Production of the signalling molecule, autoinducer-2, by Neisseria meningitidis: lack of evidence for a concerted transcriptional response

Microbiology ◽  
2003 ◽  
Vol 149 (7) ◽  
pp. 1859-1869 ◽  
Author(s):  
Joanne E. Dove ◽  
Kazutoyo Yasukawa ◽  
Colin R. Tinsley ◽  
Xavier Nassif
Keyword(s):  
Quorum Sensing ◽  
Neisseria Meningitidis ◽  
Dna Microarrays ◽  
Transcriptional Profiling ◽  
Cell Signalling ◽  
Transcriptional Response ◽  
Autoinducer 2 ◽  
Signalling Molecule ◽  
A Cell ◽  
Quorum Sensing Molecule

Neisseria meningitidis is a Gram-negative bacterium which is an important causative agent of septicaemia and meningitis. LuxS has been shown to be involved in the biosynthesis of a quorum sensing molecule, autoinducer-2 (AI-2), known to play a role in virulence in Escherichia coli, as well as other bacteria. Evidence that serogroup B of N. meningitidis produces AI-2, along with the observation that a luxS mutant of this strain had attenuated virulence in an infant rat model of bacteraemia, led to further investigation of the role of this quorum sensing molecule in N. meningitidis. In this study, it is demonstrated that AI-2 is not involved in regulating growth of meningococci, either in culture or in contact with epithelial cells. Furthermore, transcriptional profiling using DNA microarrays shows an absence of the concerted regulation seen in other bacteria. Taken together, these data suggest that in N. meningitidis, AI-2 may be a metabolic by-product and not a cell-to-cell signalling molecule.

scholarly journals Autoinducer-2 Triggers the Oxidative Stress Response in Mycobacterium avium, Leading to Biofilm Formation

2008 ◽  
Vol 74 (6) ◽  
pp. 1798-1804 ◽  
Author(s):  
Henriette Geier ◽  
Serge Mostowy ◽  
Gerard A. Cangelosi ◽  
Marcel A. Behr ◽  
Timothy E. Ford
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Quorum Sensing ◽  
Mycobacterium Avium ◽  
Biofilm Formation ◽  
Transcriptional Response ◽  
Opportunistic Pathogen ◽  
Environmental Stresses ◽  
Oxidative Stress Response ◽  
Autoinducer 2

ABSTRACT Mycobacterium avium is an environmental organism and opportunistic pathogen with inherent resistance to drugs, environmental stresses, and the host immune response. To adapt to these disparate conditions, M. avium must control its transcriptional response to environmental cues. M. avium forms biofilms in various environmental settings, including drinking water pipes and potable water reservoirs. In this study, we investigated the role of the universal signaling molecule autoinducer-2 (AI-2) in biofilm formation by M. avium. The addition of the compound to planktonic M. avium cultures resulted in increased biofilm formation. Microarray and reverse transcriptase PCR studies revealed an upregulation of the oxidative stress response upon addition of AI-2. This suggests that the response to AI-2 might be related to oxidative stress, rather than quorum sensing. Consistent with this model, addition of hydrogen peroxide, a known stimulus of the oxidative stress response, to M. avium cultures resulted in elevated biofilm formation. These results suggest that AI-2 does not act as a quorum-sensing signal in M. avium. Instead, biofilm formation is triggered by environmental stresses of biotic and abiotic origins and AI-2 may exert effects on that level.

scholarly journals Targeting Quorum Sensing: High-Throughput Screening to Identify Novel LsrK Inhibitors

2019 ◽  
Vol 20 (12) ◽  
pp. 3112 ◽  
Author(s):  
Viviana Gatta ◽  
Polina Ilina ◽  
Alison Porter ◽  
Stuart McElroy ◽  
Päivi Tammela
Keyword(s):  
Quorum Sensing ◽  
High Throughput ◽  
High Throughput Screening ◽  
Enteric Bacteria ◽  
New Class ◽  
Bacterial Pathogenicity ◽  
Autoinducer 2 ◽  
A Cell ◽  
The Moment ◽  
Antivirulence Agents

Since quorum sensing (QS) is linked to the establishment of bacterial infection, its inactivation represents one of the newest strategies to fight bacterial pathogens. LsrK is a kinase playing a key role in the processing of autoinducer-2 (AI-2), a quorum-sensing mediator in gut enteric bacteria. Inhibition of LsrK might thus impair the quorum-sensing cascade and consequently reduce bacterial pathogenicity. Aiming for the development of a target-based assay for the discovery of LsrK inhibitors, we evaluated different assay set-ups based on ATP detection and optimized an automation-compatible method for the high-throughput screening of chemical libraries. The assay was then used to perform the screening of a 2000-compound library, which provided 12 active compounds with an IC50 ≤ 10 µM confirming the effectiveness and sensitivity of our assay. Follow-up studies on the positive hits led to the identification of two compounds, harpagoside and rosolic acid, active in a cell-based AI-2 QS interference assay, which are at the moment the most promising candidates for the development of a new class of antivirulence agents based on LsrK inhibition.

scholarly journals Pseudomonas aeruginosa Las quorum sensing autoinducer suppresses growth and biofilm production in Legionella species

Microbiology ◽  
2009 ◽  
Vol 155 (6) ◽  
pp. 1934-1939 ◽  
Author(s):  
Soichiro Kimura ◽  
Kazuhiro Tateda ◽  
Yoshikazu Ishii ◽  
Manabu Horikawa ◽  
Shinichi Miyairi ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Legionella Pneumophila ◽  
Bacterial Species ◽  
Cell Signalling ◽  
Homoserine Lactone ◽  
Alcaligenes Faecalis ◽  
Suppressive Effect ◽  
Dependent Manner ◽  
A Cell

Bacteria commonly communicate with each other by a cell-to-cell signalling mechanism known as quorum sensing (QS). Recent studies have shown that the Las QS autoinducer N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) of Pseudomonas aeruginosa performs a variety of functions not only in intraspecies communication, but also in interspecies and interkingdom interactions. In this study, we report the effects of Pseudomonas 3-oxo-C12-HSL on the growth and suppression of virulence factors in other bacterial species that frequently co-exist with Ps. aeruginosa in nature. It was found that 3-oxo-C12-HSL, but not its analogues, suppressed the growth of Legionella pneumophila in a dose-dependent manner. However, 3-oxo-C12-HSL did not exhibit a growth-suppressive effect on Serratia marcescens, Proteus mirabilis, Escherichia coli, Alcaligenes faecalis and Stenotrophomonas maltophilia. A concentration of 50 μM 3-oxo-C12-HSL completely inhibited the growth of L. pneumophila. Additionally, a significant suppression of biofilm formation was demonstrated in L. pneumophila exposed to 3-oxo-C12-HSL. Our results suggest that the Pseudomonas QS autoinducer 3-oxo-C12-HSL exerts both bacteriostatic and virulence factor-suppressive activities on L. pneumophila alone.

scholarly journals The role of luxS in Histophilus somni virulence and biofilm formation

2020 ◽  
Author(s):  
Yu Pan ◽  
Shivakumara Siddaramappa ◽  
Indra Sandal ◽  
Allan Dickerman ◽  
Aloka B. Bandara ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Phenotypic Properties ◽  
Autoinducer 2 ◽  
Histophilus Somni ◽  
Signalling Molecule ◽  
The Matrix ◽  
Culture Supernatants

S-ribosylhomocysteinase (LuxS) is required for the synthesis of the autoinducer-2 (AI-2) quorum-sensing signalling molecule in many Gram-negative bacteria. The bovine (and ovine) opportunistic pathogen Histophilus somni contains a luxS, and forms a biofilm containing an exopolysaccharide (EPS) in the matrix. Since biofilm formation is regulated by quorum sensing in many bacteria, the role of luxS in H. somni virulence and biofilm formation was investigated. Although culture supernatants from H. somni were ineffective at inducing bioluminescence in the Vibrio harveyi reporter strain BB170, H. somni luxS complemented the biosynthesis of AI-2 in the luxS-deficient Escherichia coli strain DH5α. H. somni strain 2336 luxS was inactivated by tranposon mutagenesis. Comparison of RNA exression profiles revealed that many genes were significantly differentially expressed in the luxS mutant compared to the wildtype, whether the bacteria were grown planktonically or in a biofilm. Furthermore, the luxS mutant had a truncated and asialylated lipooligosaccharide (LOS), and was substantially more serum-sensitive than the wildtype. Not surprisingly, the luxS mutant was attenuated in a mouse model for H. somni virulence, and some of the altered phenotypes were partially restored after the mutation was complemented with a functional luxS. However, no major differences were observed between the wildtype and the luxS mutant in regard to outer membrane protein profiles, biofilm formation, EPS production, or intracellular survival. These results indicate that luxS plays a role in H. somni virulence in the context of LOS biosynthesis, but not biofilm formation or other phenotypic properties examined.

scholarly journals Growth Deficiencies of Neisseria meningitidis pfs and luxS Mutants Are Not Due to Inactivation of Quorum Sensing

2008 ◽  
Vol 191 (4) ◽  
pp. 1293-1302 ◽  
Author(s):  
Karin Heurlier ◽  
Agnès Vendeville ◽  
Nigel Halliday ◽  
Andrew Green ◽  
Klaus Winzer ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Neisseria Meningitidis ◽  
Growth Conditions ◽  
Growth Defect ◽  
Careful Study ◽  
Wild Type ◽  
Growth Defects ◽  
Autoinducer 2 ◽  
Metabolite Pool ◽  
Metabolic Imbalance

ABSTRACT The activated methyl cycle (AMC) is a central metabolic pathway used to generate (and recycle) several important metabolites and enable methylation. Pfs and LuxS are considered integral components of this pathway because they convert S-adenosylhomocysteine (SAH) to S-ribosylhomocysteine (SRH) and S-ribosylhomocysteine to homocysteine (HCY), respectively. The latter reaction has a second function since it also generates the precursor of the quorum-sensing molecule autoinducer 2 (AI-2). By demonstrating that there was a complete lack of AI-2 production in pfs mutants of the causative agent of meningitis and septicemia, Neisseria meningitidis, we showed that the Pfs reaction is the sole intracellular source of the AI-2 signal. Analysis of lacZ reporters and real-time PCR experiments indicated that pfs is expressed constitutively from a promoter immediately upstream, and careful study of the pfs mutants revealed a growth defect that could not be attributed to a lack of AI-2. Metabolite profiling of the wild type and of a pfs mutant under various growth conditions revealed changes in the concentrations of several AMC metabolites, particularly SRH and SAH and under some conditions also HCY. Similar studies established that an N. meningitidis luxS mutant also has metabolite pool changes and growth defects in line with the function of LuxS downstream of Pfs in the AMC. Thus, the observed growth defect of N. meningitidis pfs and luxS mutants is not due to quorum sensing but is probably due to metabolic imbalance and, in the case of pfs inactivation, is most likely due to toxic accumulation of SAH.

Phosphorylation and Processing of the Quorum-Sensing Molecule Autoinducer-2 in Enteric Bacteria

2007 ◽  
Vol 2 (2) ◽  
pp. 128-136 ◽  
Author(s):  
Karina B. Xavier ◽  
Stephen T. Miller ◽  
Wenyun Lu ◽  
Jeong Hwan Kim ◽  
Joshua Rabinowitz ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Enteric Bacteria ◽  
Autoinducer 2 ◽  
Quorum Sensing Molecule

scholarly journals Quorum Sensing: A Prospective Therapeutic Target for Bacterial Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Qian Jiang ◽  
Jiashun Chen ◽  
Chengbo Yang ◽  
Yulong Yin ◽  
Kang Yao
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Bacterial Diseases ◽  
Autoinducer 2 ◽  
Bacterial Quorum Sensing ◽  
A Cell ◽  
Bacterial Quorum ◽  
Signaling Activation

Bacterial quorum sensing (QS) is a cell-to-cell communication in which specific signals are activated to coordinate pathogenic behaviors and help bacteria acclimatize to the disadvantages. The QS signals in the bacteria mainly consist of acyl-homoserine lactone, autoinducing peptide, and autoinducer-2. QS signaling activation and biofilm formation lead to the antimicrobial resistance of the pathogens, thus increasing the therapy difficulty of bacterial diseases. Anti-QS agents can abolish the QS signaling and prevent the biofilm formation, therefore reducing bacterial virulence without causing drug-resistant to the pathogens, suggesting that anti-QS agents are potential alternatives for antibiotics. This review focuses on the anti-QS agents and their mediated signals in the pathogens and conveys the potential of QS targeted therapy for bacterial diseases.

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