FINDINGS
We used B. abortus carrying a dual reporter in a macrophage infection model to gain a better understanding of the efficacy of recommended therapies in cellulo. For this we used automated fluorescent microscopy as a prime read-out and developed specific CellProfiler pipelines to score infected macrophages at the population and the single cell level. Combining microscopy of constitutive and induced reporters with classical CFU determination, we quantified the protective nature of the Brucella intracellular lifestyle to various antibiotics and the ability of B. abortus to persist in cellulo despite harsh antibiotic treatments.
CONCLUSION/SIGNIFICANCE
We demonstrate that treatment of infected macrophages with antibiotics at recommended concentrations fails to fully prevent growth and persistence of B. abortus in cellulo, which may be explained by a protective nature of the intracellular niche(s). Moreover, we show the presence of bona fide intracellular persisters upon antibiotic treatment, which are metabolically active and retain the full infectious potential, therefore constituting a plausible reservoir for reinfection and relapse. In conclusion, our results highlight the need to extend the spectrum of models to test new antimicrobial therapies for brucellosis to better reflect the in vivo infection environment, and to develop therapeutic approaches targeting the persister subpopulation.
Topics: Anti-Bacterial Agents; Brucella abortus; Brucellosis; Humans; Macrophages; Reinfection
PubMed: 35881641
DOI: 10.1371/journal.pntd.0010635