Natural Products: Strategic Tools for Modulation of Biofilm Formation

ABSTRACT Many studies have evaluated the antimicrobial activity of natural products against various microorganisms, but to our knowledge there have been no studies of the possible use of natural products for their antimicrobial activity against Enterobacter hormaechei. In this study, we investigated vanillic acid (VA) for its antimicrobial activities and its modes of action against carbapenem-resistant E. hormaechei (CREH). The MIC of VA against CREH was determined by the agar diffusion method. The antibacterial action of VA against CREH was elucidated by measuring variations in intracellular ATP concentration, intracellular pH, membrane potential, and cell morphology. Moreover, the efficacy of VA against biofilm formation and VA damage to CREH cells embedded in biofilms were further explored. Our results show that VA was effective against CREH with a MIC of 0.8 mg/mL. VA could rupture the cell membrane integrity of CREH, as measured by a decrease of intracellular ATP, pH, and membrane potential, along with distinctive alternations in cell morphology. In addition, VA exerted a remarkable inhibitory effect on the biofilm formation of CREH and also killed CREH cells within biofilms. These findings show that VA has a potent antibacterial and antibiofilm activity against CREH and, hence, has the potential to be used clinically as a novel candidate agent to treat CREH infections and in the food industry as a food preservative and surface disinfectant. HIGHLIGHTS

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Searching Hit Potential Antimicrobials in Natural Compounds Space against Biofilm Formation

Molecules ◽

10.3390/molecules25225334 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5334

Author(s):

Roberto Pestana-Nobles ◽

Jorge A. Leyva-Rojas ◽

Juvenal Yosa

Keyword(s):

Natural Products ◽

Biofilm Formation ◽

Caulobacter Crescentus ◽

Resistant Bacteria ◽

Chronic Infections ◽

Aconitic Acid ◽

Starting Point ◽

In Silico Studies ◽

Biofilm Development

Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces and thus play a significant role in the persistence of bacterial infection and resistance to antimicrobial. About 65% and 80% of microbial and chronic infections are associated with biofilm formation, respectively. The increase in infections by multi-resistant bacteria instigates the need for the discovery of novel natural-based drugs that act as inhibitory molecules. The inhibition of diguanylate cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate (c-di-GMP), involved in the biofilm formation, represents a potential approach for preventing the biofilm development. It has been extensively studied using PleD protein as a model of DGC for in silico studies as virtual screening and as a model for in vitro studies in biofilms formation. This study aimed to search for natural products capable of inhibiting the Caulobacter crescentus enzyme PleD. For this purpose, 224,205 molecules from the natural products ZINC15 database, have been evaluated through molecular docking and molecular dynamic simulation. Our results suggest trans-Aconitic acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new inhibitors of the PleD protein and hence blocking the biofilm formation.

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Cyanobacterial Natural Products for the Inhibition of Biofilm Formation and Biofouling

CHIMIA International Journal for Chemistry ◽

10.2533/chimia.2007.373 ◽

2007 ◽

Vol 61 (6) ◽

pp. 373-377 ◽

Cited By ~ 21

Author(s):

Karl Gademann

Keyword(s):

Natural Products ◽

Biofilm Formation

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Effects of Natural Products on Bacterial Communication and Network-Quorum Sensing

BioMed Research International ◽

10.1155/2020/8638103 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Min Yang ◽

Fanying Meng ◽

Wen Gu ◽

Fengjiao Li ◽

Yating Tao ◽

...

Keyword(s):

Natural Products ◽

Quorum Sensing ◽

Virulence Factor ◽

Biofilm Formation ◽

Bacterial Flora ◽

External Environment ◽

Cell Communication ◽

Beneficial Bacteria ◽

Bacterial Communication ◽

Virulence Factor Production

Quorum sensing (QS) has emerged as a research hotspot in microbiology and medicine. QS is a regulatory cell communication system used by bacterial flora to signal to the external environment. QS influences bacterial growth, proliferation, biofilm formation, virulence factor production, antibiotic synthesis, and environmental adaptation. Through the QS system, natural products can regulate the growth of harmful bacteria and enhance the growth of beneficial bacteria, thereby improving human health. Herein, we review advances in the discovery of natural products that regulate bacterial QS systems.

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A Comparison of the Bioactivity of Usnic Acid versus Methylphloroacetophenone

Natural Product Communications ◽

10.1177/1934578x1801301224 ◽

2018 ◽

Vol 13 (12) ◽

pp. 1934578X1801301

Author(s):

Ratul Sarkar ◽

Navriti Mittal ◽

John Sorensen ◽

Tuhinadri Sen

Keyword(s):

Natural Products ◽

Antibiotic Resistance ◽

Natural Product ◽

Biofilm Formation ◽

Usnic Acid ◽

Lichen Species ◽

Rich Source ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Acid Versus

The identification of natural products that disrupt biofilm formation has become an area of recently expanded interest in combating antibiotic resistance. The formation of biofilms has been correlated with increased pathogenesis in many strains of Gram-negative bacteria. Molecules that disrupt the formation of biofilms therefore represent a potentially novel way to combat pathogenesis. Lichen natural products are an underexplored source of biofilm disrupting natural products. We have investigated the biofilm disrupting activity of the lichen natural product usnic acid (UA) in comparison to the biosynthetic precursor methylphloroacetophenone (MPA). We have observed in our assays that UA is more bioactive than MPA, suggesting a rationale for the biosynthesis of UA in a wide variety of lichen species. These results suggest that lichen natural products may prove to be a rich source of biofilm inhibitors.

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African Plant-Based Natural Products with Antivirulence Activities to the Rescue of Antibiotics

Antibiotics ◽

10.3390/antibiotics9110830 ◽

2020 ◽

Vol 9 (11) ◽

pp. 830

Author(s):

Christian Emmanuel Mahavy ◽

Pierre Duez ◽

Mondher ElJaziri ◽

Tsiry Rasamiravaka

Keyword(s):

Natural Products ◽

Biofilm Formation ◽

Pathogenic Bacteria ◽

Antimicrobial Agents ◽

Biological Activities ◽

Cell Communication ◽

Bacterial Virulence ◽

Resistant Bacteria ◽

Antibiotic Resistant ◽

African Plants

The worldwide emergence of antibiotic-resistant bacteria and the thread of widespread superbug infections have led researchers to constantly look for novel effective antimicrobial agents. Within the past two decades, there has been an increase in studies attempting to discover molecules with innovative properties against pathogenic bacteria, notably by disrupting mechanisms of bacterial virulence and/or biofilm formation which are both regulated by the cell-to-cell communication mechanism called ‘quorum sensing’ (QS). Certainly, targeting the virulence of bacteria and their capacity to form biofilms, without affecting their viability, may contribute to reduce their pathogenicity, allowing sufficient time for an immune response to infection and a reduction in the use of antibiotics. African plants, through their huge biodiversity, present a considerable reservoir of secondary metabolites with a very broad spectrum of biological activities, a potential source of natural products targeting such non-microbicidal mechanisms. The present paper aims to provide an overview on two main aspects: (i) succinct presentation of bacterial virulence and biofilm formation as well as their entanglement through QS mechanisms and (ii) detailed reports on African plant extracts and isolated compounds with antivirulence properties against particular pathogenic bacteria.

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Based Natural Products as Quorum Sensing Inhibitors in E. Coli: A Critical Review

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666211101155150 ◽

2021 ◽

Vol 21 ◽

Author(s):

A.P. Cardiliya ◽

A. Selvaraj ◽

M.J. Nanjan ◽

M.J.N. Chandrasekar

Keyword(s):

Natural Products ◽

Quorum Sensing ◽

Biofilm Formation ◽

Present Report ◽

Resistance Mechanism ◽

Multidrug Resistant ◽

Bacterial Diseases ◽

E Coli ◽

Pharmaceutical Industries ◽

Multidrug Resistant Pathogens

: The existence of multidrug–resistant (MDR) E .coli (superbugs) is a global health issue confronting humans, livestock, food processing units, and pharmaceutical industries. The quorum sensing (QS) controlling ability of the E .coli to form biofilms has become one of the important reasons for the emergence of multidrug-resistant pathogens. Quorum signaling activation and formation of biofilm lead to the emergence of antimicrobial resistance of the pathogens increasing the therapy difficulty for treating bacterial diseases. There is a crucial need, therefore, to reinforce newer therapeutic designs to overcome this resistance. As the infections caused by E .coli are attributed via the QS-regulated biofilm formation, easing this system by QS inhibitors is a possible strategy for treating bacterial diseases. Plant based natural products have been reported to bind to QS receptors and interrupt the QS systems of pathogens by inhibiting biofilm formation and disrupting the formed biofilms, thus minimizing the chances to develop a resistance mechanism. The present report reviews critically the QS capability of E .coli to form biofilms leading to multidrug resistant pathogens and the investigations that have been carried out so far on plant acquired natural products as QS inhibitors.

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Synergistic Antibiofilm Effect of Thymol and Piperine in Combination with Aminoglycosides Antibiotics against Four Salmonella enterica Serovars

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/1567017 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Christian Ramsès Tokam Kuaté ◽

Borel Bisso Ndezo ◽

Jean Paul Dzoyem

Keyword(s):

Natural Products ◽

Synergistic Effect ◽

Salmonella Enterica ◽

Biofilm Formation ◽

Antimicrobial Agents ◽

Inhibitory Concentration ◽

Assay Method ◽

Antibiofilm Activity ◽

Microtiter Plate Assay ◽

Broth Microdilution Method

Biofilms related to human infection have high levels of pathogenicity due to their resistance to antimicrobial agents. The discovery of antibiofilm agents is necessary. One approach to overcome this problem is the use of antibiotics agents’ combination. This study aimed to determine the efficacy of the combination of natural products thymol and piperine with three aminoglycosides antibiotics, amikacin, kanamycin, and streptomycin against biofilm-forming Salmonella enterica. The microtiter plate assay method was used to evaluate the biofilm-producing capacity of the isolates. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined by the broth microdilution method. The inhibition of biofilm formation and biofilm eradication was determined using the microtiter broth method. The checkerboard method was used to determine the combined effects of natural products with aminoglycosides antibiotics. All the tested isolates showed various levels of biofilm formation. Overall, combinations provided 43.3% of synergy in preventing the biofilm formation and 40% of synergy in eradicating preformed biofilms, and in both cases, no antagonism was observed. The combination of thymol with kanamycin showed a synergistic effect with 16- to 32-fold decrease of the minimum biofilm eradication concentration (MBEC) of kanamycin. The interaction of piperine with amikacin and streptomycin also revealed a synergistic effect with 16-fold reduction of the minimum biofilm inhibitory concentration (MBIC). The combination of thymol with the three antibiotics showed a strong synergistic effect in both inhibiting the biofilm formation and eradicating the preformed biofilm. This study demonstrates that thymol and piperine potentiate the antibiofilm activity of amikacin, kanamycin, and streptomycin. These combinations are a promising approach therapeutic to overcome the problem of Salmonella enterica biofilm-associated infections. In addition, these combinations could help reduce the concentration of individual components, thereby minimizing the nephrotoxicity of aminoglycosides antibiotics.

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