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Drugs in R&D Jun 2022Lysins are bacteriophage-derived enzymes that degrade essential components of bacteria. Exebacase (Lysin CF-301) is an attractive antimicrobial agent because it... (Review)
Review
Lysins are bacteriophage-derived enzymes that degrade essential components of bacteria. Exebacase (Lysin CF-301) is an attractive antimicrobial agent because it demonstrates rapid bacteriolytic activity against staphylococcal species, including Staphylococcus aureus, has a low resistance profile, eradicates biofilms, and acts synergistically with other antibiotics. Combinations including exebacase and standard of care antibiotics represent an alternative to antibiotic monotherapies currently used to treat invasive staphylococcal infections. This manuscript reviews what is known about exebacase and explores how this novel agent may be used in the future to treat human bacterial pathogens.
Topics: Anti-Bacterial Agents; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35175568
DOI: 10.1007/s40268-022-00383-6 -
International Journal of Biological... Mar 2024Chitosan is a versatile biocompatible polysaccharide which has attracted great attention for gel synthesis. Its reducing character is specifically exploited for...
Chitosan is a versatile biocompatible polysaccharide which has attracted great attention for gel synthesis. Its reducing character is specifically exploited for nanoparticle synthesis via green approach. A silver nanocomposite synthesized using this gel, with a novel gelling agent 2,4,6-trihydroxy benzaldehyde, was found to be a promising candidate for several applications including anti-bacterial, anti-biofilm and anti-oxidant activity as well as catalysis. The nanocomposite was well characterized using various spectroscopic and microscopic techniques such as IR, TGA, XRD, XPS, SEM and TEM. The nanocomposite exhibited high bactericidal activity against both S. aureus and E. coli. Further, it was evaluated for anti-biofilm forming property and its potency as antioxidant agent. The nanocomposite served as a catalyst for degradation of Methyl Orange and Rhodamine B at high concentrations (in the range of mM) with a catalytic efficiency of 98.58 % and 99.56 % within 3 min and 5 min respectively.
Topics: Silver; Antioxidants; Chitosan; Metal Nanoparticles; Staphylococcus aureus; Escherichia coli; Anti-Bacterial Agents; Catalysis; Nanocomposites; Microbial Sensitivity Tests
PubMed: 38320641
DOI: 10.1016/j.ijbiomac.2024.129968 -
Current Microbiology Dec 2023Drug efflux pumps contribute to bacterial multidrug resistance (MDR), reducing antibiotic effectiveness and causing treatment failures. Besides their role in MDR, efflux...
Drug efflux pumps contribute to bacterial multidrug resistance (MDR), reducing antibiotic effectiveness and causing treatment failures. Besides their role in MDR, efflux pumps also assist in the transportation of quorum sensing (QS) signal molecules and increased the tolerance of biofilms. Recently, the search for efflux pump inhibitors from natural sources, including anti-infective plants, has gained attention as a potential therapy against drug-resistant bacteria. In this study, 19 traditional Indian medicinal plants were screened for their efflux pump inhibitory activity against Escherichia coli TGI. The promising extract, i.e., Punica granatum was subsequently fractioned in the solvents of increasing polarity. Among them, at sub-MIC active EPI fraction was PGEF (P. granatum ethyl acetate fraction), further investigated for anti-infective potential against Chromobacterium violaceum 12,472, Pseudomonas aeruginosa PAO1, and Serratia marcescens MTCC 97. PGEF was also evaluated for in vivo efficacy in Caenorhabditis elegans model. Major phytocompounds were analyzed by mass spectroscopic techniques. At respective Sub-MIC, PGEF reduced violacein production by 71.14% in C. violaceum 12,472. Moreover, PGEF inhibited pyocyanin (64.72%), pyoverdine (48.17%), protease (51.35%), and swarming motility (44.82%) of P. aeruginosa PAO1. Furthermore, PGEF reduced the production of prodigiosin and exoprotease by 64.73% and 61.80%, respectively. Similarly, at sub-MIC, PGEF inhibited (≥ 50%) biofilm development in all test pathogens. The key phytocompounds detected in active fraction include 5-hydroxymethylfurfural, trans-p-coumaric acid 4- glucoside, (-)-Epicatechin 3'-O-glucuronide, and ellagic acid. Interestingly, PGEF also demonstrated anti-infective efficacy against the PAO1-infected C. elegans test model and highlighting its therapeutic potential as an anti-infective agent to combat drug-resistant problems.
Topics: Animals; Pomegranate; Plant Extracts; Caenorhabditis elegans; Quorum Sensing; Biofilms; Anti-Bacterial Agents; Bacteria; Pseudomonas aeruginosa; Chromobacterium; Virulence Factors
PubMed: 38151670
DOI: 10.1007/s00284-023-03572-x -
Nano Letters May 2022Nanomaterials usually kill bacteria via multiple mechanisms which are not explicit to the same degree as those of conventional antibiotics. This situation may hinder the...
Nanomaterials usually kill bacteria via multiple mechanisms which are not explicit to the same degree as those of conventional antibiotics. This situation may hinder the development of novel nanoscale antibiotics. Here, we present aminophenol (AP) to modify gold nanoparticles (AP_Au NPs) which show a broad antibacterial spectrum and potent antibacterial effects against multidrug-resistant (MDR) bacteria with clear antibacterial mechanisms. AP_Au NPs can not only damage bacterial cell walls but also bind to the 16S rRNA to block bacterial protein synthesis. Moreover, AP_Au NPs show excellent performance in curing abdominal bacterial infections in an model. AP_Au NPs thus have the potential to become a novel antibacterial agent for clinical applications.
Topics: Aminophenols; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Gold; Humans; Metal Nanoparticles; Microbial Sensitivity Tests; RNA, Ribosomal, 16S
PubMed: 35486905
DOI: 10.1021/acs.nanolett.1c04968 -
Journal of Ethnopharmacology Jan 2022Canarium album Raeusch. belongs to the Burseraceae family. Its ripe fruits, known as Qing Guo (QG) in Traditional Chinese Medicine (TCM), are used to treat sore throat,...
ETHNOPHARMACOLOGICAL RELEVANCE
Canarium album Raeusch. belongs to the Burseraceae family. Its ripe fruits, known as Qing Guo (QG) in Traditional Chinese Medicine (TCM), are used to treat sore throat, cough, and fish or crab poisoning. QG was reported to have antibacterial activity, and it exerted excellent anti-Helicobacter pylori (H. pylori) activity in our screening of abundant TCM. However, few studies have reported its anti-H. pylori activity and mechanism.
AIM OF STUDY
The commonly used eradication therapies for H. pylori infection are antibiotic-based therapies. With the increasing antibiotic resistance of H. pylori, interest in finding alternative therapies has been aroused. This study investigated the phytochemistry profile, in vitro anti-H. pylori activity and possible anti-bacterial mechanism of QG extracts.
MATERIALS AND METHODS
QG extracts were obtained by heat reflux extraction, ultrasonic extraction or liquid-liquid extraction with different solvents. The quantitative and qualitative phytochemical analyses were performed by colorimetric determination, high-performance liquid chromatography (HPLC), and UPLC-electrospray ionization mass spectrometry (ESI-MS). In vitro anti- H. pylori activity was assessed by broth micro-dilution method. Mechanism of action studies included morphological observation using electron microscopy, urease inhibition assay and determination of expression of virulence genes by RT-qPCR.
RESULTS
All QG extracts especially ethyl acetate extract (QGEAE) were rich in phenolic components, with the minimum inhibitory concentrations (MICs) on H.pylori of 39-625 μg/ml and minimum bactericidal concentrations (MBCs) of 78-1250 μg/ml. Both aqueous extract (QGAE) and QGEAE could induce the morphological and structural changes of H. pylori, inhibit urease activity with IC of 1093 μg/ml and 332.90 μg/ml, respectively, and down-regulate the virulence genes, such as vacA and cagA.
CONCLUSIONS
QG may exhibit in vitro anti-H. pylori activity by inhibiting growth, destroying the bacterial structure and down-regulating the expression of virulence factors. Moreover, QG is the homology of food and TCM, which can be considered as a safe and convenient agent against H. pylori infection.
Topics: Anti-Bacterial Agents; Burseraceae; Fruit; Helicobacter Infections; Helicobacter pylori; Inhibitory Concentration 50; Microbial Sensitivity Tests; Plant Extracts
PubMed: 34464702
DOI: 10.1016/j.jep.2021.114578 -
Journal of Enzyme Inhibition and... Dec 2019Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they...
Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they also show antimicrobial activity against the gastric pathogen EZA showed the highest activity, and was effective against clinical isolates resistant to metronidazole, clarithromycin, and/or amoxicillin, suggesting that EZA kills mechanisms different from that of these antibiotics. The frequency of single-step spontaneous resistance acquisition by was less than 5 × 10, showing that resistance to EZA does not develop easily. Resistance was associated with mutations in three genes, including the one that encodes undecaprenyl pyrophosphate synthase, a known target of sulphonamides. The data indicate that EZA impacts multiple targets in killing . Our findings suggest that developing the approved anti-glaucoma drug EZA into a more effective anti- agent may offer a faster and cost-effective route towards new antimicrobials with a novel mechanism of action.
Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Ethoxzolamide; Helicobacter pylori; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship
PubMed: 31530039
DOI: 10.1080/14756366.2019.1663416 -
Biofouling Jan 2022Plasma-initiated free radical polymerization was used to engineer carbon nanoparticles (CNPs) with tailored chemical and physical properties. Following surface...
Plasma-initiated free radical polymerization was used to engineer carbon nanoparticles (CNPs) with tailored chemical and physical properties. Following surface modification, CNPs were loaded with a highly effective anti-infection agent called metal-free Russian propolis ethanol extract (MFRPEE), thus, creating nano-based drug delivery systems (NBDDSs). The loading of MFRPEE onto grafted CNPs occurred naturally through both electrostatic interactions and hydrogen bonding. When constructed under optimal experimental conditions, the NBDDSs were stable under physiologic conditions, and demonstrated enhanced anti-biofilm activity when compared with free MFRPEE. Mechanistic studies revealed that the enhanced anti-infectious activity of the NBDDSs was attributed to the modified surface chemistry of grafted CNPs. More specifically, the overall positive surface charge on grafted CNPs, which stems from quaternary ammonium polymer brushes covalently bound to the CNPs, provides NBDDSs with the ability to specifically target negatively charged components of biofilms. When studying the release profile of MFRPEE from the modified CNPs, acidic components produced by a biofilm triggered the release of MFRPEE bound to the NBDDS. Once in its free form, the anti-infectious properties of MFRPEE became activated and damaged the extracellular polymeric matrix (EPM) of the biofilm. Once the architecture of the biofilm became compromised, the EPM was no longer capable of protecting the bacteria encapsulated within the biofilm from the anti-infectious agent. Consequently, exposure of bacteria to MFRPEE led to bacterial cell death and biofilm inactivation. The results obtained from this study begin to examine the potential application of NBDDSs for the treatment of healthcare-associated infections (HCAIs).
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Biofilms; Carbon; Drug Delivery Systems; Nanoparticle Drug Delivery System; Nanoparticles; Polymerization; Polymers; Propolis
PubMed: 34839780
DOI: 10.1080/08927014.2021.2008376 -
Letters in Applied Microbiology Sep 2022Marine micro-organisms are a promising source for novel natural compounds with many medical and biotechnological applications. Here, we demonstrate limitations and... (Review)
Review
Marine micro-organisms are a promising source for novel natural compounds with many medical and biotechnological applications. Here, we demonstrate limitations and recent strategies for investigating the marine microbial community for novel bioactive metabolites, specifically those of antimicrobial potential. These strategies include culture-dependent methods such as modifying the standard culture media, including changing the gelling agent, dissolving vehicle, media supplementation and preparation to access a broader range of bacterial diversity from marine samples. Furthermore, we discuss strategies such as in situ cultivation, dilution-to-extinction cultivation and long-term incubation. We are presenting recent applications of culture-independent methods such as genome mining, proteomics profiling and the application of metagenomics as a novel strategy for structure confirmation in the discovery of the marine micro-organism for novel antimicrobial metabolites. We present this review as a simple guide and a helpful resource for those who seek to enter the challenging field of applied marine microbiology.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Aquatic Organisms; Bacteria; Biological Products; Culture Media; Metagenomics
PubMed: 35485872
DOI: 10.1111/lam.13728 -
Recenti Progressi in Medicina Jan 2023Due to the worry growing increase in bacterial antibiotic resistance and the scanty availability of new antibiotics, it is highly recommended to use not recently...
Due to the worry growing increase in bacterial antibiotic resistance and the scanty availability of new antibiotics, it is highly recommended to use not recently synthesized, but still active molecules. Clofoctol is a synthetic chemotherapeutic agent with a different mechanism of action, as compared with the other antibacterial molecules currently available. By reducing intracellular ATP, clofoctol inhibits the synthesis of bacterial cytoplasmic membrane peptidoglycans, inducing the arrest of cell wall synthesis, thus characterizing the molecule as a "membrane-acting agent". More recently, however, it has been shown that clofoctol is also able to induce apoptosis by inhibiting the translation of intracellular proteins. An important property of clofoctol is the rapidity of the antimicrobial effect, which allows the complete eradication of the pathogen and makes the development of resistance unlikely. Administered rectally, the drug rapidly accumulates in the tissues. Most of the clinical studies conducted on clofoctol concern the treatment of respiratory diseases in children. The drug appears to be more active in upper rather than in lower respiratory tract infections. Tolerability was reported to be good, with a low incidence of side effects.
Topics: Child; Humans; Anti-Bacterial Agents; Cresols; Chlorobenzenes; Bacteria
PubMed: 36621918
DOI: 10.1701/3943.39256 -
The Journal of Antimicrobial... Nov 2021Staphylococcus aureus - a major aetiological agent of bone and joint infection (BJI) - is associated with a high risk of relapse and chronicity, in part due to its... (Review)
Review
Staphylococcus aureus - a major aetiological agent of bone and joint infection (BJI) - is associated with a high risk of relapse and chronicity, in part due to its ability to invade and persist in non-professional phagocytic bone cells such as osteoblasts. This intracellular reservoir protects S. aureus from the action of the immune system and most antibiotics. To date, the choice of antimicrobial strategies for BJI treatment mostly relies on standard susceptibility testing, bone penetration of antibiotics and their 'antibiofilm' activity. Despite the role of intracellular persistent S. aureus in the development of chronic infection, the ability of antibiotics to target the S. aureus intraosteoblastic reservoir is not considered in therapeutic choices but might represent a key determinant of treatment outcome. This review provides an overview of the intracellular pharmacokinetics of antistaphylococcal drugs used in the treatment of BJI and of their ability to target intraosteoblastic S. aureus. Thirteen studies focusing on the intraosteoblastic activity of antibiotics against S. aureus were reviewed, all relying on in vitro models of osteoblast infection. Despite varying incubation times, multiplicities of infection, bacterial strains, and the types of infected cell lines, rifamycins and fluoroquinolones remain the two most potent antimicrobial classes for intraosteoblastic S. aureus eradication, consistent with clinical data showing a superiority of this combination therapy in S. aureus orthopaedic device-related infections.
Topics: Anti-Bacterial Agents; Humans; Persistent Infection; Rifamycins; Staphylococcal Infections; Staphylococcus aureus
PubMed: 34459881
DOI: 10.1093/jac/dkab301