scholarly journals Sodium Selenite Enhances Antibiotics Sensitivity of Pseudomonas aeruginosa and Deceases Its Pathogenicity by Inducing Oxidative Stress and Inhibiting Quorum Sensing System

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1873
Author(s):  
Weina Kong ◽  
Qianqian Tian ◽  
Qiaoli Yang ◽  
Yu Liu ◽  
Gongting Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Sodium Selenite ◽  
Opportunistic Pathogen ◽  
H2o2 Treatment ◽  
Adjunct Treatment ◽  
Sensing System ◽  
Virulence Attenuation ◽  
Quorum Sensing System

Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, is commonly found in clinical settings and immuno-compromised patients. It is difficult to be eradicated due to its strong antibiotic resistance, and novel inactivation strategies have yet to be developed. Selenium is an essential microelement for humans and has been widely used in dietary supplement and chemoprevention therapy. In this study, the physiological and biochemical effects of sodium selenite on P. aeruginosa PAO1 were investigated. The results showed that 0~5 mM sodium selenite did not impact the growth of PAO1, but increased the lethality rate of PAO1 with antibiotics or H2O2 treatment and the antibiotics susceptibility both in planktonic and biofilm states. In addition, sodium selenite significantly reduced the expression of quorum sensing genes and inhibited various virulence factors of this bacterium, including pyocyanin production, bacterial motilities, and the type III secretion system. Further investigation found that the content of ROS in cells was significantly increased and the expression levels of most genes involved in oxidative stress were up-regulated, which indicated that sodium selenite induced oxidative stress. The RNA-seq result confirmed the phenotypes of virulence attenuation and the expression of quorum sensing and antioxidant-related genes. The assays of Chinese cabbage and Drosophila melanogaster infection models showed that the combination of sodium selenite and antibiotics significantly alleviated the infection of PAO1. In summary, the results revealed that sodium selenite induced oxidative stress and inhibited the quorum sensing system of P. aeruginosa, which in turn enhanced the antibiotic susceptibility and decreased the pathogenicity of this bacterium. These findings suggest that sodium selenite may be used as an effective strategy for adjunct treatment of the infections caused by P. aeruginosa.

scholarly journals Pseudomonas aeruginosa Regulatory Protein AnvM Controls Pathogenicity in Anaerobic Environments and Impacts Host Defense

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Yingchao Zhang ◽  
Chuan-min Zhou ◽  
Qinqin Pu ◽  
Qun Wu ◽  
Shirui Tan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Anaerobic Conditions ◽  
Content Type ◽  
Sensing System ◽  
Quorum Sensing System ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

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.

scholarly journals Tobramycin Adaptation Enhances Policing of Social Cheaters in Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Rhea G. Abisado ◽  
John H. Kimbrough ◽  
Brielle M. McKee ◽  
Vaughn D. Craddock ◽  
Nicole E. Smalley ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Opportunistic Pathogen ◽  
Sole Source ◽  
Independent Manner ◽  
Adaptive Mutations ◽  
Sensing System ◽  
Quorum Sensing System ◽  
Secreted Proteases ◽  
Work Supports

The Pseudomonas aeruginosa LasR-I quorum-sensing system regulates secreted proteases that can be exploited by cheaters, such as quorum sensing receptor-defective (lasR) mutants. lasR mutants emerge in populations growing on casein as a sole source of carbon and energy. These mutants are exploitative cheaters because they avoid the substantial cost of engaging in quorum sensing. Previous studies showed that quorum sensing increases resistance to some antibiotics, such as tobramycin. Here, we show that tobramycin suppressed the emergence of lasR mutants in casein-passaged populations. Several mutations accumulated in those populations indicating evidence of antibiotic adaptation. We found that mutations in one gene, ptsP, increased antibiotic resistance and also pleiotropically increased production of a quorum sensing-controlled phenazine, pyocyanin. When passaged on casein, ptsP mutants suppressed cheaters in a manner that was tobramycin independent. We found the mechanism of cheater suppression in ptsP mutants relied on pyocyanin, which acts as a policing toxin by selectively blocking growth of cheaters. Thus, tobramycin suppresses lasR mutants through two mechanisms: first, through direct effects on cheaters and second, by selecting mutations in ptsP that suppressed cheating in a tobramycin-independent manner. This work demonstrates how adaptive mutations can alter the dynamics of cooperator-cheater relationships, which might be important for populations adapting to antibiotics during interspecies competition or infections. IMPORTANCE The opportunistic pathogen Pseudomonas aeruginosa is a model for understanding quorum sensing, a type of cell-cell signaling important for cooperation. Quorum sensing controls production of cooperative goods, such as exoenzymes, which are vulnerable to cheating by quorum sensing-defective mutants. Because uncontrolled cheating can ultimately cause a population to collapse, much focus has been on understanding how P. aeruginosa can control cheaters. We show that an antibiotic, tobramycin, can suppress cheaters in cooperating P. aeruginosa populations. Tobramycin suppresses cheaters directly because the cheaters are more susceptible to tobramycin than cooperators. Tobramycin also selects for mutations in a gene, ptsP, that suppresses cheaters independent of tobramycin through pleiotropic regulation of a policing toxin, pyocyanin. This work supports the idea that adaptation to antibiotics can have unexpected effects on the evolution of quorum sensing and has implications for understanding how cooperation evolves in dynamic bacterial communities.

scholarly journals The Pseudomonas Quinolone Signal Regulates rhl Quorum Sensing in Pseudomonas aeruginosa

2000 ◽  
Vol 182 (10) ◽  
pp. 2702-2708 ◽  
Author(s):  
Susan L. McKnight ◽  
Barbara H. Iglewski ◽  
Everett C. Pesci
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Sensing System ◽  
Sensing Systems ◽  
Pseudomonas Quinolone Signal ◽  
Quorum Sensing System ◽  
Encoding Gene

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.

scholarly journals Regulation of Pseudomonas Quinolone Signal Synthesis in Pseudomonas aeruginosa

2005 ◽  
Vol 187 (13) ◽  
pp. 4372-4380 ◽  
Author(s):  
Dana S. Wade ◽  
M. Worth Calfee ◽  
Edson R. Rocha ◽  
Elizabeth A. Ling ◽  
Elana Engstrom ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Transcriptional Start Site ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Mobility Shift ◽  
Sensing System ◽  
Regulator Protein ◽  
Quorum Sensing System

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung infections in cystic fibrosis patients and is a major source of nosocomial infections. This bacterium controls many virulence factors by using two quorum-sensing systems, las and rhl. The las system is composed of the LasR regulator protein and its cell-to-cell signal, N-(3-oxododecanoyl) homoserine lactone, and the rhl system is composed of RhlR and the signal N-butyryl homoserine lactone. A third intercellular signal, the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4-quinolone), also regulates numerous virulence factors. PQS synthesis requires the expression of multiple operons, one of which is pqsABCDE. Previous experiments showed that the transcription of this operon, and therefore PQS production, is negatively regulated by the rhl quorum-sensing system and positively regulated by the las quorum-sensing system and PqsR (also known as MvfR), a LysR-type transcriptional regulator protein. With the use of DNA mobility shift assays and β-galactosidase reporter fusions, we have studied the regulation of pqsR and its relationship to pqsA, lasR, and rhlR. We show that PqsR binds the promoter of pqsA and that this binding increases dramatically in the presence of PQS, implying that PQS acts as a coinducer for PqsR. We have also mapped the transcriptional start site for pqsR and found that the transcription of pqsR is positively regulated by lasR and negatively regulated by rhlR. These results suggest that a regulatory chain occurs where pqsR is under the control of LasR and RhlR and where PqsR in turn controls pqsABCDE, which is required for the production of PQS.

scholarly journals PqsE Functions Independently of PqsR-Pseudomonas Quinolone Signal and Enhances the rhl Quorum-Sensing System

2008 ◽  
Vol 190 (21) ◽  
pp. 7043-7051 ◽  
Author(s):  
John M. Farrow ◽  
Zoe M. Sund ◽  
Matthew L. Ellison ◽  
Dana S. Wade ◽  
James P. Coleman ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Virulence Factors ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Chronic Infections ◽  
Signaling Systems ◽  
Sensing System ◽  
Pseudomonas Quinolone Signal ◽  
Quorum Sensing System ◽  
Hostile Environments

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.

scholarly journals Mutation of pfm affects the adherence of Pseudomonas aeruginosa to host cells and the quorum sensing system

2011 ◽  
Vol 324 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Rui Mou ◽  
Fang Bai ◽  
Qiaonan Duan ◽  
Xuehan Wang ◽  
Haijin Xu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Host Cells ◽  
Sensing System ◽  
Quorum Sensing System
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