Does quorum sensing interference affect the fitness of bacterial pathogens in the real world?

Liu, Yiying; Qin, Qi; Defoirdt, Tom

doi:10.1111/1462-2920.14446

Cited by 17 publications

(9 citation statements)

References 80 publications

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“…Intercellular communication might be mediated by exosome vesicles or via the sharing of signaling molecules, as recently demonstrated for many unicellular organisms. Several examples of quorum sensing among bacterial pathogens have been described, resulting in differential responses during interactions with the environment and the host during invasion or differences in persistence capacity within a complex microbial community [73]. Trypanosoma brucei lacks G protein receptor signaling.…”

Section: Discussionmentioning

confidence: 99%

Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication

et al. 2021

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Background Pentavalent antimonial-based chemotherapy is the first-line approach for leishmaniasis treatment and disease control. Nevertheless antimony-resistant parasites have been reported in some endemic regions. Treatment refractoriness is complex and is associated with patient- and parasite-related variables. Although amastigotes are the parasite stage in the vertebrate host and, thus, exposed to the drug, the stress caused by trivalent antimony in promastigotes has been shown to promote significant modification in expression of several genes involved in various biological processes, which will ultimately affect parasite behavior. Leishmania (Viannia) guyanensis is one of the main etiological agents in the Amazon Basin region, with a high relapse rate (approximately 25%). Methods Herein, we conducted several in vitro analyses with L. (V.) guyanensis strains derived from cured and refractory patients after treatment with standardized antimonial therapeutic schemes, in addition to a drug-resistant in vitro-selected strain. Drug sensitivity assessed through Sb(III) half-maximal inhibitory concentration (IC50) assays, growth patterns (with and without drug pressure) and metacyclic-like percentages were determined for all strains and compared to treatment outcomes. Finally, co-cultivation without intercellular contact was followed by parasitic density and Sb(III) IC50 measurements. Results Poor treatment response was correlated with increased Sb(III) IC50 values. The decrease in drug sensitivity was associated with a reduced cell replication rate, increased in vitro growth ability, and higher metacyclic-like proportion. Additionally, in vitro co-cultivation assays demonstrated that intercellular communication enabled lower drug sensitivity and enhanced in vitro growth ability, regardless of direct cell contact. Conclusions Data concerning drug sensitivity in the Viannia subgenus are emerging, and L. (V.) guyanensis plays a pivotal epidemiological role in Latin America. Therefore, investigating the parasitic features potentially related to relapses is urgent. Altogether, the data presented here indicate that all tested strains of L. (V.) guyanensis displayed an association between treatment outcome and in vitro parameters, especially the drug sensitivity. Remarkably, sharing enhanced growth ability and decreased drug sensitivity, without intercellular communication, were demonstrated. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication

et al. 2021

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“…In order to develop truly solid QS inhibitor therapeutic alternatives to combat this remarkable pathogen, a much better understanding of its virulence and actions during infections is necessary. Even though the laboratory results are promising, it is undeniable that there is the need of thorough understanding of the knowledge of the impact of QS inhibition on the pathogen fitness in more convincing circumstances, such as interactions with a host, the external environment, and complex microbial communities (Liu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosa

et al. 2020

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Pseudomonas aeruginosa is among the top three gram-negative bacteria according to the WHO's critical priority list of pathogens against which newer antibiotics are urgently needed and considered a global threat due to multiple drug resistance. This situation demands unconventional antimicrobial strategies such as the inhibition of quorum sensing to alleviate the manifestation of classical resistance mechanisms. Here, we report that 2,4-di-tert-butylphenol (2,4-DBP), isolated from an endophytic fungus, Daldinia eschscholtzii, inhibits the quorum-sensing properties of P. aeruginosa. We have found that treating P. aeruginosa with 2,4-DBP substantially reduced the secretion of virulence factors as well as biofilm, and its associated factors that are controlled by quorum sensing, in a dose-dependent manner. Concomitantly, 2,4-DBP also significantly reduced the expression of quorum sensing-related genes, i.e., lasI, lasR, rhlI, and rhlR significantly. Importantly, 2,4-DBP restricted the adhesion and invasion of P. aeruginosa to the A549 lung alveolar carcinoma cells. In addition, bactericidal assay with 2,4-DBP exhibited synergism with ampicillin to kill P. aeruginosa. Furthermore, our computational studies predicted that 2,4-DBP could bind to the P. aeruginosa quorumsensing receptors LasR and RhlR. Collectively, these data suggest that 2,4-DBP can be exploited as a standalone drug or in combination with antibiotic(s) as an anti-virulence and anti-biofilm agent to combat the multidrug resistant P. aeruginosa infection.

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“…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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Does quorum sensing interference affect the fitness of bacterial pathogens in the real world?

Cited by 17 publications

References 80 publications

Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication

Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication

2,4-Di-Tert-Butylphenol Isolated From an Endophytic Fungus, Daldinia eschscholtzii, Reduces Virulence and Quorum Sensing in Pseudomonas aeruginosa

Challenges and Limitations of Anti-quorum Sensing Therapies

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