Mechanism underlying autoinducer recognition in the<i>Vibrio cholerae</i>DPO-VqmA quorum-sensing pathway

Huang, Xiangyan; Duddy, Olivia P.; Silpe, Justin E.; Paczkowski, Jon P; Cong, Jian-Ping; Henke, Brad R.; Bassler, Bonnie L.

doi:10.1101/2019.12.19.881847

Cited by 4 publications

(6 citation statements)

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“…In the context of detection by the V. harveyi quorum-sensing apparatus, the EC50 for AI-2 is 3 nM and that for MHF is 300 nM ( Figure 2B). Thus, while both compounds exert activity in this system within the range reported for bacterial AIs (33)(34)(35)(36), the LuxP receptor prefers AI-2 over MHF.…”

Section: Mhf Agonizes Luxp With a Nanomolar Ec50supporting

confidence: 54%

Saccharomyces cerevisiaeRequiresCFF1to Produce 4-hydroxy-5-methylfuran-3(2H)-one, a Mimic of the Bacterial Quorum-Sensing Autoinducer AI-2

Valastyan

Kraml

Pelczer

et al. 2020

Preprint

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Quorum sensing is a process of cell-to-cell communication that bacteria use to orchestrate collective behaviors. Quorum sensing depends on the production, release, and detection of extracellular signal molecules called autoinducers (AIs) that accumulate with increasing cell density. While most AIs are species-specific, the AI called AI-2 is produced and detected by diverse bacterial species and it mediates inter-species communication. We recently reported that mammalian cells produce an AI-2 mimic that can be detected by bacteria through the AI-2 receptor, LuxP, potentially expanding the role of the AI-2 system to inter-domain communication. Here, we describe a second molecule capable of inter-domain signaling through LuxP, 4-hydroxy-5-methylfuran-3(2H)-one (MHF) that is produced by the yeast Saccharomyces cerevisiae. Screening the S. cerevisiae deletion collection revealed Cff1p, a protein with no known role, to be required for MHF production. Cff1p is proposed to be an enzyme, possibly an epimerase or isomerase, and substitution at the putative catalytic residue eliminated MHF production in S. cerevisiae. Sequence analysis uncovered Cff1p homologs in many species, primarily bacterial and fungal, but also viral, archaeal, and higher eukaryotic. Cff1p homologs from organisms from all domains can complement a S. cerevisiae cff1Δ mutant and restore MHF production. In all test cases, the identified catalytic residue is conserved and required for MHF to be produced. These findings increase the scope of possibilities for inter-domain interactions via AI-2 and AI-2 mimics, highlighting the breadth of molecules and organisms that could participate in quorum sensing.ImportanceQuorum sensing is a cell-to-cell communication process that bacteria use to monitor local population density. Quorum sensing relies on extracellular signal molecules called autoinducers (AIs). One AI, called AI-2, is broadly made by bacteria and used for inter-species communication. Here, we describe a eukaryotic AI-2 mimic, 5-methylfuran-3(2H)-one, (MHF), that is made by the yeast Saccharomyces cerevisiae, and we identify the Cff1p protein as essential for MHF production. Hundreds of viral, archaeal, bacterial, and eukaryotic organisms possess Cff1p homologs. This finding, combined with our results showing that homologs from all domains can replace S. cerevisiae Cff1p, suggests that like AI-2, MHF is widely produced. Our results expand the breadth of organisms that may participate in quorum-sensing-mediated interactions.

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Section: Mhf Agonizes Luxp With a Nanomolar Ec50supporting

confidence: 54%

Saccharomyces cerevisiaeRequiresCFF1to Produce 4-hydroxy-5-methylfuran-3(2H)-one, a Mimic of the Bacterial Quorum-Sensing Autoinducer AI-2

Valastyan

Kraml

Pelczer

et al. 2020

Preprint

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“…pET15b plasmids encoding 6×His-VqmA were mobilized into Δ tdh E. coli BL21(DE3). Strains were cultured for protein production as described previously ( 15 , 16 ). Cells were harvested by centrifugation, and pellets were resuspended in 1/100 volume of lysis buffer (50 mM Tris, 150 mM NaCl, pH 7.5, containing 0.5 mg/ml lysozyme, 1× protease inhibitor, and benzonase) for 5 min followed by the addition of an equal volume of Bugbuster reagent (Novagen).…”

Section: Methodsmentioning

confidence: 99%

“…In the case of CAI-1 and AI-2 detection, the reporter strains carried a plasmid encoding the Vibrio harveyi luxCDABE (luciferase) operon ( 2 ). For DPO detection, the reporter strain possessed a p vqmR-lux (luciferase) fusion on the chromosome in place of the native lacZ locus ( 16 ). Genotypes are provided in Table S1 in the supplemental material.…”

Section: Methodsmentioning

confidence: 99%

“…DPO is detected by the cytoplasmic VqmA receptor-transcription factor that activates expression of vqmR , encoding the VqmR regulatory small RNA (sRNA) ( 11 , 14 , 15 ). Both Apo- and DPO-bound-VqmA (Holo-VqmA) can activate vqmR expression with Holo-VqmA being more potent than Apo-VqmA ( 16 ). VqmR posttranscriptionally regulates target mRNAs ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

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The Vibrio cholerae Quorum-Sensing Protein VqmA Integrates Cell Density, Environmental, and Host-Derived Cues into the Control of Virulence

Mashruwala

Bassler

2020

mBio

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Quorum sensing is a chemical communication process in which bacteria use the production, release, and detection of signal molecules called autoinducers to orchestrate collective behaviors. The human pathogen Vibrio cholerae requires quorum sensing to infect the small intestine. There, V. cholerae encounters the absence of oxygen and the presence of bile salts. We show that these two stimuli differentially affect quorum-sensing function and, in turn, V. cholerae pathogenicity. First, during anaerobic growth, V. cholerae does not produce the CAI-1 autoinducer, while it continues to produce the DPO autoinducer, suggesting that CAI-1 may encode information specific to the aerobic lifestyle of V. cholerae. Second, the quorum-sensing receptor-transcription factor called VqmA, which detects the DPO autoinducer, also detects the lack of oxygen and the presence of bile salts. Detection occurs via oxygen-, bile salt-, and redox-responsive disulfide bonds that alter VqmA DNA binding activity. We propose that VqmA serves as an information processing hub that integrates quorum-sensing information, redox status, the presence or absence of oxygen, and host cues. In response to the information acquired through this mechanism, V. cholerae appropriately modulates its virulence output. IMPORTANCE Quorum sensing (QS) is a process of chemical communication that bacteria use to orchestrate collective behaviors. QS communication relies on chemical signal molecules called autoinducers. QS regulates virulence in Vibrio cholerae, the causative agent of the disease cholera. Transit into the human small intestine, the site of cholera infection, exposes V. cholerae to the host environment. In this study, we show that the combination of two stimuli encountered in the small intestine, the absence of oxygen and the presence of host-produced bile salts, impinge on V. cholerae QS function and, in turn, pathogenicity. We suggest that possessing a QS system that is responsive to multiple environmental, host, and cell density cues enables V. cholerae to fine-tune its virulence capacity in the human intestine.

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“…VqmR small RNA in turn post-transcriptionally controls many target genes by repressing translation of ctx, rtxA, vpsT , and aphA . vpsT encodes component required for biofilm formation and aphA , encodes the low cell density QS master regulator AphA (Huang et al, 2020 ).…”

Section: Role Of Quorum Sensing (Qs) and Biofilm Formationmentioning

confidence: 99%

Virulence Regulation and Innate Host Response in the Pathogenicity of Vibrio cholerae

Ramamurthy

Nandy

Mukhopadhyay

et al. 2020

Front. Cell. Infect. Microbiol.

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The human pathogen Vibrio cholerae is the causative agent of severe diarrheal disease known as cholera. Of the more than 200 "O" serogroups of this pathogen, O1 and O139 cause cholera outbreaks and epidemics. The rest of the serogroups, collectively known as non-O1/non-O139 cause sporadic moderate or mild diarrhea and also systemic infections. Pathogenic V. cholerae circulates between nutrient-rich human gut and nutrient-deprived aquatic environment. As an autochthonous bacterium in the environment and as a human pathogen, V. cholerae maintains its survival and proliferation in these two niches. Growth in the gastrointestinal tract involves expression of several genes that provide bacterial resistance against host factors. An intricate regulatory program involving extracellular signaling inputs is also controlling this function. On the other hand, the ability to store carbon as glycogen facilitates bacterial fitness in the aquatic environment. To initiate the infection, V. cholerae must colonize the small intestine after successfully passing through the acid barrier in the stomach and survive in the presence of bile and antimicrobial peptides in the intestinal lumen and mucus, respectively. In V. cholerae, virulence is a multilocus phenomenon with a large functionally associated network. More than 200 proteins have been identified that are functionally linked to the virulence-associated genes of the pathogen. Several of these genes have a role to play in virulence and/or in functions that have importance in the human host or the environment. A total of 524 genes are differentially expressed in classical and El Tor strains, the two biotypes of V. cholerae serogroup O1. Within the host, many immune and biological factors are able to induce genes that are responsible for survival, colonization, and virulence. The innate host immune response to V. cholerae infection includes activation of several immune protein complexes, receptor-mediated signaling pathways, and other bactericidal proteins. This article presents an overview of regulation of important virulence factors in V. cholerae and host response in the context of pathogenesis.

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Mechanism underlying autoinducer recognition in theVibrio choleraeDPO-VqmA quorum-sensing pathway

Cited by 4 publications

References 47 publications

Saccharomyces cerevisiaeRequiresCFF1to Produce 4-hydroxy-5-methylfuran-3(2H)-one, a Mimic of the Bacterial Quorum-Sensing Autoinducer AI-2

Saccharomyces cerevisiaeRequiresCFF1to Produce 4-hydroxy-5-methylfuran-3(2H)-one, a Mimic of the Bacterial Quorum-Sensing Autoinducer AI-2

The Vibrio cholerae Quorum-Sensing Protein VqmA Integrates Cell Density, Environmental, and Host-Derived Cues into the Control of Virulence

Virulence Regulation and Innate Host Response in the Pathogenicity of Vibrio cholerae

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