Microbial quorum sensing: a tool or a target for antimicrobial therapy?

Raina, Sheetal; Vizio, Daniela De; Odell, Mark; Clements, Mark O.; Vanhulle, Sophie; Keshavarz, Tajalli

doi:10.1042/ba20090072

Cited by 81 publications

(48 citation statements)

References 220 publications

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“…In laboratory growth conditions, these two arms of the P. aeruginosa AHL QS system are intimately connected and regulate one another (14,17). Strains defective in Las or Rhl signaling show reduced virulence, and considerable research has been concentrated on developing antimicrobials that interfere with these systems (18)(19)(20)(21)(22)(23).…”

mentioning

confidence: 99%

Quorum Sensing Is Accompanied by Global Metabolic Changes in the Opportunistic Human Pathogen Pseudomonas aeruginosa

2015

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Pseudomonas aeruginosa uses N-acyl-homoserine lactone (AHL)-dependent quorum sensing (QS) systems to control the expression of secreted effectors. These effectors can be crucial to the ecological fitness of the bacterium, playing roles in nutrient acquisition, microbial competition, and virulence. In this study, we investigated the metabolic consequences of AHL-dependent QS by monitoring the metabolic profile(s) of a lasI rhlI double mutant (unable to make QS signaling molecules) and its wild-type progenitor as they progressed through the growth curve. Analysis of culture supernatants by 1 H-nuclear magnetic resonance ( 1 H-NMR) spectroscopy revealed that at the point where AHL concentrations peaked in the wild type, the metabolic footprints (i.e., extracellular metabolites) of the wild-type and lasI rhlI mutant diverged. Subsequent gas chromatography-mass spectrometry (GC-MS)-based analysis of the intracellular metabolome revealed QS-dependent perturbations in around one-third of all identified metabolites, including altered concentrations of tricarboxylic acid (TCA) cycle intermediates, amino acids, and fatty acids. Further targeted fatty acid methyl ester (FAME) GC-MS-based profiling of the cellular total fatty acid pools revealed that QS leads to changes associated with decreased membrane fluidity and higher chemical stability. However, not all of the changes we observed were necessarily a direct consequence of QS; liquid chromatography (LC)-MS analyses revealed that polyamine levels were elevated in the lasI rhlI mutant, perhaps a response to the absence of QS-dependent adaptations. Our data suggest that QS leads to a global readjustment in central metabolism and provide new insight into the metabolic changes associated with QS during stationary-phase adaptation. IMPORTANCEQuorum sensing (QS) is a transcriptional regulatory mechanism that allows bacteria to coordinate their gene expression profile with the population cell density. The opportunistic human pathogen Pseudomonas aeruginosa uses QS to control the production of secreted virulence factors. In this study, we show that QS elicits a global "metabolic rewiring" in P. aeruginosa. This metabolic rerouting of fluxes is consistent with a variety of drivers, ranging from altered QS-dependent transcription of "metabolic genes" through to the effect(s) of global "metabolic readjustment" as a consequence of QS-dependent exoproduct synthesis, as well as a general stress response, among others. To our knowledge, this is the first study of its kind to assess the global impact of QS on the metabolome. T he gammaproteobacterium Pseudomonas aeruginosa is widely distributed in the environment (1, 2). The organism is a human pathogen and is responsible for a range of acute infections, urinary tract infections, and respiratory infections (3). In addition, it is also associated with certain chronic infections, such as those that often develop in the airways of cystic fibrosis patients (4, 5). Such exquisite adaptability to different niches requires a complex re...

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confidence: 99%

Quorum Sensing Is Accompanied by Global Metabolic Changes in the Opportunistic Human Pathogen Pseudomonas aeruginosa

2015

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“…This phenomenon occurs when the density of bacteria in a specific environment reaches a certain level. Defined as the communication and coordination of the bacterial behavior via the accumulation of signaling molecules, the mechanism relies upon a process such that, when the concentration of these signaling molecules reaches a critical threshold, activation or repression of certain target genes occurs (73). In Gram-negative bacteria, AHLs have been identified as the major signaling molecules in this communication system (68).…”

Section: N-acyl Homoserine Lactones Quorum Sensing and Bacterial Bimentioning

confidence: 99%

Paraoxonases as Potential Antibiofilm Agents: Their Relationship with Quorum-Sensing Signals in Gram-Negative Bacteria

Camps

Pujol

Ballester

et al. 2011

Antimicrob Agents Chemother

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The property of many bacteria to form biofilms constitutes a major health problem. Bacteria living in biofilms have a very high resistance to antibiotics. Biofilms may develop at a certain locations with the participation of secreted molecules, termed quorum-sensing signals, when a sufficient density of bacterial growth occurs. In Gram-negative bacteria, acyl homoserine lactones (AHL) have been identified as major quorum-sensing signals. The paraoxonases (PONs) constitute a family of enzymes comprising 3 members (PON1, PON2, and PON3) that have lactonase activity and are able to hydrolyze AHL. In this minireview, we summarize some existing basic knowledge on PON genetics, biochemistry, and function and describe recent research that reports evidence of the important roles that they may play in the organism's defense against biofilm formation. Finally, we propose some lines of future research that could be very productive.Many bacteria form organized communities of aggregated cells living in hydrated matrices of extracellular polymeric substances. These structures (termed "biofilms") are evolutionary adaptations by bacteria that enable them to survive in hostile environments and to colonize new ecological niches (7, 38). Bacteria living in biofilms have high resistance to antimicrobial agents, which constitutes a major health problem. Hence, investigation of the molecular mechanisms of biofilm formation and the effectiveness of new therapeutic agents in counteracting these mechanisms is becoming a productive line of research. Biofilms may develop with the participation of secreted molecules (termed "quorum-sensing signals") when a sufficiently high density of bacterial growth occurs at a certain location. In Gram-negative bacteria, acyl homoserine lactones (AHLs) have been identified as major quorum-sensing signals. The paraoxonases (PONs) constitute a group of lactonases ubiquitously expressed in human tissues. Recent evidence shows that they may play an important role in the fight against bacterial biofilm formation. In the present minireview, we summarize the current knowledge regarding PONs and their biological function while describing appropriate experiments to elucidate their possible role in antibacterial treatment. WHAT ARE THE PARAOXONASES?The PON enzyme family comprises 3 members, PON1, PON2, and PON3, the genes coding for which are located adjacent to each other on chromosome 7q21-22 (72, 81). In humans, PON1 and PON3 genes are mainly expressed in the liver and kidney and their protein products are found in the circulation bound to high-density lipoprotein (HDL) (45,55,58,79). Conversely, the PON2 gene is expressed a variety of tissues. Its protein product is an intracellular enzyme that is not, however, found in plasma (64). PON1 was first identified in 1953 by Aldridge, who, while examining the rates of hydrolysis of organophosphate insecticides in different tissues of rats and rabbits (5, 6), observed that rabbits exhibited a very high rate of paraoxon degradation in serum and that this compound was...

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“…The term quorum quenching (QQ) was coined to describe numerous enzymatic (32,38) and non-enzymatic (79, 80) signal interference mechanisms, which lead to the disruption of QS, thereby preventing or limiting colonization (81). Some animals and plants have evolved multiple defense mechanisms against bacterial pathogens which are mostly to interfere with the QS system (82).…”

Section: Synthetic Biology and Quorum Quenchingmentioning

confidence: 99%

Microbial linguistics: perspectives and applications of microbial cell-to-cell communication

Mitchell

Lee²,

Kim³

et al. 2011

BMB Reports

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Microbial quorum sensing: a tool or a target for antimicrobial therapy?

Cited by 81 publications

References 220 publications

Quorum Sensing Is Accompanied by Global Metabolic Changes in the Opportunistic Human Pathogen Pseudomonas aeruginosa

Quorum Sensing Is Accompanied by Global Metabolic Changes in the Opportunistic Human Pathogen Pseudomonas aeruginosa

Paraoxonases as Potential Antibiofilm Agents: Their Relationship with Quorum-Sensing Signals in Gram-Negative Bacteria

Microbial linguistics: perspectives and applications of microbial cell-to-cell communication

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