Common factors in the mode of action of vancomycin group antibiotics active against resistant bacteria

1997 ◽  
pp. 723-724 ◽  
Author(s):  
Gary J. Sharman ◽  
Dudley H. Williams
Keyword(s):  
Mode Of Action ◽  
Common Factors ◽  
Resistant Bacteria ◽  
Vancomycin Group

scholarly journals Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1620
Author(s):  
Victor Markus ◽  
Karina Golberg ◽  
Kerem Teralı ◽  
Nazmi Ozer ◽  
Esti Kramarsky-Winter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Conformational Changes ◽  
Mode Of Action ◽  
Pathogenic Bacteria ◽  
Molecular Targets ◽  
Resistant Bacteria ◽  
Public Healthcare ◽  
C 30

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.

scholarly journals Cellular Response of the Amoeba Acanthamoeba castellanii to Chlorine, Chlorine Dioxide, and Monochloramine Treatments

2011 ◽  
Vol 77 (14) ◽  
pp. 4974-4980 ◽  
Author(s):  
Emerancienne Mogoa ◽  
Charles Bodet ◽  
Franck Morel ◽  
Marie-Hélène Rodier ◽  
Bernard Legube ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Flow Cytometry ◽  
Chlorine Dioxide ◽  
Mode Of Action ◽  
Cellular Response ◽  
Acanthamoeba Castellanii ◽  
Size Reduction ◽  
Resistant Bacteria ◽  
Free Living ◽  
Content Type

ABSTRACTAcanthamoeba castellaniiis a free-living amoebae commonly found in water systems. Free-living amoebae might be pathogenic but are also known to bear phagocytosis-resistant bacteria, protecting these bacteria from water treatments. The mode of action of these treatments is poorly understood, particularly on amoebae. It is important to examine the action of these treatments on amoebae in order to improve them. The cellular response to chlorine, chlorine dioxide, and monochloramine was tested onA. castellaniitrophozoites. Doses of disinfectants leading to up to a 3-log reduction were compared by flow cytometry and electron microscopy. Chlorine treatment led to size reduction, permeabilization, and retraction of pseudopods. In addition, treatment with chlorine dioxide led to a vacuolization of the cytoplasm. Monochloramine had a dose-dependent effect. At the highest doses monochloramine treatment resulted in almost no changes in cell size and permeability, as shown by flow cytometry, but the cell surface became smooth and dense, as seen by electron microscopy. We show that these disinfectants globally induced size reduction, membrane permeabilization, and morphological modifications but that they have a different mode of action onA. castellanii.

scholarly journals Intra-surgical Site Vancomycin Powder Application in Infected Diabetic Heel Ulcers with Calcaneal Osteomyelitis

2020 ◽  
Vol 5 (4) ◽  
pp. 2473011420S0014
Author(s):  
James D. Brodell ◽  
Irvin Oh
Keyword(s):  
Ankle Brachial Index ◽  
Group Versus ◽  
High Rate ◽  
Resection Margins ◽  
Wound Complications ◽  
Resistant Bacteria ◽  
Diabetic Patients ◽  
Vancomycin Powder ◽  
Vancomycin Group

Category: Diabetes; Hindfoot Introduction/Purpose: The treatment of diabetic heel ulcers (DHU) with osteomyelitis is challenging, and dismal clinical results have been reported after calcanectomy, with reported revision rates of 0-63.5%. The topical application of vancomycin powder has reported to be beneficial in foot and ankle surgery amongst diabetic patients. However, no studies have examined the efficacy of intra-surgical site vancomycin powder application in DHU surgery. There are potential risks of intra-surgical site vancomycin powder application, such as the selection of gram-negative and multi-drug resistant bacteria, and increased wound complications. Thus, we aimed to 1) assess the clinical outcomes of calcanectomy for DHU and 2) investigate the clinical efficacy of intra-surgical site vancomycin powder application in patients who underwent partial- or total calcanectomies performed to treat infected DHU with osteomyelitis. Methods: This study was approved by our institution’s Research Subjects Review Board. Subjects were identified utilizing current procedural terminology code 28120 (Partial excision bone; talus or calcaneus) for partial or total calcanectomies performed at our academic institution. Thirty-eight calcanectomies performed secondary to DHU with osteomyelitis were identified. Patient demographics (age, sex, gender, body mass index), preoperative labs (hemoglobin A1c, blood glucose, white blood cell, erythrocyte sedimentation rate, C-reactive protein, serum creatinine, hemoglobin), ASA Class, peripheral arterial disease assessed by ankle-brachial index, Charleston Comorbidity Index, and intra-surgical site application of vancomycin powder were recorded. Duration of follow-up, type and quantity of systemic antibiotics administered during surgery, surgical complications, and return to the operating room (RTOR) were also recorded. There were two cohorts: those whose surgical wound was closed without vancomycin powder (initial 25 patients; ‘novancomycin’ group) versus those whose surgical site was closed with vancomycin powder (later 13 patients; ‘vancomycin’ group). Results: The average follow-up was 26.1 +- 15.0 months. Surgical pathology confirmed negative bone resection margins for all patients. Nineteen patients required an unplanned RTOR (50.0%). A revision amputation was performed in fifteen extremities (39.5%). Thirteen patients received intrawound vancomycin at closure, and 25 did not. Nine of thirteen (69.2%) patients who received vancomycin powder required RTOR. This includedTwo below-knee amputations (BKA), two irrigation and debridements (I&D), and six revision or total calcanectomies. There was a significantly higher rate of RTOR in the vancomycin cohort relative to the no-vancomycin cohort (76.9% vs 36.0%, p=0.038). Of the 25 no-vancomycin group, 17 did not return to the OR, 4 underwent BKA, 1 had I&D, and 2 required revision or total calcanectomy. Conclusion: In our cohort, calcanectomy performed for the surgical management of DHU with osteomyelitis yielded a high rate (50%) of unplanned follow-up procedures. Intra-surgical site vancomycin powder application during wound closure after calcanectomy did not result in clinical benefit and is likely unnecessary. The risk and benefit profile of intra-surgical site vancomycin powder application for diabetic foot infection surgery needs to be further investigated.

High Affinity Surface Binding of a Strongly Dimerizing Vancomycin-Group Antibiotic to a Model of Resistant Bacteria

1999 ◽  
Vol 121 (22) ◽  
pp. 5259-5265 ◽  
Author(s):  
Dominic P. O'Brien ◽  
Richard M. H. Entress ◽  
Matthew A. Cooper ◽  
Simon W. O'Brien ◽  
Andrew Hopkinson ◽  
...  
Keyword(s):  
Resistant Bacteria ◽  
Surface Binding ◽  
High Affinity ◽  
Vancomycin Group

scholarly journals Mode of action of the 2-phenylquinoline efflux inhibitor PQQ4R againstEscherichia coli

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3168 ◽  
Author(s):  
Diana Machado ◽  
Laura Fernandes ◽  
Sofia S. Costa ◽  
Rolando Cannalire ◽  
Giuseppe Manfroni ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Bacterial Infections ◽  
Efflux Pump ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Synergistic Activity ◽  
Dependent Manner ◽  
Gram Negative ◽  
E Coli ◽  
Efflux Pump Inhibitors

Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4-propoxyphenyl) quinolone – PQQ4R), againstEscherichia coli,by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN) and chlorpromazine (CPZ). The results showed that PQQ4R acts synergistically, in a concentration dependent manner, with antibiotics known to be subject to efflux inE. colireducing their MIC in correlation with the inhibition of their efflux. Real-time fluorometry assays demonstrated that PQQ4R at sub-inhibitory concentrations promote the intracellular accumulation of ethidium bromide inhibiting its efflux similarly to PAβN or CPZ, well-known and described efflux pump inhibitors for Gram-negative bacteria and whose clinical usage is limited by their levels of toxicity at clinical and bacteriological effective concentrations. The time-kill studies showed that PQQ4R, at bactericidal concentrations, has a rapid antimicrobial activity associated with a fast decrease of the intracellular ATP levels. The results also indicated that the mode of action of PQQ4R involves the destabilization of theE. coliinner membrane potential and ATP production impairment, ultimately leading to efflux pump inhibition by interference with the energy required by the efflux systems. At bactericidal concentrations, membrane permeabilization increases and finally ATP is totally depleted leading to cell death. Since drug resistance mediated by the activity of efflux pumps depends largely on the proton motive force (PMF), dissipaters of PMF such as PQQ4R, can be regarded as future adjuvants of conventional therapy againstE. coliand other Gram-negative bacteria, especially their multidrug resistant forms. Their major limitation is the high toxicity for human cells at the concentrations needed to be effective against bacteria. Their future molecular optimization to improve the efflux inhibitory properties and reduce relative toxicity will optimize their potential for clinical usage against multi-drug resistant bacterial infections due to efflux.

Synthesis Ruthenium complexes Functionalized with Benzothiophene and their Antibacterial activity against Staphylococcus aureus

2021 ◽  
Author(s):  
Xiangwen Liao ◽  
lianghong liu ◽  
yanhui Tan ◽  
guijuan jiang ◽  
haihong fang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Mode Of Action ◽  
Antimicrobial Agents ◽  
Ruthenium Complexes ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria

New effective antimicrobial agents with novel mode of action are urgently need due to the continued emergence of drug-resistant bacteria. Here, three ruthenium complexes functionalized with benzothiophene: [Ru(phen)2(BTPIP)](ClO4)2 (Ru(II)-1), [Ru(dmp)2(BTPIP)](ClO4)2...

scholarly journals The effect and mode of action of saponins on the microbial populations and fermentation in the rumen and ruminant production

2009 ◽  
Vol 22 (2) ◽  
pp. 204-219 ◽  
Author(s):  
A. K. Patra ◽  
J. Saxena
Keyword(s):  
Microbial Community ◽  
Mode Of Action ◽  
Rumen Fermentation ◽  
Feed Additives ◽  
Resistant Bacteria ◽  
Systematic Research ◽  
Chemical Additives ◽  
Ammonia Adsorption ◽  
Chemical Structures ◽  
Rumen Metabolism

The growing public concerns over chemical residues in animal-derived foods and threats of antibiotic-resistant bacteria have renewed interest in exploring safer alternatives to chemical feed additives in ruminant livestock. Various bioactive phytochemicals including saponins appear to be potential ‘natural’ alternatives to ‘chemical’ additives in modulating rumen fermentation favourably and animal performance. Saponins are a diverse group of glycosides present in many families of plants. The primary effect of saponins in the rumen appears to be to inhibit the protozoa (defaunation), which might increase the efficiency of microbial protein synthesis and protein flow to the duodenum. Furthermore, saponins may decrease methane production via defaunation and/or directly by decreasing the activities (i.e. rate of methanogenesis or expression of methane-producing genes) and numbers of methanogens. Saponins may also selectively affect specific rumen bacteria and fungi, which may alter the rumen metabolism beneficially or adversely. The ammonia-adsorption and modulation of digesta passage in the rumen by saponins have also been implicated in altering rumen metabolism, but their physiological responses are likely to be negligible compared with microbiological effects. The effects of saponins on rumen fermentation have not been found to be consistent. These discrepancies appear to be related to the chemical structure and dosage of saponins, diet composition, microbial community and adaptation of microbiota to saponins. There is need for systematic research based on chemical structures of saponins, nutrient composition of diets and their effects on rumen microbial ecosystem to obtain consistent results. The present paper reviews and discusses the effects and mode of action of saponins on microbial community and fermentation in the rumen, and ruminant performance.

scholarly journals Mode of Action of Van-M-02, a Novel Glycopeptide Inhibitor of Peptidoglycan Synthesis, in Vancomycin-Resistant Bacteria

2009 ◽  
Vol 54 (2) ◽  
pp. 960-962 ◽  
Author(s):  
Kenji Miura ◽  
Hidenori Yamashiro ◽  
Kouichi Uotani ◽  
Satoshi Kojima ◽  
Takashi Yutsudo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Inhibitory Activity ◽  
Mode Of Action ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Peptidoglycan Synthesis ◽  
Vancomycin Resistant Enterococci ◽  
Resistant Strains ◽  
Vancomycin Resistant

ABSTRACT Van-M-02, a novel glycopeptide, was revealed to exert potent activities against Gram-positive bacteria, including vancomycin-resistant enterococci (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA). A crude assay system was then used to study the mode of action of Van-M-02 as a peptidoglycan synthesis model of both vancomycin-susceptible and -resistant strains. The results suggested that Van-M-02 inhibits the synthesis of lipid intermediates irrespective of their termini. This inhibitory activity may contribute to the anti-VRE and anti-VRSA activities observed.

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