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Fulltext The Missing Piece: Recent Approaches Investigating the Antimicrobial Mode of Action of Essential Oils

Yang SK, Tan NP, Chong CW, Abushelaibi A, Lim SH, Lai KS

Evol Bioinform Online, 2021;17:1176934320938391.
PMID: 34017165 DOI: 10.1177/1176934320938391

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.
Fulltext Disruption of KPC-producing Klebsiella pneumoniae membrane via induction of oxidative stress by cinnamon bark (Cinnamomum verum J. Presl) essential oil

Yang SK, Yusoff K, Ajat M, Thomas W, Abushelaibi A, Akseer R, et al.

PLoS One, 2019;14(4):e0214326.
PMID: 30939149 DOI: 10.1371/journal.pone.0214326

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.
Current molecular approach for diagnosis of MRSA: a meta-narrative review

Xing SY, Wei LQ, Abushelaibi A, Lai KS, Lim SHE, Maran S

Drug Target Insights, 2022;16:88-96.
PMID: 36761068 DOI: 10.33393/dti.2022.2522

INTRODUCTION:: Detection and diagnosis of methicillin-resistant Staphylococcus aureus (MRSA) are important in ensuring a correct and effective treatment, further reducing its spread. A wide range of molecular approaches has been used for the diagnosis of antimicrobial resistance (AMR) in MRSA. This review aims to study and appraise widely used molecular diagnostic methods for detecting MRSA.
METHODS:: This meta-narrative review was performed by searching PubMed using the following search terms: (molecular diagnosis) AND (antimicrobial resistance) AND (methicillin-resistant Staphylococcus aureus). Studies using molecular diagnostic techniques for the detection of MRSA were included, while non-English language, duplicates and non-article studies were excluded. After reviewing the libraries and a further manual search, 20 studies were included in this article. RAMESES publication standard for narrative reviews was used for this synthesis.
RESULTS:: A total of 20 full papers were reviewed and appraised in this synthesis, consisting of PCR technique (n = 7), deoxyribonucleic acid (DNA) Microarray (n = 1), DNA sequencing (n = 2), Xpert MRSA/SA BC assay (n = 2), matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) (n = 2), MLST (n = 4), SCCmec typing (n = 1) and GENECUBE (n = 1).
DISCUSSION:: Different diagnostic methods used to diagnose MRSA have been studied in this review. This study concludes that PCR has been extensively used due to its higher sensitivity and cost-effectiveness in the past five years
Fulltext Terpene Derivatives as a Potential Agent against Antimicrobial Resistance (AMR) Pathogens

Mahizan NA, Yang SK, Moo CL, Song AA, Chong CM, Chong CW, et al.

Molecules, 2019 Jul 19;24(14).
PMID: 31330955 DOI: 10.3390/molecules24142631

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.
Fulltext Lavender essential oil induces oxidative stress which modifies the bacterial membrane permeability of carbapenemase producing Klebsiella pneumoniae

Yang SK, Yusoff K, Thomas W, Akseer R, Alhosani MS, Abushelaibi A, et al.

Sci Rep, 2020 01 21;10(1):819.
PMID: 31964900 DOI: 10.1038/s41598-019-55601-0

Misuse of antibiotics in the clinical and agricultural sectors has caused the emergence of multidrug-resistant (MDR) Klebsiella pneumoniae which contributes a threat to human health. In this study, we assessed the feasibility of lavender essential oil (LVO) as an antimicrobial agent in combinatory therapy with meropenem in suppressing the growth of carbapenemase-producing K. pneumoniae (KPC-KP). Synergistic interactions between LVO and meropenem were detected, which significantly reduce the inhibitory concentration of both LVO and meropenem by 15 and 4-fold respectively. Comparative proteomic profiling identified a disruption in the bacterial membrane via oxidative stress that was indicated by loss of membrane and cytoplasmic proteins and the upregulation of oxidative regulators. As a proof of concept, zeta potential measurements showed a change in cell surface charge while outer membrane permeability measurement indicated an increase in membrane permeability following exposure to LVO. This was indicative of a disrupted outer membrane. Ethidium bromide influx/efflux assays demonstrated no significant efflux pump inhibition by LVO, and scanning electron microscopy revealed irregularities on the cell surface after exposure to LVO. Oxidative stress was also detected with increased level of ROS and lipid peroxidation in LVO-treated cells. In conclusion, our data suggest that LVO induced oxidative stress in K. pneumoniae which oxidizes the outer membrane, enabling the influx of generated ROS, LVO and meropenem into the bacterial cells, causing damage to the cells and eventually death.
Mechanisms of Antimicrobial Resistance (AMR) and Alternative Approaches to Overcome AMR

Moo CL, Yang SK, Yusoff K, Ajat M, Thomas W, Abushelaibi A, et al.

Curr Drug Discov Technol, 2020;17(4):430-447.
PMID: 30836923 DOI: 10.2174/1570163816666190304122219

Antimicrobials are useful compounds intended to eradicate or stop the growth of harmful microorganisms. The sustained increase in the rates of antimicrobial resistance (AMR) worldwide is worrying and poses a major public health threat. The development of new antimicrobial agents is one of the critical approaches to overcome AMR. However, in the race towards developing alternative approaches to combat AMR, it appears that the scientific community is falling behind when pitched against the evolutionary capacity of multi-drug resistant (MDR) bacteria. Although the "pioneering strategy" of discovering completely new drugs is a rational approach, the time and effort taken are considerable, the process of drug development could instead be expedited if efforts were concentrated on enhancing the efficacy of existing antimicrobials through: combination therapies; bacteriophage therapy; antimicrobial adjuvants therapy or the application of nanotechnology. This review will briefly detail the causes and mechanisms of AMR as background, and then provide insights into a novel, future emerging or evolving strategies that are currently being evaluated and which may be developed in the future to tackle the progression of AMR.
Fulltext Biochemical Composition and Biological Activities of Date Palm (Phoenix dactylifera L.) Seeds: A Review

Alkhoori MA, Kong AS, Aljaafari MN, Abushelaibi A, Erin Lim SH, Cheng WH, et al.

Biomolecules, 2022 Nov 03;12(11).
PMID: 36358976 DOI: 10.3390/biom12111626

Date palm (Phoenix dactylifera L.) is an essential agricultural crop in most Middle Eastern countries, and its fruit, known as dates, is consumed by millions of people. Date seeds, a by-product of the date fruit processing industry, are a waste product used as food for domestic farm animals. Date seeds contain abundant sources of carbohydrates, oil, dietary fiber, and protein; they also contain bioactive phenolic compounds that may possess potential biological properties. In addition, its rich chemical composition makes date seeds suitable for use in food product formulation, cosmetics, and medicinal supplements. This review aims to provide a discourse on the nutritional value of date seeds. The latest data on the cytotoxicity of date seed compounds against cancer cell lines, its ability to combat diabetes, antioxidant potential, antimicrobial effect, and anti-inflammatory activity will be provided, considering its potential to be a nutritional therapeutic agent for chronic diseases. Application of date seeds in the form of powder and oil will also be discussed.
Fulltext Identification of NRAS Diagnostic Biomarkers and Drug Targets for Endometrial Cancer-An Integrated in Silico Approach

Alessandro L, Low KE, Abushelaibi A, Lim SE, Cheng WH, Chang SK, et al.

Int J Mol Sci, 2022 Nov 18;23(22).
PMID: 36430761 DOI: 10.3390/ijms232214285

The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6−33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathological diagnosis and 6% of postmenopausal women with non-diagnostic specimens are later discovered to have severe endometrial lesions. Thus, identifying diagnostic biomarkers could offer a non-invasive diagnosis for community or home-based triage of symptomatic or asymptomatic women. Herein, this study identified high-risk pathogenic nsSNPs in the NRAS gene. The nsSNPs of NRAS were retrieved from the NCBI database. PROVEAN, SIFT, PolyPhen-2, SNPs&GO, PhD-SNP and PANTHER were used to predict the pathogenicity of the nsSNPs. Eleven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MutPred 2 indicated eight nsSNPs to cause decreased stability (DDG scores < −0.5). Post-translational modification and protein−protein interactions (PPI) analysis showed putative phosphorylation sites. The PPI network indicated a GFR-MAPK signalling pathway with higher node degrees that were further evaluated for drug targets. The P34L, G12C and Y64D showed significantly lower binding affinity towards GTP than wild-type. Furthermore, the Kaplan−Meier bioinformatics analyses indicated that the NRAS gene deregulation affected the overall survival rate of patients with endometrial cancer, leading to prognostic significance. Findings from this could be considered novel diagnostic and therapeutic markers.
Fulltext An Overview of the Potential Therapeutic Applications of Essential Oils

Aljaafari MN, AlAli AO, Baqais L, Alqubaisy M, AlAli M, Molouki A, et al.

Molecules, 2021 Jan 26;26(3).
PMID: 33530290 DOI: 10.3390/molecules26030628

The emergence of antimicrobial resistance (AMR) has urged researchers to explore therapeutic alternatives, one of which includes the use of natural plant products such as essential oils (EO). In fact, EO obtained from clove, oregano, thymus, cinnamon bark, rosemary, eucalyptus, and lavender have been shown to present significant inhibitory effects on bacteria, fungi, and viruses; many studies have been done to measure EO efficacy against microorganisms. The strategy of combinatory effects via conventional and non-conventional methods revealed that the combined effects of EO-EO or EO-antibiotic exhibit enhanced efficacy. This paper aims to review the antimicrobial effects of EO, modes of EO action (membrane disruption, efflux inhibition, increase membrane permeability, and decrease in intracellular ATP), and their compounds' potential as effective agents against bacteria, fungi, and viruses. It is hoped that the integration of EO applications in this work can be used to consider EO for future clinical applications.