Search

Antibiotic resistance is a major global health issue that has seen alarming rates of increase in all parts of the world over the past two decades. The surge in antibiotic resistance has resulted in longer hospital stays, higher medical costs, and elevated mortality rates. Constant attempts have been made to discover newer and more effective antimicrobials to reduce the severity of antibiotic resistance. Plant secondary metabolites, such as essential oils, have been the major focus due to their complexity and bioactive nature. However, the underlying mechanism of their antimicrobial effect remains largely unknown. Understanding the antimicrobial mode of action of essential oils is crucial in developing potential strategies for the use of essential oils in a clinical setting. Recent advances in genomics and proteomics have enhanced our understanding of the antimicrobial mode of action of essential oils. We might well be at the dawn of completing a mystery on how essential oils carry out their antimicrobial activities. Therefore, an overview of essential oils with regard to their antimicrobial activities and mode of action is discussed in this review. Recent approaches used in identifying the antimicrobial mode of action of essential oils, specifically from the perspective of genomics and proteomics, are also synthesized. Based on the information gathered from this review, we offer recommendations for future strategies and prospects for the study of essential oils and their function as antimicrobials. [ABSTRACT FROM AUTHOR]

Background: Clinacanthus nutans (CN) is a small shrub native to tropical Asia known for their anti-oxidant, anti-inflammation, anti-cancer, and anti-viral activities. Objectives: This study aimed to investigate the effect of CN extract on human embryonic kidney cell line (HEK-Blue™-4) in a proteomic perspective. Materials and Methods: Comparative proteomic profiling through two-dimensional sodium dodecyl sulfate gel electrophoresis was performed on HEK-Blue™-4 treated with CN leaf polar extract. Results: We successfully identified seven upregulated proteins, of which five promoted the growth of the HEK-Blue™-4 cells. Interestingly, a potent antioxidant enzyme which neutralizes reactive oxygen or nitrogen species, peroxiredoxin-1 was also upregulated in HEK-Blue™-4 cell lines after treatment with CN leaf polar extract. Conclusion: CN leaf polar extract promotes the growth of HEK-Blue™-4 cells and induced the expression of peroxiredoxin-1, which protects the cells from reactive oxygen species during the inflammation process. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae (KP) remains the most prevalent nosocomial pathogen and carries the carbapenemase (KPC) gene which confers resistance towards carbapenem. Thus, it is necessary to discover novel antimicrobials to address the issue of antimicrobial resistance in such pathogens. Natural products such as essential oils are a promising source due to their complex composition. Essential oils have been shown to be effective against pathogens, but the overall mechanisms have yet to be fully explained. Understanding the molecular mechanisms of essential oil towards KPC-KP cells would provide a deeper understanding of their potential use in clinical settings. Therefore, we aimed to investigate the mode of action of essential oil against KPC-KP cells from a proteomic perspective by comparing the overall proteome profile of KPC-KP cells treated with cinnamon bark (Cinnamomum verum J. Presl) essential oil (CBO) at their sub-inhibitory concentration of 0.08% (v/v). A total of 384 proteins were successfully identified from the non-treated cells, whereas only 242 proteins were identified from the CBO-treated cells. Proteins were then categorized based on their biological processes, cellular components and molecular function prior to pathway analysis. Pathway analysis showed that CBO induced oxidative stress in the KPC-KP cells as indicated by the abundance of oxidative stress regulator proteins such as glycyl radical cofactor, catalase peroxidase and DNA mismatch repair protein. Oxidative stress is likely to oxidize and disrupt the bacterial membrane as shown by the loss of major membrane proteins. Several genes selected for qRT-PCR analysis validated the proteomic profile and were congruent with the proteomic abundance profiles. In conclusion, KPC-KP cells exposed to CBO undergo oxidative stress that eventually disrupts the bacterial membrane possibly via interaction with the phospholipid bilayer. Interestingly, several pathways involved in the bacterial membrane repair system were also affected by oxidative stress, contributing to the loss of cells viability. [ABSTRACT FROM AUTHOR]

In this paper, we have demonstrated the optimized device performance in the Γ-shaped gate AlGaN/AlN/GaN metal oxide semiconductor high electron mobility transistor (MOS-HEMT) by incorporating aluminum into atomic layer deposited (ALD) HfO2 and comparing it with the commonly used HfO2 gate dielectric with the N2 surface plasma treatment. The inclusion of Al in the HfO2 increased the crystalline temperature (~1000 °C) of hafnium aluminate (HfAlOX) and kept the material in the amorphous stage even at very high annealing temperature (>800 °C), which subsequently improved the device performance. The gate leakage current (IG) was significantly reduced with the increasing post deposition annealing (PDA) temperature from 300 to 600 °C in HfAlOX-based MOS-HEMT, compared to the HfO2-based device. In comparison with HfO2 gate dielectric, the interface state density (Dit) can be reduced significantly using HfAlOX due to the effective passivation of the dangling bond. The greater band offset of the HfAlOX than HfO2 reduces the tunneling current through the gate dielectric at room temperature (RT), which resulted in the lower IG in Γ-gate HfAlOX MOS-HEMT. Moreover, IG was reduced more than one order of magnitude in HfAlOX MOS-HEMT by the N2 surface plasma treatment, due to reduction of N2 vacancies which were created by ICP dry etching. The N2 plasma treated Γ-shaped gate HfAlOX-based MOS-HEMT exhibited a decent performance with IDMAX of 870 mA/mm, GMMAX of 118 mS/mm, threshold voltage (VTH) of −3.55 V, higher ION/IOFF ratio of approximately 1.8 × 109, subthreshold slope (SS) of 90 mV/dec, and a high VBR of 195 V with reduced gate leakage current of 1.3 × 10−10 A/mm. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance remains one of the most challenging issues that threatens the health of people around the world. Plant-derived natural compounds have received considerable attention for their potential role to mitigate antibiotic resistance. This study was carried out to assess the antimicrobial activity and mode of action of a monoterpene, 1,8-cineol (CN) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Results showed that resazurin microplate assay and time-kill analysis revealed bactericidal effects of CN at 28.83 mg/mL. Zeta potential showed that CN increased the surface charge of bacteria and an increase of outer membrane permeability was also detected. CN was able to cause leakage of proteins and nucleic acids in KPC-KP cells upon exposure to CN and ethidium bromide influx/efflux experiment showed the uptake of ethidium bromide into the cell; this was attributed to membrane damage. CN was also found to induce oxidative stress in CN-treated KPC-KP cells through generation of reactive oxygen species which initiated lipid peroxidation and thus damaging the bacterial cell membrane. Scanning and transmission electron microscopies further confirmed the disruption of bacterial cell membrane and loss of intracellular materials. In this study, we demonstrated that CN induced oxidative stress and membrane damage resulting in KPC-KP cell death. [ABSTRACT FROM AUTHOR]

The evolution of antimicrobial resistance (AMR) in pathogens has prompted extensive research to find alternative therapeutics. Plants rich with natural secondary metabolites are one of the go-to reservoirs for discovery of potential resources to alleviate this problem. Terpenes and their derivatives comprising of hydrocarbons, are usually found in essential oils (EOs). They have been reported to have potent antimicrobial activity, exhibiting bacteriostatic and bactericidal effects against tested pathogens. This brief review discusses the activity of terpenes and derivatives against pathogenic bacteria, describing the potential of the activity against AMR followed by the possible mechanism exerted by each terpene class. Finally, ongoing research and possible improvisation to the usage of terpenes and terpenoids in therapeutic practice against AMR are discussed. [ABSTRACT FROM AUTHOR]

To better understand the synergistic antibacterial activity between piperacillin and Lavandula angustifolia essential oil (LEO) against multidrug-resistant Escherichia coli, we performed microarray transcriptomic analysis of LEO when used alone and in combination with piperacillin against the non-treated control. In total, 90 genes were differentially expressed after the combination of LEO and piperacillin treatment. Among the up-regulated genes, nfsB, nemA, fruA, nfsB, nemA are known to control microbial metabolism and nitrotoluene degradation, which were observed only in the LEO–piperacillin combinatory treatment. Four candidate genes from the microarray result, srIA, srID, waaR and nfsB, were validated by qRT-PCR as these genes showed differential expression consistently in the two methods. Biochemical pathway analysis showed that there was upregulation of genes involved in several biological processes including fructose and mannose metabolism, phosphotransferase system (PTS), lipopolysaccharide biosynthesis and nitrotoluene degradation. Genes involved in microbial metabolism in diverse environments were found both up- and down-regulated in LEO–piperacillin combinatory treatment. Our study provides new information concerning the transcriptional changes that occur during the LEO and piperacillin interaction against the multidrug-resistant bacteria and contributes to unravel the mechanisms underlying this synergism. [ABSTRACT FROM AUTHOR]

Separation of duplicated spindle poles is the first step in forming the mitotic spindle. Kinesin-5 crosslinks and slides anti-parallel microtubules (MTs), but it is unclear how these two activities contribute to the first steps in spindle formation. In this study, we report that in monopolar spindles, the duplicated spindle poles snap apart in a fast and irreversible step that produces a nascent bipolar spindle. Using mutations in Kinesin-5 that inhibit microtubule sliding, we show that the fast, irreversible pole separation is primarily driven by microtubule crosslinking. Electron tomography revealed microtubule pairs in monopolar spindles have short overlaps that intersect at high angles and are unsuited for ensemble Kinesin-5 sliding. However, maximal extension of a subset of anti-parallel microtubule pairs approaches the length of nascent bipolar spindles and is consistent with a Kinesin-5 crosslinking-driven transition. Nonetheless, microtubule sliding by Kinesin-5 contributes to stabilizing the nascent spindle and setting its stereotyped equilibrium length. • The monopolar-to-bipolar spindle transition is fast and irreversible • The fast transition is driven by Cin8 (Kinesin-5) microtubule crosslinking • Nascent bipolar spindles need Kinesin-5 sliding for steady-state lengths >1 μm • Spindle formation sequentially integrates Kinesin-5 MT crosslinking and sliding Leary et al. show that bipolar spindle formation is a fast and irreversible process driven by Kinesin-5 microtubule crosslinking consistent with electron tomography revealing an initial microtubule architecture unsuited to Kinesin-5 sliding. However, Kinesin-5 sliding plays a role in ensuring subsequent bipolar spindle elongation and stability. [ABSTRACT FROM AUTHOR]