Developments in strategies for Quorum Sensing virulence factor inhibition to combat bacterial drug resistance

: Quorum sensing is defined as cell to cell communication between microorganisms, which enables microorganisms to behave as multicellular organisms. Quorum sensing enables many collaborative benefits such as synchronisation of virulence factors and biofilm formation. Both quorum sensing as well as biofilm formation encourage the development of drug resistance in microorganisms. Biofilm formation and quorum sensing are causally linked to each other and play role in the pathogenesis of microorganisms. With the increasing drug resistance against the available antibiotics and antifungal medications, scientists are combining different options to develop new strategies. Such strategies rely on the inhibition of the communication and virulence factors rather than on killing or inhibiting the growth of the microorganisms. This review encompasses the communication technique used by microorganisms, how microorganism resistance is linked to quorum sensing and various chemical strategies to combat quorum sensing and thereby drug resistance. Several compounds have been identified as quorum sensing inhibitors and are known to be effective in reducing resistance as they do not kill the pathogens but rather disrupt their communication. Natural compounds have been identified as anti-quorum sensing agents. However, natural compounds present several related disadvantages. Therefore, the need for the development of synthetic or semi-synthetic compounds has arisen. This review argues that anti-quorum sensing compounds are effective in disrupting quorum sensing and could therefore be effective in reducing microorganism drug resistance.

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Functionalized Chitosan Nanomaterials: A Jammer for Quorum Sensing

Polymers ◽

10.3390/polym13152533 ◽

2021 ◽

Vol 13 (15) ◽

pp. 2533

Author(s):

Moupriya Nag ◽

Dibyajit Lahiri ◽

Dipro Mukherjee ◽

Ritwik Banerjee ◽

Sayantani Garai ◽

...

Keyword(s):

Drug Resistance ◽

Quorum Sensing ◽

Targeted Delivery ◽

Direct Interaction ◽

Orthodontic Appliances ◽

Chronic Infections ◽

Functionalized Nanomaterials ◽

Low Toxicity ◽

Novel Target ◽

Positively Charged

The biggest challenge in the present-day healthcare scenario is the rapid emergence and spread of antimicrobial resistance due to the rampant use of antibiotics in daily therapeutics. Such drug resistance is associated with the enhancement of microbial virulence and the acquisition of the ability to evade the host’s immune response under the shelter of a biofilm. Quorum sensing (QS) is the mechanism by which the microbial colonies in a biofilm modulate and intercept communication without direct interaction. Hence, the eradication of biofilms through hindering this communication will lead to the successful management of drug resistance and may be a novel target for antimicrobial chemotherapy. Chitosan shows microbicidal activities by acting electrostatically with its positively charged amino groups, which interact with anionic moieties on microbial species, causing enhanced membrane permeability and eventual cell death. Therefore, nanoparticles (NPs) prepared with chitosan possess a positive surface charge and mucoadhesive properties that can adhere to microbial mucus membranes and release their drug load in a constant release manner. As the success in therapeutics depends on the targeted delivery of drugs, chitosan nanomaterial, which displays low toxicity, can be safely used for eradicating a biofilm through attenuating the quorum sensing (QS). Since the anti-biofilm potential of chitosan and its nano-derivatives are reported for various microorganisms, these can be used as attractive tools for combating chronic infections and for the preparation of functionalized nanomaterials for different medical devices, such as orthodontic appliances. This mini-review focuses on the mechanism of the downregulation of quorum sensing using functionalized chitosan nanomaterials and the future prospects of its applications.

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Anti-biofilm and Virulence Factor-Reducing Activities of Essential Oils and Oil Components as a Possible Option for Bacterial Infection Control

Planta Medica ◽

10.1055/a-1147-4671 ◽

2020 ◽

Vol 86 (08) ◽

pp. 520-537 ◽

Cited By ~ 2

Author(s):

Jürgen Reichling

Keyword(s):

Quorum Sensing ◽

Essential Oil ◽

Essential Oils ◽

Virulence Factor ◽

Model Organisms ◽

Regulation System ◽

Expression Of Genes ◽

Reporter Strains ◽

Violacein Production ◽

Essential Oil Compounds

AbstractPathogenic biofilm-associated bacteria that adhere to biological or nonbiological surfaces are a big challenge to the healthcare and food industries. Antibiotics or disinfectants often fail in an attempt to eliminate biofilms from those surfaces. Based on selected experimental research, this review deals with the potential biofilm-inhibiting, virulence factor-reducing, and biofilm-eradicating activities of essential oils and single essential oil compounds using Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Chromobacterium violaceum as model organisms. In addition, for the bacteria reviewed in this overview, different essential oils and essential oil compounds were reported to be able to modulate the expression of genes that are involved in the formation of autoinducer molecules, biofilms, and virulence factors. The anti-quorum sensing activity of some essential oils and single essential oil compounds was demonstrated using the gram-negative bacterium C. violaceum. Reporter strains of this bacterium produce the violet-colored compound violacein whose synthesis is regulated by quorum sensing autoinducer molecules called acylhomeserinlactones. Of great interest was the discovery that enantiomeric monoterpenes affected the quorum sensing regulation system in different ways. While the (+)-enantiomers of carvone, limonene, and borneol increased violacein formation, their (−)-analogues inhibited violacein production.For the successful eradication of biofilms and the bacteria living inside them, it is absolutely necessary that the lipophilic volatile substances can penetrate into the aqueous channels of biofilms. As shown in recent work, hydrophilic nano-delivery systems encapsulating essential oils/essential oil compounds with antibacterial effects may contribute to overcome this problem.

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Quorum Sensing: a Transcriptional Regulatory System Involved in the Pathogenicity of Burkholderia mallei

Infection and Immunity ◽

10.1128/iai.72.11.6589-6596.2004 ◽

2004 ◽

Vol 72 (11) ◽

pp. 6589-6596 ◽

Cited By ~ 57

Author(s):

Ricky L. Ulrich ◽

David DeShazer ◽

Harry B. Hines ◽

Jeffrey A. Jeddeloh

Keyword(s):

Quorum Sensing ◽

Virulence Factor ◽

Regulatory System ◽

In Silico Analysis ◽

Homoserine Lactone ◽

Burkholderia Mallei ◽

Wild Type ◽

Transcriptional Regulatory ◽

A Cell

ABSTRACT Numerous gram-negative bacterial pathogens regulate virulence factor expression by using a cell density mechanism termed quorum sensing (QS). An in silico analysis of the Burkholderia mallei ATCC 23344 genome revealed that it encodes at least two luxI and four luxR homologues. Using mass spectrometry, we showed that wild-type B. mallei produces the signaling molecules N-octanoyl-homoserine lactone and N-decanoyl-homoserine lactone. To determine if QS is involved in the virulence of B. mallei, we generated mutations in each putative luxIR homologue and tested the pathogenicities of the derivative strains in aerosol BALB/c mouse and intraperitoneal hamster models. Disruption of the B. mallei QS alleles, especially in RJ16 (bmaII) and RJ17 (bmaI3), which are luxI mutants, significantly reduced virulence, as indicated by the survival of mice who were aerosolized with 104 CFU (10 50% lethal doses [LD50s]). For the B. mallei transcriptional regulator mutants (luxR homologues), mutation of the bmaR5 allele resulted in the most pronounced decrease in virulence, with 100% of the challenged animals surviving a dose of 10 LD50s. Using a Syrian hamster intraperitoneal model of infection, we determined the LD50s for wild-type B. mallei and each QS mutant. An increase in the relative LD50 was found for RJ16 (bmaI1) (>967 CFU), RJ17 (bmaI3) (115 CFU), and RJ20 (bmaR5) (151 CFU) compared to wild-type B. mallei (<13 CFU). These findings demonstrate that B. mallei carries multiple luxIR homologues that either directly or indirectly regulate the biosynthesis of an essential virulence factor(s) that contributes to the pathogenicity of B. mallei in vivo.

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Effects of Antibiotics on Quorum Sensing in Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01230-07 ◽

2008 ◽

Vol 52 (10) ◽

pp. 3648-3663 ◽

Cited By ~ 212

Author(s):

Mette E. Skindersoe ◽

Morten Alhede ◽

Richard Phipps ◽

Liang Yang ◽

Peter O. Jensen ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Virulence Factor ◽

Dna Microarrays ◽

Underlying Mechanism ◽

Homoserine Lactone ◽

Reverse Transcription Pcr ◽

Animal Infection ◽

Beneficial Action ◽

Severe Infections

ABSTRACT During infection, Pseudomonas aeruginosa employs bacterial communication (quorum sensing [QS]) to coordinate the expression of tissue-damaging factors. QS-controlled gene expression plays a pivotal role in the virulence of P. aeruginosa, and QS-deficient mutants cause less severe infections in animal infection models. Treatment of cystic fibrosis (CF) patients chronically infected with P. aeruginosa with the macrolide antibiotic azithromycin (AZM) has been demonstrated to improve the clinical outcome. Several studies indicate that AZM may accomplish its beneficial action in CF patients by impeding QS, thereby reducing the pathogenicity of P. aeruginosa. This led us to investigate whether QS inhibition is a common feature of antibiotics. We present the results of a screening of 12 antibiotics for their QS-inhibitory activities using a previously described QS inhibitor selector 1 strain. Three of the antibiotics tested, AZM, ceftazidime (CFT), and ciprofloxacin (CPR), were very active in the assay and were further examined for their effects on QS-regulated virulence factor production in P. aeruginosa. The effects of the three antibiotics administered at subinhibitory concentrations were investigated by use of DNA microarrays. Consistent results from the virulence factor assays, reverse transcription-PCR, and the DNA microarrays support the finding that AZM, CFT, and CPR decrease the expression of a range of QS-regulated virulence factors. The data suggest that the underlying mechanism may be mediated by changes in membrane permeability, thereby influencing the flux of N-3-oxo-dodecanoyl-l-homoserine lactone.

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Chemical composition and modulation of bacterial drug resistance of the essential oil from leaves of Croton grewioides

Microbial Pathogenesis ◽

10.1016/j.micpath.2017.09.034 ◽

2017 ◽

Vol 111 ◽

pp. 468-471 ◽

Cited By ~ 5

Author(s):

Vivianne Marcelino de Medeiros ◽

Yuri Mangueira do Nascimento ◽

Augusto Lopes Souto ◽

Sara Alves Lucena Madeiro ◽

Vicente Carlos de Oliveira Costa ◽

...

Keyword(s):

Drug Resistance ◽

Chemical Composition ◽

Essential Oil ◽

Bacterial Drug Resistance

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The Mucoid Switch in Pseudomonas aeruginosa Represses Quorum Sensing Systems and Leads to Complex Changes to Stationary Phase Virulence Factor Regulation

PLoS ONE ◽

10.1371/journal.pone.0096166 ◽

2014 ◽

Vol 9 (5) ◽

pp. e96166 ◽

Cited By ~ 24

Author(s):

Ben Ryall ◽

Marta Carrara ◽

James E. A. Zlosnik ◽

Volker Behrends ◽

Xiaoyun Lee ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Stationary Phase ◽

Virulence Factor ◽

Sensing Systems

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Research on intervention methods of nosocomial infection in neurosurgery

Reports in Clinical Studies and Medicine ◽

10.18282/rcsm.v2.i1.782 ◽

2020 ◽

Vol 2 (1) ◽

pp. 5

Author(s):

Sung-Won Kim

Keyword(s):

Risk Factors ◽

Drug Resistance ◽

Infection Rate ◽

Effective Means ◽

Severe Trauma ◽

High Infection Rate ◽

Intervention Measures ◽

Bacterial Drug Resistance ◽

High Infection

<p>The proportion of critically ill patients from neurosurgery wards in hospitals is significantly higher than that from other departments. These patients suffer from low immune. At the same time, because of the severe trauma after surgery and the complexity of pathogens in patients, antibiotics are frequently used. However, the of bacterial drug resistance is relatively high because of the particularity of hospitals, which is a major reason for the high infection rate of neurosurgery patients. Therefore, regarding to these risk factors, intervention measures should be actively explored in hospitals, so as to control the infection rate, reduce the possibility of infection in neurosurgery patients, improve the rehabilitation efficiency of patients, and reduce unnecessary suffering of patients caused by infection. This is also an effective means to improve the quality of hospital medical care. </p>

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Overview of ß-lactamase incidence on bacterial drug resistance

African Journal of Food Agriculture Nutrition and Development ◽

10.4314/ajfand.v4i13.71835 ◽

2011 ◽

Vol 4 (13) ◽

Author(s):

B Zeba

Keyword(s):

Drug Resistance ◽

Bacterial Drug Resistance

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Malleilactone Is a Burkholderia pseudomallei Virulence Factor Regulated by Antibiotics and Quorum Sensing

Journal of Bacteriology ◽

10.1128/jb.00008-18 ◽

2018 ◽

Vol 200 (14) ◽

Cited By ~ 19

Author(s):

Jennifer R. Klaus ◽

Jacqueline Deay ◽

Benjamin Neuenswander ◽

Wyatt Hursh ◽

Zhe Gao ◽

...

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Quorum Sensing ◽

Virulence Factor ◽

Mammalian Cells ◽

Burkholderia Pseudomallei ◽

Gene Clusters ◽

Close Relative ◽

Burkholderia Thailandensis ◽

Content Type

ABSTRACT Burkholderia pseudomallei , the causative agent of melioidosis, encodes almost a dozen predicted polyketide (PK) biosynthetic gene clusters. Many of these are regulated by LuxR-I-type acyl-homoserine (AHL) quorum-sensing systems. One of the PK gene clusters, the mal gene cluster, is conserved in the close relative Burkholderia thailandensis . The B. thailandensis mal genes code for the cytotoxin malleilactone and are regulated by a genetically linked LuxR-type transcription factor, MalR. Although AHLs typically interact with LuxR-type proteins to modulate gene transcription, the B. thailandensis MalR does not appear to be an AHL receptor. Here, we characterize the mal genes and MalR in B. pseudomallei . We use chemical analyses to demonstrate that the B. pseudomallei mal genes code for malleilactone. Our results show that MalR and the mal genes contribute to the ability of B. pseudomallei to kill Caenorhabditis elegans . In B. thailandensis , antibiotics like trimethoprim can activate MalR by driving transcription of the mal genes, and we demonstrate that some of the same antibiotics induce expression of B. pseudomallei malR . We also demonstrate that B. pseudomallei MalR does not respond directly to AHLs. Our results suggest that MalR is indirectly repressed by AHLs, possibly through a repressor, ScmR. We further show that malleilactone is a B. pseudomallei virulence factor and provide the foundation for understanding how malleilactone contributes to the pathology of melioidosis infections. IMPORTANCE Many bacterially produced polyketides are cytotoxic to mammalian cells and are potentially important contributors to pathogenesis during infection. We are interested in the polyketide gene clusters present in Burkholderia pseudomallei , which causes the often-fatal human disease melioidosis. Using knowledge gained by studies in the close relative Burkholderia thailandensis , we show that one of the B. pseudomallei polyketide biosynthetic clusters produces a cytotoxic polyketide, malleilactone. Malleilactone contributes to B. pseudomallei virulence in a Caenorhabditis elegans infection model and is regulated by an orphan LuxR family quorum-sensing transcription factor, MalR. Our studies demonstrate that malleilactone biosynthesis or MalR could be new targets for developing therapeutics to treat melioidosis.

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