Antibacterial activity of oleanolic and ursolic acids and their derivatives

AbstractBacterial resistance to antibiotics is increasing at an alarming rate and many commonly used antibiotics are no longer effective. Thus, there is considerable interest in investigating novel antibacterial compounds, such as the plant-derived pentacyclic triterpenoids, including oleanolic acid (OA), ursolic acid (UA) and their derivatives. These compounds can be isolated from many medicinal and crop plants and their antibacterial, antiviral, antiulcer and anti-inflammatory effects are well documented. OA and UA are active against many bacterial species, particularly Gram-positive species, including mycobacteria. They inhibit bacterial growth and survival, and the spectrum of minimal inhibitory concentration (MIC) values is very broad. In addition, OA, UA and their derivatives display potent antimutagenic activity. Studies to identify the cellular targets and molecular mechanisms of OA and UA action were initiated a few years ago and it has already been demonstrated that both acids influence bacterial gene expression, the formation and maintenance of biofilms, cell autolysis and peptidoglycan turnover. Before these compounds can be used clinically as antimicrobial agents, further extensive studies are required to determine their cytotoxicity and the optimum mode of their application.

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Quorum Sensing Regulation as a Target for Antimicrobial Therapy

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666211202115259 ◽

2021 ◽

Vol 21 ◽

Author(s):

Caterine Henríquez Ruiz ◽

Estefanie Osorio-Llanes ◽

Mayra Hernández Trespalacios ◽

Evelyn Mendoza-Torres ◽

Wendy Rosales ◽

...

Keyword(s):

Quorum Sensing ◽

Molecular Mechanisms ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Bacterial Species ◽

Cell Communication ◽

Structural Evolution ◽

Structural Diversity ◽

Signal Molecules ◽

Bacterial Survival

: Some bacterial species use a cell-to-cell communication mechanism called Quorum Sensing (QS). Bacteria release small diffusible molecules, usually termed signals which allow the activation of beneficial phenotypes that guarantee bacterial survival and the expression of a diversity of virulence genes in response to an increase in population density. The study of the molecular mechanisms that relate signal molecules with bacterial pathogenesis is an area of growing interest due to its use as a possible therapeutic alternative through the development of synthetic analogues of autoinducers as a strategy to regulate bacterial communication as well as the study of bacterial resistance phenomena, the study of these relationships is based on the structural diversity of natural or synthetic autoinducers and their ability to inhibit bacterial QS, which can be approached with a molecular perspective from the following topics: i) Molecular signals and their role in QS regulation; ii) Strategies in the modulation of Quorum Sensing; iii) Analysis of Bacterial QS circuit regulation strategies; iv) Structural evolution of natural and synthetic autoinducers as QS regulators. This mini-review allows a molecular view of the QS systems, showing a perspective on the importance of the molecular diversity of autoinducer analogs as a strategy for the design of new antimicrobial agents.

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Bacterial Resistance to Antisense Peptide Phosphorodiamidate Morpholino Oligomers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00850-12 ◽

2012 ◽

Vol 56 (12) ◽

pp. 6147-6153 ◽

Cited By ~ 24

Author(s):

Susan E. Puckett ◽

Kaleb A. Reese ◽

Georgi M. Mitev ◽

Valerie Mullen ◽

Rudd C. Johnson ◽

...

Keyword(s):

Bacterial Resistance ◽

Acyl Carrier Protein ◽

Essential Gene ◽

Resistant Mutant ◽

Resistant Isolate ◽

Carrier Protein ◽

Bacterial Gene ◽

Content Type ◽

Bacterial Gene Expression ◽

Phosphorodiamidate Morpholino Oligomers

ABSTRACTPeptide phosphorodiamidate morpholino oligomers (PPMOs) are synthetic DNA mimics that bind cRNA and inhibit bacterial gene expression. The PPMO (RFF)3RXB-AcpP (where R is arginine, F, phenylalanine, X is 6-aminohexanoic acid, B is β-alanine, and AcpP is acyl carrier protein) is complementary to 11 bases of the essential geneacpP(which encodes acyl carrier protein). The MIC of (RFF)3RXB-AcpP was 2.5 μM (14 μg/ml) inEscherichia coliW3110. The rate of spontaneous resistance ofE. colito (RFF)3RXB-AcpP was 4 × 10−7mutations/cell division. A spontaneous (RFF)3RXB-AcpP-resistant mutant (PR200.1) was isolated. The MIC of (RFF)3RXB-AcpP was 40 μM (224 μg/ml) for PR200.1. The MICs of standard antibiotics for PR200.1 and W3110 were identical. The sequence ofacpPwas identical in PR200.1 and W3110. PR200.1 was also resistant to other PPMOs conjugated to (RFF)3RXB or peptides with a similar composition or pattern of cationic and nonpolar residues. Genomic sequencing of PR200.1 identified a mutation insbmA, which encodes an active transport protein. In separate experiments, a (RFF)3RXB-AcpP-resistant isolate (RR3) was selected from a transposome library, and the insertion was mapped tosbmA. Genetic complementation of PR200.1 or RR3 withsbmArestored susceptibility to (RFF)3RXB-AcpP. Deletion ofsbmAcaused resistance to (RFF)3RXB-AcpP. We conclude that resistance to (RFF)3RXB-AcpP was linked to the peptide and not the phosphorodiamidate morpholino oligomer, dependent on the composition or repeating pattern of amino acids, and caused by mutations insbmA. The data further suggest that (RFF)3R-XB PPMOs may be transported across the plasma membrane by SbmA.

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Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues

Molecules ◽

10.3390/molecules26185608 ◽

2021 ◽

Vol 26 (18) ◽

pp. 5608

Author(s):

Jilan A. Nazeam ◽

Ghada M. Ragab ◽

Amira A. El-Gazar ◽

Shereen S. El-Mancy ◽

Lina Jamil ◽

...

Keyword(s):

Molecular Mechanisms ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Acne Vulgaris ◽

In Vivo Model ◽

Biofilm Inhibition ◽

Behavioral Alteration ◽

Antibiotic Development ◽

Ppar Γ

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.

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Understanding membrane-active antimicrobial peptides

Quarterly Reviews of Biophysics ◽

10.1017/s0033583517000087 ◽

2017 ◽

Vol 50 ◽

Cited By ~ 26

Author(s):

Huey W. Huang ◽

Nicholas E. Charron

Keyword(s):

Antimicrobial Peptides ◽

Soft Matter ◽

Structural Changes ◽

Molecular Mechanisms ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Molecular Structures ◽

Membrane Domain ◽

Defense Proteins ◽

Bacterial Membranes

AbstractBacterial membranes represent an attractive target for the design of new antibiotics to combat widespread bacterial resistance to traditional inhibitor-based antibiotics. Understanding how antimicrobial peptides (AMPs) and other membrane-active agents attack membranes could facilitate the design of new, effective antimicrobials. AMPs, which are small, gene-encoded host defense proteins, offer a promising basis for the study of membrane-active antimicrobial agents. These peptides are cationic and amphipathic, spontaneously binding to bacterial membranes and inducing transmembrane permeability to small molecules. Yet there are often confusions surrounding the details of the molecular mechanisms of AMPs. Following the doctrine of structure–function relationship, AMPs are often viewed as the molecular scaffolding of pores in membranes. Instead we believe that the full mechanism of AMPs is understandable if we consider the interactions of AMPs with the whole membrane domain, where interactions induce structural transformations of the entire membrane, rather than forming localized molecular structures. We believe that it is necessary to consider the entire soft matter peptide-membrane system as it evolves through several distinct states. Accordingly, we have developed experimental techniques to investigate the state and structure of the membrane as a function of the bound peptide to lipid ratio, exactly as AMPs in solution progressively bind to the membrane and induce structural changes to the entire system. The results from these studies suggest that global interactions of AMPs with the membrane domain are of fundamental importance to understanding the antimicrobial mechanisms of AMPs.

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Molecular Mechanisms of Bacterial Resistance to Metal and Metal Oxide Nanoparticles

International Journal of Molecular Sciences ◽

10.3390/ijms20112808 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2808 ◽

Cited By ~ 27

Author(s):

Nereyda Niño-Martínez ◽

Marco Felipe Salas Orozco ◽

Gabriel-Alejandro Martínez-Castañón ◽

Fernando Torres Méndez ◽

Facundo Ruiz

Keyword(s):

Metal Oxide ◽

Molecular Mechanisms ◽

Bacterial Resistance ◽

Bacterial Species ◽

Metal Oxide Nanoparticles ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Resistant Bacteria ◽

Oxide Nanoparticles ◽

Multidrug Resistant Bacteria

The increase in bacterial resistance to one or several antibiotics has become a global health problem. Recently, nanomaterials have become a tool against multidrug-resistant bacteria. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. Several in vitro studies report that metal nanoparticles have antimicrobial properties against a broad spectrum of bacterial species. However, until recently, the bacterial resistance mechanisms to the bactericidal action of the nanoparticles had not been investigated. Some of the recently reported resistance mechanisms include electrostatic repulsion, ion efflux pumps, expression of extracellular matrices, and the adaptation of biofilms and mutations. The objective of this review is to summarize the recent findings regarding the mechanisms used by bacteria to counteract the antimicrobial effects of nanoparticles.

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Mechanisms of antimicrobial resistance development in bacteria

Theoretical and Applied Veterinary Medicine ◽

10.32819/2020.83033 ◽

2020 ◽

Vol 8 (3) ◽

pp. 226-236

Author(s):

T. I. Stetsko ◽

V. P. Muzyka ◽

M. R. Kozak

Keyword(s):

Antimicrobial Resistance ◽

Antimicrobial Agent ◽

Resistance Genes ◽

Target Genes ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Bacterial Species ◽

Animal Health ◽

Significant Risk ◽

Animal Origin

Antimicrobial resistance poses a significant risk to animal health by reducing the effectiveness of the treatment and prevention of many infections caused by bacteria. Antibiotic resistance threatens human health by transmitting resistant strains of microorganisms or resistance genes from animals to humans through the food chain. Life-threatening infections that were previously manageable can become incurable through antimicrobial resistance. Antimicrobial resistance can be divided into two main types: natural and acquired. Natural bacterial resistance is associated with the absence or inaccessibility of target cites for the action of certain antimicrobial agents. The acquired resistance is specific and associated with the acquisition of extraneous resistance genes or mutational modification of chromosomal target genes. The resistance of bacteria to antimicrobial drugs varies depending on the antimicrobial agent, species or genus of bacteria, and the mechanism of resistance. Resistance to the same antimicrobial agent can be mediated by different resistance mechanisms. In some cases, the same resistance gene or mechanism are related to a wide variety of bacteria, whereas in other cases, resistance genes or mechanisms are restricted to certain bacterial species or genera. Bacterial resistance to different classes of antibiotics with common mechanisms often leads to the multidrug resistance. The data presented in this review focuses exclusively on the resistance genes and mechanisms found in bacteria of animal origin and on antimicrobials used in the veterinary medicine. For better coverage of the topic, information on the mechanisms of resistance is presented separately for each class of antimicrobial agents.

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Current Mechanism of Bacterial Resistance to Antimicrobials

SAMRIDDHI A Journal of Physical Sciences Engineering and Technology ◽

10.18090/samriddhi.v10i01.8 ◽

2018 ◽

Vol 10 (01) ◽

pp. 55-64

Author(s):

Sonali Gangwar ◽

Keerti Kaushik ◽

Maya Datt Joshi

Keyword(s):

Molecular Mechanisms ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Hospital Environment ◽

Health Concern ◽

Resistant Bacteria ◽

Drug Resistant ◽

Pathogenic Variants ◽

Drug Resistant Bacteria

Serious infectious diseases are caused by bacterial pathogens that represents a serious public health concern. Antimicrobial agents are indicated for the treatment bacterial infections.Various bacteria carries several resistance genes also called multidrug resistant (MDR). Multidrug resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting the reservoirs of antibiotic resistant bacteria are present outside the hospital. Drug resistant bacteria that are selected with a single drug are also frequently multi-drug resistant against multiple structurally different drugs, thus confounding the chemotherapeutic efficacy of infectious disease caused by such pathogenic variants. The molecular mechanisms by which bacteria have common resistance to antibiotics are diverse and complex. This review highlights the mechanism of bacterial resistance to antimicrobials.

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Molecular Mechanisms оf Persistence оf Bacteria

Journal of microbiology epidemiology immunobiology ◽

10.36233/0372-9311-2020-97-3-10 ◽

2020 ◽

Vol 97 (3) ◽

pp. 271-279

Author(s):

Boris G. Andryukov ◽

Irina N. Lyapun

Keyword(s):

Pathogenic Bacteria ◽

Molecular Mechanisms ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Molecular Genetic ◽

Rapid Evolution ◽

Cell Subpopulation ◽

Bacterial Persistence ◽

Persister Cells ◽

Phenotypic Resistance

A significant mortality rate from infectious diseases is largely mediated by the widespread and uncontrolled use of antibiotics, which has led to the emergence of drug-resistant strains of bacteria. The rapid evolution of bacterial resistance to antimicrobials is a serious challenge for modern health care, mediates the need to create new antibiotic agents, as well as to intensify the study of molecular mechanisms underlying the formation of microorganism resistance. One of these mechanisms is bacterial persistence, manifested by the formation of persistent cells in the culture, which are a phenotypic variant of the isogenic population. The persistence of bacteria can occur spontaneously, regardless of exposure to antimicrobials or environmental reasons, such as lack of nutrients, oxidative stress or hypoxia. This small cell subpopulation is able to maintain viability even in the presence of antimicrobial agents at concentrations many times higher than therapeutic. The presence of persistent cells of pathogenic bacteria in the host organism reduces the effectiveness of antibiotic treatment, not due to the genotypic drug resistance of the microorganism, but due to the presence of phenotypic resistance of persister cells. The difference is fundamental, since cell-persisters are insensitive to any antibiotics and the development of fundamentally new antimicrobial strategies is necessary for their eradication. Persister cells are phenotypic variants of the maternal culture of bacteria that are present in all populations of microorganisms, and after the onset of favorable conditions, they are able to reclaim and form a new generation of vegetative bacteria. This review discusses modern concepts of the molecular genetic mechanisms of bacterial persistence with an emphasis on their clinical significance for the occurrence of persistent infections, and discusses innovative technologies for the eradication of resistant cell forms of microorganisms.

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Comparative Review of the Responses of Listeria monocytogenes and Escherichia coli to Low pH Stress

Genes ◽

10.3390/genes11111330 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1330

Author(s):

Talia Arcari ◽

Marie-Lucie Feger ◽

Duarte N. Guerreiro ◽

Jialun Wu ◽

Conor P. O’Byrne

Keyword(s):

Escherichia Coli ◽

Listeria Monocytogenes ◽

Pathogenic Bacteria ◽

Molecular Mechanisms ◽

Bacterial Species ◽

Acid Stress ◽

Low Ph ◽

Growth And Survival ◽

Ph Stress ◽

Comparative Review

Acidity is one of the principal physicochemical factors that influence the behavior of microorganisms in any environment, and their response to it often determines their ability to grow and survive. Preventing the growth and survival of pathogenic bacteria or, conversely, promoting the growth of bacteria that are useful (in biotechnology and food production, for example), might be improved considerably by a deeper understanding of the protective responses that these microorganisms deploy in the face of acid stress. In this review, we survey the molecular mechanisms used by two unrelated bacterial species in their response to low pH stress. We chose to focus on two well-studied bacteria, Escherichia coli (phylum Proteobacteria) and Listeria monocytogenes (phylum Firmicutes), that have both evolved to be able to survive in the mammalian gastrointestinal tract. We review the mechanisms that these species use to maintain a functional intracellular pH as well as the protective mechanisms that they deploy to prevent acid damage to macromolecules in the cells. We discuss the mechanisms used to sense acid in the environment and the regulatory processes that are activated when acid is encountered. We also highlight the specific challenges presented by organic acids. Common themes emerge from this comparison as well as unique strategies that each species uses to cope with acid stress. We highlight some of the important research questions that still need to be addressed in this fascinating field.

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