Essential Oils: The Ultimate Solution to Antimicrobial Resistance in <i>Escherichia coli</i>?

Antimicrobial resistance (AMR) is on the rise; the only solution for overcoming this is through accelerated drug discovery. At current, bacterial evolutionary rates is still clearly the undisputed winner in this war. To circumvent this, evolution of resistance need to be curbed and this can only be effective via novel approaches, one of which includes the use of a resistance modifying agent. The criterion to qualify as a resistance modifier necessitates the co-administration of the agent with an inhibitor that deactivates the bacterial resistance mechanism, restoring its original effectiveness. Natural products such as plant extracts and essential oils (EOs) have been viewed as a privileged group for investigation of their potential roles to combat antibiotic resistance, due to their compositions of active chemical compounds. The route for multidrug resistance development in Gram‐negative bacteria is primarily mediated by the sophisticated inner and outer membrane barriers, which function to protect the cell against external toxic compounds; hence, bypass of these bacterial membranes would successfully restore or improve efficacy of the antimicrobials. The aim of this chapter is to concisely describe some examples for recent strategies used in the screening of possible resistance modifiers from essential oils specifically against MDR Escherichia coli

Genomic Insights into Two Colistin-Resistant Klebsiella pneumoniae Strains Isolated from the Stool of Preterm Neonate During the First Week of Life

Background: Klebsiella pneumoniae is a major opportunistic pathogen frequently associated with nosocomial infections, and often poses a major threat to immunocompromised patients. In our previous study, two K. pneumoniae (K36 and B13), which displayed resistance to almost all major antibiotics, including colistin, were isolated. Both isolates were not associated with infection and isolated from the stools of two preterm neonates admitted to the neonatal intensive care unit (NICU) during their first week of life. Materials and Methods: In this study, whole genome sequencing was performed on these two clinical multidrug resistant K. pneumoniae. We aimed to determine the genetic factors that underline the antibiotic-resistance phenotypes of these isolates. Results: The strains harbored blaSHV-27, blaSHV-71, and oqxAB genes conferring resistance to cephalosporins, carbapenems, and fluoroquinolones, respectively, but not harboring any known plasmid-borne colistin resistance determinants such as mcr-1. However, genome analysis discovered interruption of mgrB gene by insertion sequences gaining insight into the development of colistin resistance. Conclusion: The observed finding that points to a scenario of potential gut-associated resistance genes to Gram negative (K. pneumoniae) host in the NICU environment warrants attention and further investigation. © Copyright 2020, Mary Ann Liebert, Inc., publishers 2020

Whole genome analysis of multidrug resistant Citrobacter freundii B9-C2 isolated from preterm neonate’s stool in the first week

Background: Resistance to colistin, the last line therapy for infections caused by multidrug-resistant Gram-negative bacteria represents a major public health threat. Citrobacter freundii B9-C2 which was isolated from the stool of preterm neonate on the first week of life, displayed resistance to almost all major antibiotics, including colistin. Through whole genome sequencing (WGS), we characterised the genome features that underline the antibiotic-resistance phenotype of this isolate. Methods: Genome of C. freundii B9-C2 was sequenced on an Illumina MiSeq platform. The assembled genome was annotated and deposited into GenBank under the accession number CP027849. Results: Multiple antimicrobial resistance genes including blaCMY-66 were identified. Further, the presence of 15 antibiotic efflux pump-encoding resistance genes, including crp, baeR, hns, patA, emrB, msbA, acrA, acrB, emrR, mdtC, mdtB, mdtG, kdpE, mdfA and msrB were detected and likely to account for the observed cephalosporins, carbapenems, aminoglycosides and monobactams resistance in C. freundii B9-C2. The isolate also presented unique virulence genes related to biofilm formation, motility and iron uptake. The genome was compared to publicly available genomes and it was closely related to strains with environmental origins. Conclusion: To the best of our knowledge, this is the first report of intestinal carriage of colistin-resistant C. freundii from the stool of neonate in Malaysia. Using genomic analysis, we have contributed to the understanding of the potential mechanism of resistance and the phylogenetic relationship of the isolates with draft genomes available in the public domain. © 2020 The Author(s

Membrane disruption properties of essential oils—a double-edged sword?

The emerging literature has suggested essential oils (EOs) as new possible weapons to fight antimicrobial resistance due to their inherent antimicrobial properties. However, the potential pharmaceutical use of EOs is confronted by several limitations, including being non-specific in terms of drug targeting, possessing a high cytotoxicity as well as posing a high risk for causing skin irritation. Furthermore, some EOs have been demonstrated to adversely affect the cellular lipid profiles and permeability of the cell membrane, which may result in undesirable outcomes for the cells. Nevertheless, owing to their naturally complex compositions, EOs still hold undiscovered potential to mitigate antimicrobial resistance, as an alternative to existing antibiotics. To address the issue of overuse in antibiotics for crops which have led to the growing threat of antimicrobial resistance globally, EOs have also been proposed as potential biopesticides. Since the perceived advantages of antimicrobial attributes in EOs remain largely unexplored, this review aims to provide a discourse into its current practical usefulness in the agricultural setting. Finally, updated bioengineering techniques with emphasis of the biopesticide potential of EOs as a means to alleviate antimicrobial resistance will be included

MgrB mutations and altered cell permeability in colistin resistance in <i>Klebsiella pneumoniae</i>

There has been a resurgence in the clinical use of polymyxin antibiotics such as colistin due to the limited treatment options for infections caused by carbapenem-resistant Enterobacterales (CRE). However, this last-resort antibiotic is currently confronted with challenges which include the emergence of chromosomal and plasmid-borne colistin resistance. Colistin resistance in Klebsiella pneumoniae is commonly caused by the mutations in the chromosomal gene mgrB. MgrB spans the inner membrane and negatively regulates PhoP phosphorylation, which is essential for bacterial outer membrane lipid biosynthesis. The present review intends to draw attention to the role of mgrB chromosomal mutations in membrane permeability in K. pneumoniae that confer colistin resistance. With growing concern regarding the global emergence of colistin resistance, deciphering physical changes of the resistant membrane mediated by mgrB inactivation may provide new insights for the discovery of novel antimicrobials that are highly effective at membrane penetration, in addition to finding out how this can help in alleviating the resistance situation

Plant-derived antimicrobials: insights into mitigation of antimicrobial resistance

Antibiotic resistance had first been reported not long after the discovery of the first antibiotic and has remained a major public health issue ever since. Challenges are constantly encountered during the mitigation process of antibiotic resistance in the clinical setting; especially with the emergence of the formidable superbug, a bacteria with multiple resistance towards different antibiotics; this resulted in the term multidrug resistant (MDR) bacteria. This rapid evolution of the resistance phenomenon has propelled researchers to continuously uncover new antimicrobial agents in a bid to hopefully, downplay the rate of evolution despite a drying pipeline. Recently, there has been a paradigm shift in the mining of potential antimicrobials; in the past, targets for drug discovery were from microorganisms and at current, the focus has moved onto plants, this is mainly due to the beneficial attributes that plants are able to confer over that of microorganisms. This review will briefly discuss antibiotic resistance mechanisms employed by resistant bacteria followed by a detailed expository regarding the use of secondary metabolites from plants as a potential solution to the MDR pathogen. Finally, future prospects recommending enhancements to the usage of plant secondary metabolites to directly target antibiotic resistant pathogens will be discussed

Microbial Genomics: Innovative Targets and Mechanisms

Multidrug resistance (MDR) has become an increasing threat to global health because bacteria can develop resistance to antibiotics over time. Scientists worldwide are searching for new approaches that go beyond traditional antibiotic discovery and development pipelines. Advances in genomics, however, opened up an unexplored therapeutic opportunity for the discovery of new antibacterial agents. Genomic approaches have been used to discover several novel antibiotics that target critical processes for bacterial growth and survival, including histidine kinases (HKs), LpxC, FabI, peptide deformylase (PDF), and aminoacyl-tRNA synthetases (AaRS). In this review, we will discuss the use of microbial genomics in the search for innovative and promising drug targets as well as the mechanisms of action for novel antimicrobial agents. We will also discuss future directions on how the utilization of the microbial genomics approach could improve the odds of antibiotic development having a more successful outcome

Host–bacterial interactions:Outcomes of antimicrobial peptide applications

The bacterial membrane is part of a secretion system which plays an integral role to secrete proteins responsible for cell viability and pathogenicity; pathogenic bacteria, for example, secrete virulence factors and other membrane-associated proteins to invade the host cells through various types of secretion systems (Type I to Type IX). The bacterial membrane can also mediate microbial communities’ communication through quorum sensing (QS), by secreting auto-stimulants to coordinate gene expression. QS plays an important role in regulating various physiological processes, including bacterial biofilm formation while providing increased virulence, subsequently leading to antimicrobial resistance. Multi-drug resistant (MDR) bacteria have emerged as a threat to global health, and various strategies targeting QS and biofilm formation have been explored by researchers worldwide. Since the bacterial secretion systems play such a crucial role in host–bacterial interactions, this review intends to outline current understanding of bacterial membrane systems, which may provide new insights for designing approaches aimed at antimicrobials discovery. Various mechanisms pertaining interaction of the bacterial membrane with host cells and antimicrobial agents will be highlighted, as well as the evolution of bacterial membranes in evasion of antimicrobial agents. Finally, the use of antimicrobial peptides (AMPs) as a cellular device for bacterial secretion systems will be discussed as emerging potential candidates for the treatment of multidrug resistance infections

Mode of Action: Synergistic Interaction of Peppermint (Mentha x piperita L. Carl) Essential Oil and Meropenem Against Plasmid-Mediated Resistant E. coli

This study investigated the bactericidal mechanism of peppermint essential oil (PEO) when used singly and in combination with meropenem against multidrug resistant Escherichia coli. Chemical compositions of PEO were identified via GC-MS, followed by time-kill analysis which was performed to evaluate the antibacterial activities of PEO and meropenem. Furthermore, outer membrane permeability test, zeta potential measurement and scanning electron microscopy were performed to evaluate the ability of PEO in bacterial membrane disruption. Next, anti-quorum sensing assay was performed to assess the ability of PEO in quorum sensing inhibition. A complete killing activity was observed within five minutes of treatment with PEO and meropenem at sub-lethal concentrations. In addition, the outer membrane permeability test and zeta potential measurement performed indicated increase in the membrane permeability and membrane disruption which can be observed in the scanning electron micrograph. Furthermore, significant decrease in the light production of E. coli pSB1075 treated by PEO indicates the presence of quorum sensing inhibitors within PEO. The findings suggest that PEO has the ability to disrupt the bacterial outer membrane which increases membrane permeability, in addition to the possible inhibition of bacterial quorum sensing ability in multidrug resistant E. coli, aiding in the reversal of antibiotic resistance