In Silico Evaluation of the Impacts of Quorum Sensing Inhibition (QSI) on Strain Competition and Development of QSI Resistance

Wei, Guopeng; Walsh, Connor; Hiller, N. Luisa; Mărculescu, Radu

doi:10.1038/srep35136

Cited by 14 publications

(12 citation statements)

References 66 publications

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“…One treatment used is to modify the microenvironmental conditions during QSI protocol therapy to combat the resistance phenomenon. A supplementary investigation brought up valuable information through an in silico study of QSI-based therapies, focused on EPS, showing that bacterial spread decreases and demonstrating that it is a good option to continue within new research phases [ 97 ].…”

Section: Resistance To Qsismentioning

confidence: 99%

Mechanisms of Inhibition of Quorum Sensing as an Alternative for the Control of E. coli and Salmonella

2022

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Quorum sensing (QS) is a process of cell–cell communication for bacteria such as E. coli and Salmonella that cause foodborne diseases, with the production, release, and detection of autoinducer (AI) molecules that participate in the regulation of virulence genes. All of these proteins are useful in coordinating collective behavior, the expression of virulence factors, and the pathogenicity of Gram-negative bacteria. In this work, we review the natural or synthetic inhibitor molecules of QS that inactivate the autoinducer and block QS regulatory proteins in E. coli and Salmonella. Furthermore, we describe mechanisms of QS inhibitors (QSIs) that act as competitive inhibitors, being a useful tool for preventing virulence gene expression through the downregulation of AI-2 production pathways and the disruption of signal uptake. In addition, we showed that QSIs have negative regulatory activity of genes related to bacterial biofilm formation on clinical artifacts, which confirms the therapeutic potential of QSIs in the control of infectious pathogens. Finally, we discuss resistance to QSIs, the design of next-generation QSIs, and how these molecules can be leveraged to provide a new antivirulence therapy to combat diseases caused by E. coli or Salmonella.

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Section: Resistance To Qsismentioning

confidence: 99%

Mechanisms of Inhibition of Quorum Sensing as an Alternative for the Control of E. coli and Salmonella

2022

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“…Thus, contrary to the prevailing opinion, there is a possibility of developing resistance to QQ therapies (Figure 1). In silico modeling seems to be one of the potential solutions limiting the spread of resistance to QQ therapies (Wei et al, 2016). The topic of resistance against QQ therapies was discussed in details in review papers by Defoirdt et al (2010), García-Contreras et al (2013a), Kalia et al (2014), and Liu et al (2018b).…”

Section: The Third Objection – the Lack Of Possibility To Develop Resmentioning

confidence: 99%

Challenges and Limitations of Anti-quorum Sensing Therapies

Krzyżek

2019

Front. Microbiol.

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Quorum sensing (QS) is a mechanism allowing microorganisms to sense population density and synchronously control genes expression. It has been shown that QS supervises the activity of many processes important for microbial pathogenicity, e.g., sporulation, biofilm formation, and secretion of enzymes or membrane vesicles. This contributed to the concept of anti-QS therapy [also called quorum quenching (QQ)] and the opportunity of its application in fighting against various types of pathogens. In recent years, many published articles reported promising results indicating the possibility of reducing pathogenicity of tested microorganisms and their easier eradication when co-treated with antibiotics. The aim of the present article is to point to the opposite, negative side of the QQ therapy, with particular emphasis on three fundamental properties attributed to anti-QS substances: the selectivity, virulence reduction, and lack of resistance against QQ. This point of view may highlight new directions of research, which should be taken into account in the future before the widespread introduction of QQ therapies in the treatment of people.

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“…Mitri et al ( 2011 ) found that addition of new species in a multispecies biofilm especially in resource limited scenarios would reduce the fitness of existing cooperative cells that secrete public goods. In addition, the ecological advantages of quorum sensing (QS) -regulated enzyme production (Schluter et al, 2016 ), QS inhibition (Wei et al, 2016 ) and evolution of bacteriocin production (Bucci et al, 2011 ) in biofilms have also been investigated using IbM.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Polymeric Substance Production and Aggregated Bacteria Colonization Influence the Competition of Microbes in Biofilms

et al. 2017

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The production of extracellular polymeric substance (EPS) is important for the survival of biofilms. However, EPS production is costly for bacteria and the bacterial strains that produce EPS (EPS+) grow in the same environment as non-producers (EPS−) leading to competition between these strains for nutrients and space. The outcome of this competition is likely to be dependent on factors such as initial attachment, EPS production rate, ambient nutrient levels and quorum sensing. We use an Individual-based Model (IbM) to study the competition between EPS+ and EPS− strains by varying the nature of initial colonizers which can either be in the form of single cells or multicellular aggregates. The microbes with EPS+ characteristics obtain a competitive advantage if they initially colonize the surface as smaller aggregates and are widely spread-out between the cells of EPS−, when both are deposited on the substratum. Furthermore, the results show that quorum sensing-regulated EPS production may significantly reduce the fitness of EPS producers when they initially deposit as aggregates. The results provide insights into how the distribution of bacterial aggregates during initial colonization could be a deciding factor in the competition among different strains in biofilms.

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In Silico Evaluation of the Impacts of Quorum Sensing Inhibition (QSI) on Strain Competition and Development of QSI Resistance

Cited by 14 publications

References 66 publications

Mechanisms of Inhibition of Quorum Sensing as an Alternative for the Control of E. coli and Salmonella

Mechanisms of Inhibition of Quorum Sensing as an Alternative for the Control of E. coli and Salmonella

Challenges and Limitations of Anti-quorum Sensing Therapies

Extracellular Polymeric Substance Production and Aggregated Bacteria Colonization Influence the Competition of Microbes in Biofilms

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