scholarly journals Two Distinct Pathways Supply Anthranilate as a Precursor of the Pseudomonas Quinolone Signal

2007 ◽  
Vol 189 (9) ◽  
pp. 3425-3433 ◽  
Author(s):  
John M. Farrow ◽  
Everett C. Pesci

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections in immunocompromised patients and those with cystic fibrosis (CF). This gram-negative bacterium uses multiple cell-to-cell signals to control numerous cellular functions and virulence. One of these signals is 2-heptyl-3-hydroxy-4-quinolone, which is referred to as the Pseudomonas quinolone signal (PQS). This signal functions as a coinducer for a transcriptional regulator (PqsR) to positively control multiple virulence genes and its own synthesis. PQS production is required for virulence in multiple models of infection, and it has been shown to be produced in the lungs of CF patients infected by P. aeruginosa. One of the precursor compounds from which PQS is synthesized is the metabolite anthranilate. This compound can be derived from the conversion of chorismate to anthranilate by an anthranilate synthase or through the degradation of tryptophan via the anthranilate branch of the kynurenine pathway. In this study, we present data which help to define the kynurenine pathway in P. aeruginosa and show that the kynurenine pathway serves as a critical source of anthranilate for PQS synthesis. We also show that the kyn pathway genes are induced during growth with tryptophan and that they are autoregulated by kynurenine. This study provides solid foundations for the understanding of how P. aeruginosa produces the anthranilate that serves as a precursor to PQS and other 4-quinolones.

2005 ◽  
Vol 73 (2) ◽  
pp. 878-882 ◽  
Author(s):  
M. Worth Calfee ◽  
John G. Shelton ◽  
James A. McCubrey ◽  
Everett C. Pesci

ABSTRACT Pseudomonas aeruginosa is a gram-negative bacterium that causes serious infections in immunocompromised individuals and cystic fibrosis patients. This opportunistic pathogen controls many of its virulence factors and cellular functions through the activity of three cell-to-cell signals, N-(3-oxododecanoyl)-l-homoserine lactone, N-butyryl-l-homoserine lactone, and the Pseudomonas quinolone signal (PQS). The activity of these signals is dependent upon their ability to dissolve in and freely diffuse through the aqueous solution in which P. aeruginosa happens to reside. Despite this, our data indicated that PQS was relatively insoluble in aqueous solutions, which led us to postulate that P. aeruginosa could be producing a PQS-solubilizing factor. In this report, we show that the P. aeruginosa-produced biosurfactant rhamnolipid greatly enhances the solubility of PQS in aqueous solutions. The enhanced solubility of PQS led to an increase in PQS bioactivity, as measured by both a gene induction assay and an apoptosis assay. This is the first demonstration of the importance of a bacterial surfactant in the solubilization and bioactivity of a cell-to-cell signal.


2015 ◽  
Vol 197 (12) ◽  
pp. 1988-2002 ◽  
Author(s):  
John M. Farrow ◽  
L. Lynn Hudson ◽  
Greg Wells ◽  
James P. Coleman ◽  
Everett C. Pesci

ABSTRACTPseudomonas aeruginosais a Gram-negative bacterium that is ubiquitous in the environment, and it is an opportunistic pathogen that can infect a variety of hosts, including humans. During the process of infection,P. aeruginosacoordinates the expression of numerous virulence factors through the production of multiple cell-to-cell signaling molecules. The production of these signaling molecules is linked through a regulatory network, with the signalN-(3-oxododecanoyl) homoserine lactone and its receptor LasR controlling the induction of a second acyl-homoserine lactone signal and thePseudomonasquinolone signal (PQS). LasR-mediated control of PQS occurs partly by activating the transcription ofpqsR, a gene that encodes the PQS receptor and is necessary for PQS production. We show that LasR interacts with a single binding site in thepqsRpromoter region and that it does not influence the transcription of the divergently transcribed gene,nadA. Using DNA affinity chromatography, we identified additional proteins that interact with thepqsR-nadAintergenic region. These include the H-NS family members MvaT and MvaU, and CysB, a transcriptional regulator that controls sulfur uptake and cysteine biosynthesis. We show that CysB interacts with thepqsRpromoter and that CysB repressespqsRtranscription and PQS production. Additionally, we provide evidence that CysB can interfere with the activation ofpqsRtranscription by LasR. However, as seen with other CysB-regulated genes,pqsRexpression was not differentially regulated in response to cysteine levels. These findings demonstrate a novel role for CysB in influencing cell-to-cell signal production byP. aeruginosa.IMPORTANCEThe production of PQS and other 4-hydroxy-2-alkylquinolone (HAQs) compounds is a key component of theP. aeruginosacell-to-cell signaling network, impacts multiple physiological functions, and is required for virulence. PqsR directly regulates the genes necessary for HAQ production, but little is known about the regulation ofpqsR. We identified CysB as a novel regulator ofpqsRand PQS production, but, unlike other CysB-controlled genes, it does not appear to regulatepqsRin response to cysteine. This implies that CysB functions as both a cysteine-responsive and cysteine-unresponsive regulator inP. aeruginosa.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 630
Author(s):  
Diaa Alrahmany ◽  
Ahmed F. Omar ◽  
Gehan Harb ◽  
Wasim S. El El Nekidy ◽  
Islam M. Ghazi

Background Acinetobacter baumannii (AB), an opportunistic pathogen, could develop into serious infections with high mortality and financial burden. The debate surrounding the selection of effective antibiotic treatment necessitates studies to define the optimal approach. This study aims to compare the clinical outcomes of commonly used treatment regimens in hospitalized patients


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jennifer M. Peña ◽  
Samantha M. Prezioso ◽  
Kirsty A. McFarland ◽  
Tracy K. Kambara ◽  
Kathryn M. Ramsey ◽  
...  

AbstractIn Pseudomonas aeruginosa the alp system encodes a programmed cell death pathway that is switched on in a subset of cells in response to DNA damage and is linked to the virulence of the organism. Here we show that the central regulator of this pathway, AlpA, exerts its effects by acting as an antiterminator rather than a transcription activator. In particular, we present evidence that AlpA positively regulates the alpBCDE cell lysis genes, as well as genes in a second newly identified target locus, by recognizing specific DNA sites within the promoter, then binding RNA polymerase directly and allowing it to bypass intrinsic terminators positioned downstream. AlpA thus functions in a mechanistically unusual manner to control the expression of virulence genes in this opportunistic pathogen.


2021 ◽  
Author(s):  
Jonathan Hira ◽  
Klara Stensvåg

Abstract “Sea urchin lesion syndrome” is known as sea urchins disease with the progressive development of necrotic epidermal tissue and loss of external organs, including appendages on the outer body surface. Recently, a novel strain, Vibrio echinoideorum has been isolated from the lesions of green sea urchin (Strongylocentrotus droebachiensis), an economically important mariculture species in Norway. V. echinoideorum has not been reported elsewhere in association of with green sea urchin lesion syndrome. Therefore, in this study, an immersion based bacterial challenge experiment was performed to expose sea urchins (wounded and non-wounded) to V. echinoideorum, thereby mimicking a nearly natural host-pathogen interaction under controlled conditions. This infection experiment demonstrated that only the injured sea urchins developed the lesion to a significant degree when exposed to V. echinoideorum. Pure cultures of the employed bacterial strain was recovered from the infected animals and its identity was confirmed by the MALDI-TOF MS spectra profiling. Additionally, the hemolytic phenotype of V. echinoideorum substantiated its virulence potential towards the host, and this was also supported by the cytolytic effect on red spherule cells of sea urchins. Furthermore, the genome sequence of V. echinoideorum was assumed to encode potential virulence genes and were subjected for in silico comparison with the established virulence factors of Vibrio vulnificus and Vibrio tasmaniensis. This comparative virulence profile provided novel insights about virulence genes and their putative functions related to chemotaxis, adherence, invasion, evasion of the host immune system, and damage of host tissue and cells. Thus, it supports the pathogenicity of V. echinoideorum. In conclusion, the interaction of V. echinoideorum with injured sea urchins appears to be essential for the development of lesion syndrome and therefore, revealing its potentiality as an opportunistic pathogen.


2004 ◽  
Vol 53 (11) ◽  
pp. 1069-1073 ◽  
Author(s):  
Elisa Bittencourt de Marques ◽  
Sérgio Suzart

Epidemiological studies have reinforced the importance of Enterococcus faecalis in causing serious infections, and to date, our understanding of how certain virulence factors are involved in the pathogenesis of enterococcal infections is still limited. The aim of the present study was to examine the occurrence of known virulence determinants in a group of E. faecalis strains isolated from different clinical sources in Brazil. A total of 95 E. faecalis strains were investigated for the presence of nine virulence genes including aggA, cylA, cylB, cylM, eep, efaA, enlA, esp and gelE by using PCR. The data showed a relatively wide distribution of the virulence genes among the investigated strains. The clinical strains carried at least one and concomitantly up to as many as eight virulence markers, with two or three being the most common pattern. Most of the strains carried efaA (58.9 %), eep (58.9 %) and esp (57.9 %) genes, whereas the remaining virulence markers were detected in variable percentages ranging from 9.5 to 45 %. Simultaneous presence of virulence markers was observed among clinical strains regardless of their sources. In this study, the efaA + esp + gelE + profile was the virulence genotype most frequently detected among E. faecalis strains. Finally, there was no significant association between virulence markers and clinical sources.


2019 ◽  
Vol 8 (28) ◽  
Author(s):  
Megan M. Mullis ◽  
I-Shuo Huang ◽  
Githzette M. Planas-Costas ◽  
Reavelyn Pray ◽  
Gregory W. Buck ◽  
...  

Vibrio vulnificus is a Gram-negative bacterium and an opportunistic pathogen that can cause septicemia or necrotizing fasciitis. Here, we report the draft genome sequences of 42 environmental V. vulnificus strains collected from the northern Gulf of Mexico. These data will allow for more robust comparisons between clinical and environmental strains.


2008 ◽  
Vol 190 (21) ◽  
pp. 7043-7051 ◽  
Author(s):  
John M. Farrow ◽  
Zoe M. Sund ◽  
Matthew L. Ellison ◽  
Dana S. Wade ◽  
James P. Coleman ◽  
...  

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute and chronic infections in immunocompromised individuals. This gram-negative bacterium produces a battery of virulence factors that allow it to infect and survive in many different hostile environments. The control of many of these virulence factors falls under the influence of one of three P. aeruginosa cell-to-cell signaling systems. The focus of this study, the quinolone signaling system, functions through the Pseudomonas quinolone signal (PQS), previously identified as 2-heptyl-3-hydroxy-4-quinolone. This signal binds to and activates the LysR-type transcriptional regulator PqsR (also known as MvfR), which in turn induces the expression of the pqsABCDE operon. The first four genes of this operon are required for PQS synthesis, but the fifth gene, pqsE, is not. The function of the pqsE gene is not known, but it is required for the production of multiple PQS-controlled virulence factors and for virulence in multiple models of infection. In this report, we show that PqsE can activate PQS-controlled genes in the absence of PqsR and PQS. Our data also suggest that the regulatory activity of PqsE requires RhlR and indicate that a pqsE mutant can be complemented for pyocyanin production by a large excess of exogenous N-butyryl homoserine lactone (C4-HSL). Finally, we show that PqsE enhances the ability of Escherichia coli expressing RhlR to respond to C4-HSL. Overall, our data lead us to conclude that PqsE functions as a regulator that is independent of PqsR and PQS but dependent on the rhl quorum-sensing system.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shaun P. Stice ◽  
Gi Yoon Shin ◽  
Stefanie De Armas ◽  
Santosh Koirala ◽  
Guillermo A. Galván ◽  
...  

Pantoea ananatis is a gram-negative bacterium and the primary causal agent of center rot of onions in Georgia. Previous genomic studies identified two virulence gene clusters, HiVir and alt, associated with center rot. The HiVir gene cluster is required to induce necrosis on onion tissues via synthesis of pantaphos, (2-hydroxy[phosphono-methyl)maleate), a phosphonate phytotoxin. The alt gene cluster aids in tolerance to thiosulfinates generated during onion tissue damage. Whole genome sequencing of other Pantoea species suggests that these gene clusters are present outside of P. ananatis. To assess the distribution of these gene clusters, two PCR primer sets were designed to detect the presence of HiVir and alt. Two hundred fifty-two strains of Pantoea spp. were phenotyped using the red onion scale necrosis (RSN) assay and were genotyped using PCR for the presence of these virulence genes. A diverse panel of strains from three distinct culture collections comprised of 24 Pantoea species, 41 isolation sources, and 23 countries, collected from 1946–2019, was tested. There is a significant association between the alt PCR assay and Pantoea strains recovered from symptomatic onion (P < 0.001). There is also a significant association of a positive HiVir PCR and RSN assay among P. ananatis strains but not among Pantoea spp., congeners. This may indicate a divergent HiVir cluster or different pathogenicity and virulence mechanisms. Last, we describe natural alt positive [RSN+/HiVir+/alt+] P. ananatis strains, which cause extensive bulb necrosis in a neck-to-bulb infection assay compared to alt negative [RSN+/HiVir+/alt–] P. ananatis strains. A combination of assays that include PCR of virulence genes [HiVir and alt] and an RSN assay can potentially aid in identification of onion-bulb-rotting pathogenic P. ananatis strains.


2020 ◽  
Vol 11 ◽  
Author(s):  
Lei Wei ◽  
Qingping Wu ◽  
Jumei Zhang ◽  
Weipeng Guo ◽  
Qihui Gu ◽  
...  

Pseudomonas aeruginosa is an important opportunistic pathogen and remains a major threat to the microbial safety of drinking water. There is a lack of comprehensive data on P. aeruginosa contamination in drinking water in China. Therefore, this study aimed to determine the prevalence, genetic diversity, virulence genes, and antimicrobial resistance of P. aeruginosa isolated from mineral water and spring water in China. From January 2013 to January 2014, 314 drinking water samples were collected from 23 cities in China. Of the collected samples, 77 (24.5%) were contaminated with P. aeruginosa, and these comprised 34 raw water (30.4%), 39 activated carbon-filtered water (30.6%), and four final water product (3.9%). A total of 132 P. aeruginosa isolates were obtained, and all of them showed the presence of virulence genes, with the detection rates of ExoU, ExoS, phzM, toxA, and lasB genes being 7.6, 86.3, 95.5, 89.4, and 100%, respectively. All isolates were sensitive to the 14 antibiotics (ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, gentamicin, tobramycin, amikacin, polymyxin B, imipenem, meropenem, aztreonam, ceftazidime, cefepime, and piperacillin/tazobactam) tested. The 132 isolates were categorized into 42 sequence types according to multilocus sequence typing, and ST235 accounted for 8.3% (11) of the total isolates. Thus, this study provides comprehensive data on the prevalence and characteristics of P. aeruginosa in drinking water in China and can aid in developing preventive measures against contamination during the drinking water treatment process.


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