Antibiotic Potentiation Through Phytochemical-Based Efflux Pump Inhibitors to Combat Multidrug Resistance Bacteria.

BACKGROUND: Antimicrobial resistance development poses a significant danger to the efficacy of antibiotics, which were once believed to be the most efficient method for treating infections caused by bacteria. Antimicrobial resistance typically involves various mechanisms, such as drug inactivation or modification, drug target modification, drug uptake restriction, and drug efflux, resulting in decreased antibiotic concentrations within the cell. Antimicrobial resistance has been associated with efflux Pumps, known for their capacity to expel different antibiotics from the cell non-specifically. This makes EPs fascinating targets for creating drugs to combat antimicrobial resistance (AMR). The varied structures of secondary metabolites (phytomolecules) found in plants have positioned them as a promising reservoir of efflux pump inhibitors. These inhibitors act as modifiers of bacterial resistance and facilitate the reintroduction of antibiotics that have lost clinical effectiveness. Additionally, they may play a role in preventing the emergence of multidrug resistant strains. OBJECTIVE: The objective of this review article is to discuss the latest studies on plant-based efflux pump inhibitors such as terpenoids, alkaloids, flavonoids, glycosides, and tetralones. It highlighted their potential in enhancing the effectiveness of antibiotics and combating the development of multidrug resistance. strains. RESULTS: Efflux pump inhibitors (EPIs) derived from botanical sources, including compounds like lysergol, chanaoclavine, niazrin, 4-hydroxy-α-tetralone, ursolic acid, phytol, etc., as well as their partially synthesized forms, have shown significant potential as practical therapeutic approaches in addressing antimicrobial resistance caused by efflux pumps. Further, several phyto-molecules and their analogs demonstrated superior potential for reversing drug resistance, surpassing established agents like reserpine, niaziridin, etc. strains. CONCLUSION: This review found that while the phyto-molecules and their derivatives did not possess notable antimicrobial activity, their combination with established antibiotics significantly reduced their minimum inhibitory concentration (MIC). Specific molecules, such as chanaoclavine and niaziridin, exhibited noteworthy potential in reversing the effectiveness of drugs, resulting in a reduction of the MIC of tetracycline by up to 16 times against the tested strain of bacteria. These molecules inhibited the efflux pumps responsible for drug resistance and displayed a stronger affinity for membrane proteins. By employing powerful EPIs, these molecules can selectively target and obstruct drug efflux pumps. This targeted approach can significantly augment the strength and efficacy of older antibiotics against various drug resistant bacteria, given that active drug efflux poses a susceptibility for nearly all antibiotics.

Effect of electron-phonon coupling on the transport properties of monolayers of ZrS2, BiI3 and PbI2: a thermoelectric perspective.

Thermoelectric materials are used for the conversion of waste heat to electrical energy. The transport coefficients that determine their thermoelectric properties depend on the band structure and the relaxation time of the charge carriers. Both of these are significantly affected by electron-phonon coupling. In this work, using a combination of density functional theory and semiclassical Boltzmann transport theory, we have studied the effect of electron-phonon coupling in monolayers of ZrS2, BiI3 and PbI2. Our results show that in these ionic materials charge carriers are primarily scattered by the optical modes that strongly couple with them. From our study it is conclusively shown that neglecting the contributions of optical modes to electron-phonon coupling in these low-dimensional ionic solids, as is usually done in the computation of relaxation time from deformation theory, results in severe overestimation of the relaxation time. In particular, neglecting the scattering of the optical phonons results in about two orders of magnitude overestimation of relaxation times in these materials. Moreover, we also find that the renormalization of the band structure not only results in the reduction of band gaps but also changes the band dispersion, which strongly affect different transport properties like the electrical conductivity and Seebeck coefficient. Amongst these three materials, we observe that carrier relaxation time due to electron-phonon scattering is reduced as the ionicity of the material decreases.

Attitude among dental practioners towards use of rotary instruments and hand instruments for root canal treatment: a comparative study

Aim: The purpose of present study is to assess the attitude of general dental practioners towards use rotary instruments and hand instruments for root canal treatment. Material and Methods: It was a cross-sectional questionnaire study conducted in the private clinics in Lucknow city, Uttar Pradesh. A total of 400 clinics were visited and face to face interview schedule was conducted. Questionnaire consists of demographic details of dental professionals. Information regarding the years of experience, OPD details and number of root canal treatment done per week by dental professionals was obtained. Use of rotary and hand instruments by dental professionals was inquired. Years of experience with Rotary instruments, procedural problems with rotary instruments faced by dental professionals and reasons for not using the rotary instruments if any was also recorded. Results: 102 (33%) of the total study samples were using rotary instruments for root canal treatment and 100 (32%) using both rotary and hand instruments for root canal treatment. Dentists who are using rotary instruments are facing the procedural problem of file breakage {70 (36%)}. And those dental professionals using hand instruments are facing the problem of ledge formation {82(40%)}. Conclusions: The main procedural failure of the rotary instruments in root canal treatment, faced by dental professionals was file breakage and with hand instrument is ledge formation. Lack of expertise is the main reason which restricts dental professionals from using rotary instruments.

Study of root canal morphology of mandibular premolars in an indian population

AIM: The purpose of this study was to describe the external and internal anatomy of the mandibular premolars. MATERIAL AND METHODS: 100 extracted human permanent mandibular first and second premolars teeth were collected. The length of the tooth from the cusp tip to root apex was measured with the help of Vernier calliper. In case of curved roots, ligature wire was adapted to the root and then straightened and measured. Each tooth was examined for the number of roots, curvature of root, presence of root canal invagination. India ink was injected into the pulp chamber through the access opening with a no.27 gauge needle mounted on a disposable syringe. The ink was then drawn through the root canal system by applying negative pressure to the apical end of tooth with the use of central suction system. RESULTS: The average (mean) length of mandibular first premolar was 22.25 mm. Average (mean) length of mandibular second premolar was 21.90 mm. Mandibular first premolar had a ribbon shaped root canal orifice in 35% of teeth. Mandibular second premolar had a ribbon shaped of root canal orifice in 44% teeth. Mesial invagination of the root was found in 18% of first and 8% second mandibular premolar teeth. 78% had a Type I canal pattern with Type II, Type IV, Type V, Type VI and Type VII canals being identified in 1%, 2%, 13%, 2% and 1% of the teeth respectively. CONCLUSIONS: Complex root canal anatomy frequently found with mandibular premolars among which more common with mandibular first premolars in Indian population.