Making Bacteria Behave: New Agonists and Antagonists of Quorum Sensing

Pomianek, Megan E.; Semmelhack, M. F.

doi:10.1021/cb700098c

Cited by 21 publications

(14 citation statements)

References 21 publications

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“…Within a diffusion-limited environment, the local concentration of small molecule cues increases with bacterial population, acting to upregulate virulence genes in opportune situations (i.e., when the population of bacteria is large enough to overwhelm host defenses). 1 QS pathways, therefore, are an attractive target for antimicrobial defense. In the marine environment, QS also contributes to the formation of biofilms by bacteria, the first step in the process of colonization of abiotic surfaces (biofouling).…”

Section: Introductionmentioning

confidence: 99%

Lyngbyoic acid, a “tagged” fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa

et al. 2011

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Quorum sensing (QS) is a mechanism of bacterial gene regulation in response to increases in population density. Perhaps most studied are QS pathways mediated by acylhomoserine lactones (AHLs) in Gram-negative bacteria. Production of small molecule QS signals, their accumulation within a diffusion-limited environment and their binding to a LuxR-type receptor trigger QS-controlled gene regulatory cascades. In Pseudomonas aeruginosa, for example, binding of AHLs to their cognate receptors (LasR, RhlR) controls production of virulence factors, pigments, antibiotics and other behaviors important for its interactions with eukaryotic hosts and other bacteria. We have previously shown that marine cyanobacteria produce QS-inhibitory molecules, including 8-epi-malyngamide C (1), malyngamide C (2) and malyngolide (3). Here we isolated a new small cyclopropane-containing fatty acid, lyngbyoic acid (4), as a major metabolite of the marine cyanobacterium, Lyngbya cf. majuscula, collected at various sites in Florida. We screened 4 against four reporters based on different AHL receptors (LuxR, AhyR, TraR and LasR) and found that 4 most strongly affected LasR. We also show that 4 reduces pyocyanin and elastase (LasB) both on the protein and transcript level in wild-type P. aeruginosa, and that 4 directly inhibits LasB enzymatic activity. Conversely, dodecanoic acid (9) increased pyocyanin and LasB, demonstrating that the fused cyclopropane “tag” is functionally relevant and potentially confers resistance to β-oxidation. Global transcriptional effects of 4 in some ways replicate the gene expression changes of P. aeruginosa during chronic lung infections of cystic fibrosis patients, with reduced lasR signaling, increased biofilm and expression of the virulence locus HSI-I. Compound 4 may therefore prove to be a useful tool in the study of P. aeruginosa adaption during such chronic infections.

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Section: Introductionmentioning

confidence: 99%

Lyngbyoic acid, a “tagged” fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa

et al. 2011

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“…We were also interested in the potential for 1 and malyngamide C to act on bacterial quorum sensing (QS) pathways. These pathways allow bacteria to regulate their behavior according to their own population density 30. QS regulated behaviors include the expression of virulence factors and the onset of hardy biofilm phenotypes 30.…”

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confidence: 99%

“…These pathways allow bacteria to regulate their behavior according to their own population density 30. QS regulated behaviors include the expression of virulence factors and the onset of hardy biofilm phenotypes 30. One group of compounds that are used for QS signaling are the acyl homoserine lactones, which all contain a five-membered lactone ring joined by an amide linkage to a fatty acid chain 31.…”

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confidence: 99%

Isolation and Biological Evaluation of 8-epi-Malyngamide C from the Floridian Marine Cyanobacterium Lyngbya majuscula

et al. 2010

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A new stereoisomer of malyngamide C, 8-epi-malyngamide C (1), and the known compound lyngbic acid [(4E,7S)-7-methoxytetradec-4-enoic acid] were isolated from a sample of Lyngbya majuscula collected near Bush Key, Dry Tortugas, Florida. The structure of 1 was determined by NMR and MS experiments. The absolute configuration of 1 was determined by selective Mitsunobu inversion of C-8 to give malyngamide C, as determined by NMR, MS, and comparison of specific rotation. Both 1 and malyngamide C were found to be cytotoxic to HT29 colon cancer cells (IC50 15.4 μM and 5.2 μM, respectively) and to inhibit bacterial quorum sensing in a reporter gene assay.

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“…(ii) Secondly, several small molecules that mimic or deactivate the complex interactions between the signaling molecule and their protein receptors were identified [168]. A distinction is made between an agonist, implying a function like the native AHL based on the mimic structure and an antagonist blocking the receptor binding site prevents binding of the signaling molecule [169]. For instance, an AHL agonist for P. aeruginosa was identified, which shows no obvious structural connection to the AHL (3-oxo-C12-HSL) but was predicted to bind in the same protein pocket of the receptor protein as the AHL [170].…”

Section: Bacterial Communication-quorum Sensingmentioning

confidence: 99%

Friends or Foes—Microbial Interactions in Nature

Weiland‐Bräuer

2021

Biology

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Microorganisms are present in nearly every niche on Earth and mainly do not exist solely but form communities of single or mixed species. Within such microbial populations and between the microbes and a eukaryotic host, various microbial interactions take place in an ever-changing environment. Those microbial interactions are crucial for a successful establishment and maintenance of a microbial population. The basic unit of interaction is the gene expression of each organism in this community in response to biotic or abiotic stimuli. Differential gene expression is responsible for producing exchangeable molecules involved in the interactions, ultimately leading to community behavior. Cooperative and competitive interactions within bacterial communities and between the associated bacteria and the host are the focus of this review, emphasizing microbial cell–cell communication (quorum sensing). Further, metagenomics is discussed as a helpful tool to analyze the complex genomic information of microbial communities and the functional role of different microbes within a community and to identify novel biomolecules for biotechnological applications.

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Making Bacteria Behave: New Agonists and Antagonists of Quorum Sensing

Cited by 21 publications

References 21 publications

Lyngbyoic acid, a “tagged” fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa

Lyngbyoic acid, a “tagged” fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa

Isolation and Biological Evaluation of 8-epi-Malyngamide C from the Floridian Marine Cyanobacterium Lyngbya majuscula

Friends or Foes—Microbial Interactions in Nature

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