scholarly journals The role of 2,4-dihydroxyquinoline (DHQ) inPseudomonas aeruginosapathogenicity

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1495 ◽  
Author(s):  
Jordon D. Gruber ◽  
Wei Chen ◽  
Stuart Parnham ◽  
Kevin Beauchesne ◽  
Peter Moeller ◽  
...  

Bacteria synchronize group behaviors using quorum sensing, which is advantageous during an infection to thwart immune cell attack and resist deleterious changes in the environment. InPseudomonas aeruginosa, thePseudomonasquinolone signal (Pqs) quorum-sensing system is an important component of an interconnected intercellular communication network. Two alkylquinolones, 2-heptyl-4-quinolone (HHQ) and 2-heptyl-3-hydroxy-4-quinolone (PQS), activate transcriptional regulator PqsR to promote the production of quinolone signals and virulence factors. Our work focused on the most abundant quinolone produced from the Pqs system, 2,4-dihydroxyquinoline (DHQ), which was shown previously to sustain pyocyanin production and antifungal activity ofP. aeruginosa. However, little is known about how DHQ affectsP. aeruginosapathogenicity. UsingC. elegansas a model forP. aeruginosainfection, we foundpqsmutants only able to produce DHQ maintained virulence towards the nematodes similar to wild-type. In addition, DHQ-only producing mutants displayed increased colonization ofC. elegansand virulence factor production compared to a quinolone-null strain. DHQ also bound to PqsR and activated the transcription ofpqsoperon. More importantly, high extracellular concentration of DHQ was maintained in both aerobic and anaerobic growth. High levels of DHQ were also detected in the sputum samples of cystic fibrosis patients. Taken together, our findings suggest DHQ may play an important role in sustainingP. aeruginosapathogenicity under oxygen-limiting conditions.

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Yingchao Zhang ◽  
Chuan-min Zhou ◽  
Qinqin Pu ◽  
Qun Wu ◽  
Shirui Tan ◽  
...  

ABSTRACT Pseudomonas aeruginosa, one of the most common pathogens in hospital-acquired infections, is tightly controlled by a multilayered regulatory network, including the quorum sensing system (QS), the type VI secretion system (T6SS), and resistance to host immunity. We found that the P. aeruginosa 3880 (PA3880) gene, which encodes an unknown protein, acts as a regulator of anaerobic metabolism in response to oxidative stress and virulence in P. aeruginosa. More than 30 PA3880 homologs were found in other bacterial genomes, indicating that PA3880 is widely distributed in the Bacteria kingdom as a highly conserved gene. Deletion of the PA3880 gene changed the expression levels of more than 700 genes, including a group of virulence genes, under both aerobic and anaerobic conditions. To further study the mechanisms of PA3880-mediated regulation in virulence, we utilized a bacterial two-hybrid assay and found that the PA3880 protein interacted directly with QS regulator MvfR and anaerobic regulator Anr. Loss of the PA3880 protein significantly blunted the pathogenicity of P. aeruginosa, resulting in increased host survival, decreased bacterial burdens, reduced inflammatory responses, and fewer lung injuries in challenged mice hosts. Mechanistically, we found that Cys44 was a critical site for the full function of PA3880 in influencing alveolar macrophage phagocytosis and bacterial clearance. We also found that AnvM directly interacted with host receptors Toll-like receptor 2 (TLR2) and TLR5, which might lead to activation of the host immune response. Hence, we gave the name AnvM (anaerobic and virulence modulator) to the PA3880 protein. This characterization of AnvM could help to uncover new targets and strategies to treat P. aeruginosa infections. IMPORTANCE Infections by Pseudomonas aeruginosa, one of the most frequently isolated human pathogens, can create huge financial burdens. However, knowledge of the molecular mechanisms involved in the pathogenesis of P. aeruginosa remains elusive. We identified AnvM as a novel regulator of virulence in P. aeruginosa. Deletion of anvM altered the expression levels of more than 700 genes under aerobic and anaerobic conditions, including quorum sensing system genes and oxidative stress resistance genes. AnvM directly interacted with MvfR and Anr, thus regulating their downstream genes. More importantly, AnvM directly bound to TLR2 and TLR5, which turn on the host immune response. These findings provide insights into the significance of AnvM homologs in pathogenic bacteria and suggest a potential drug target against bacterial infection.


2011 ◽  
Vol 79 (10) ◽  
pp. 4050-4060 ◽  
Author(s):  
Jorge E. Vidal ◽  
Herbert P. Ludewick ◽  
Rebekah M. Kunkel ◽  
Dorothea Zähner ◽  
Keith P. Klugman

ABSTRACTStreptococcus pneumoniaeis the leading cause of death in children worldwide and forms highly organized biofilms in the nasopharynx, lungs, and middle ear mucosa. TheluxS-controlled quorum-sensing (QS) system has recently been implicated in virulence and persistence in the nasopharynx, but its role in biofilms has not been studied. Here we show that this QS system plays a major role in the control ofS. pneumoniaebiofilm formation. Our results demonstrate that theluxSgene is contained by invasive isolates and normal-flora strains in a region that contains genes involved in division and cell wall biosynthesis. TheluxSgene was maximally transcribed, as a monocistronic message, in the early mid-log phase of growth, and this coincides with the appearance of early biofilms. Demonstrating the role of the LuxS system in regulatingS. pneumoniaebiofilms, at 24 h postinoculation, two different D39ΔluxSmutants produced ∼80% less biofilm biomass than wild-type (WT) strain D39 did. Complementation of these strains withluxS, either in a plasmid or integrated as a single copy in the genome, restored their biofilm level to that of the WT. Moreover, a soluble factor secreted by WT strain D39 or purified AI-2 restored the biofilm phenotype of D39ΔluxS. Our results also demonstrate that during the early mid-log phase of growth, LuxS regulates the transcript levels oflytA, which encodes an autolysin previously implicated in biofilms, and also the transcript levels ofply, which encodes the pneumococcal pneumolysin. In conclusion, theluxS-controlled QS system is a key regulator of early biofilm formation byS. pneumoniaestrain D39.


Minerals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 222 ◽  
Author(s):  
Xue-Yan Gao ◽  
Xiu-Jie Liu ◽  
Chang-Ai Fu ◽  
Xiu-Feng Gu ◽  
Jian-Qiang Lin ◽  
...  

Acidithiobacillus ferrooxidans is an acidophilic and chemolithotrophic sulfur- and iron-oxidizing bacterium that has been widely used in the bioleaching process for extracting metals. Extracellular polymeric substances (EPS) are essential for bacteria-ore interactions, and the regulation of EPS synthesis could be an important way of influencing the efficiency of the bioleaching process. Therefore, exploring and utilizing the regulatory pathways of EPS synthesis to improve the bacterial bioleaching capability have posed a challenge in the study and application of bioleaching bacteria. Here, several engineering strains were constructed using genetic manipulation methods. And we revealed the regulatory function of the AfeI/R quorum sensing (QS) system in EPS synthesis and biofilm formation of A. ferrooxidans, and the AfeI/R-mediated EPS synthesis could influence bacteria-substrate interactions and the efficiency of bioleaching. Finally, an AfeI/R-mediated bioleaching model was proposed to illustrate the role of QS system in this process. This study provided new insights into and clues for developing highly efficient bioleaching bacteria and modulating the bioleaching process.


2013 ◽  
Vol 79 (14) ◽  
pp. 4421-4432 ◽  
Author(s):  
B. G. Coutinho ◽  
B. Mitter ◽  
C. Talbi ◽  
A. Sessitsch ◽  
E. J. Bedmar ◽  
...  

2007 ◽  
Vol 189 (13) ◽  
pp. 4969-4972 ◽  
Author(s):  
Masanori Toyofuku ◽  
Nobuhiko Nomura ◽  
Tatsuya Fujii ◽  
Naoki Takaya ◽  
Hideaki Maseda ◽  
...  

ABSTRACT Anaerobic growth of Pseudomonas aeruginosa PAO1 was affected by quorum sensing. Deletion of genes that produce N-acyl-l-homoserine lactone signals resulted in an increase in denitrification activity, which was repressed by exogenous signal molecules. The effect of the las quorum-sensing system was dependent on the rhl quorum-sensing system in regulating denitrification.


2002 ◽  
Vol 70 (8) ◽  
pp. 4678-4681 ◽  
Author(s):  
Eleftherios Mylonakis ◽  
Michael Engelbert ◽  
Xiang Qin ◽  
Costi D. Sifri ◽  
Barbara E. Murray ◽  
...  

ABSTRACT We used a rabbit endophthalmitis model to explore the role of fsrB, a gene required for the function of the fsr quorum-sensing system of Enterococcus faecalis, in pathogenicity. A nonpolar deletion mutant of fsrB had significantly reduced virulence compared to wild type. Complementation of mutation restored virulence. These data corroborate the role of fsrB in E. faecalis pathogenesis and suggest that the rabbit endophthalmitis model can be used to study the in vivo role of quorum sensing.


2003 ◽  
Vol 185 (1) ◽  
pp. 325-331 ◽  
Author(s):  
Melanie M. Marketon ◽  
Sarah A. Glenn ◽  
Anatol Eberhard ◽  
Juan E. González

ABSTRACT Sinorhizobium meliloti is a soil bacterium capable of invading and establishing a symbiotic relationship with alfalfa plants. This invasion process requires the synthesis, by S. meliloti, of at least one of the two symbiotically important exopolysaccharides, succinoglycan and EPS II. We have previously shown that the sinRI locus of S. meliloti encodes a quorum-sensing system that plays a role in the symbiotic process. Here we show that the sinRI locus exerts one level of control through regulation of EPS II synthesis. Disruption of the autoinducer synthase gene, sinI, abolished EPS II production as well as the expression of several genes in the exp operon that are responsible for EPS II synthesis. This phenotype was complemented by the addition of acyl homoserine lactone (AHL) extracts from the wild-type strain but not from a sinI mutant, indicating that the sinRI-specified AHLs are required for exp gene expression. This was further confirmed by the observation that synthetic palmitoleyl homoserine lactone (C16:1-HL), one of the previously identified sinRI-specified AHLs, specifically restored exp gene expression. Most importantly, the absence of symbiotically active EPS II in a sinI mutant was confirmed in plant nodulation assays, emphasizing the role of quorum sensing in symbiosis.


2009 ◽  
Vol 75 (11) ◽  
pp. 3808-3812 ◽  
Author(s):  
Nina M. Talyzina ◽  
Pär K. Ingvarsson ◽  
Jun Zhu ◽  
Sun N. Wai ◽  
Agneta Andersson

ABSTRACT Two haplotypes of the Vibrio cholerae quorum-sensing system regulator hapR are described: hapR1, common among nonpandemic, non-O1, non-O139 strains, and hapR2, associated with pandemic O1 and O139 and epidemic O37 V. cholerae strains. The hapR2 has evolved under strong natural selection, implying that its fixation was influenced by conditions that led to cholera pandemics.


2000 ◽  
Vol 182 (10) ◽  
pp. 2702-2708 ◽  
Author(s):  
Susan L. McKnight ◽  
Barbara H. Iglewski ◽  
Everett C. Pesci

ABSTRACT The opportunistic pathogen Pseudomonas aeruginosa uses intercellular signals to control the density-dependent expression of many virulence factors. The las and rhlquorum-sensing systems function, respectively, through the autoinducersN-(3-oxododecanoyl)-l-homoserine lactone andN-butyryl-l-homoserine lactone (C4-HSL), which are known to positively regulate the transcription of the elastase-encoding gene, lasB. Recently, we reported that a second type of intercellular signal is involved in lasB induction. This signal was identified as 2-heptyl-3-hydroxy-4-quinolone and designated thePseudomonas quinolone signal (PQS). PQS was determined to be part of the quorum-sensing hierarchy since its production and bioactivity depended on the las and rhlquorum-sensing systems, respectively. In order to define the role of PQS in the P. aeruginosa quorum-sensing cascade,lacZ gene fusions were used to determine the effect of PQS on the transcription of the quorum-sensing system geneslasR, lasI, rhlR, andrhlI. We found that in P. aeruginosa, PQS caused a major induction of rhlI′-lacZ and had lesser effects on the transcription of lasR′-lacZ andrhlR′-lacZ. We also observed that the transcription of bothrhlI′-lacZ and lasB′-lacZ was cooperatively effected by C4-HSL and PQS. Additionally, we present data indicating that PQS was not produced maximally until cultures reached the late stationary phase of growth. Taken together, our results imply that PQS acts as a link between the las and rhlquorum-sensing systems and that this signal is not involved in sensing cell density.


2014 ◽  
Vol 55 (5) ◽  
pp. 671-678 ◽  
Author(s):  
Jingming Zhao ◽  
Handong Jiang ◽  
Wei Cheng ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  

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