scholarly journals The Pseudomonas aeruginosa Magnesium Transporter MgtE Inhibits Transcription of the Type III Secretion System

2009 ◽  
Vol 78 (3) ◽  
pp. 1239-1249 ◽  
Author(s):  
Gregory G. Anderson ◽  
Timothy L. Yahr ◽  
Rustin R. Lovewell ◽  
George A. O'Toole
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Epithelial Cells ◽  
Type Iii Secretion ◽  
Biofilm Formation ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Bacterial Biofilm ◽  
Magnesium Transport ◽  
Type Iii ◽  
Magnesium Transporter

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes life-long pneumonia in individuals with cystic fibrosis (CF). These long-term infections are maintained by bacterial biofilm formation in the CF lung. We have recently developed a model of P. aeruginosa biofilm formation on cultured CF airway epithelial cells. Using this model, we discovered that mutation of a putative magnesium transporter gene, called mgtE, led to increased cytotoxicity of P. aeruginosa toward epithelial cells. This altered toxicity appeared to be dependent upon expression of the type III secretion system (T3SS). In this study, we found that mutation of mgtE results in increased T3SS gene transcription. Through epistasis analyses, we discovered that MgtE influences the ExsE-ExsC-ExsD-ExsA gene regulatory system of T3SS by either directly or indirectly inhibiting ExsA activity. While variations in calcium levels modulate T3SS gene expression in P. aeruginosa, we found that addition of exogenous magnesium did not inhibit T3SS activity. Furthermore, mgtE variants that were defective for magnesium transport could still complement the cytotoxicity effect. Thus, the magnesium transport function of MgtE does not fully explain the regulatory effects of MgtE on cytotoxicity. Overall, our results indicate that MgtE modulates expression of T3SS genes.

scholarly journals YbeY controls the type III and type VI secretion systems and biofilm formation through RetS in Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Yushan Xia ◽  
Congjuan Xu ◽  
Dan Wang ◽  
Yuding Weng ◽  
Yongxin Jin ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Biofilm Formation ◽  
Small Rnas ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Type Vi Secretion System ◽  
Chronic Infections ◽  
Type Iii ◽  
Type Vi Secretion

YbeY is a highly conserved RNase in bacteria and plays essential roles in the maturation of 16S rRNA, regulation of small RNAs (sRNAs) and bacterial responses to environmental stresses. Previously, we verified the role of YbeY in rRNA processing and ribosome maturation in Pseudomonas aeruginosa and demonstrated YbeY-mediated regulation of rpoS through a sRNA ReaL. In this study, we demonstrate that mutation of the ybeY gene results in upregulation of the type III secretion system (T3SS) genes as well as downregulation of the type VI secretion system (T6SS) genes and reduction of biofilm formation. By examining the expression of the known sRNAs in P. aeruginosa, we found that mutation of the ybeY gene leads to downregulation of the small RNAs RsmY/Z that control the T3SS, the T6SS and biofilm formation. Further studies revealed that the reduced levels of RsmY/Z are due to upregulation of retS. Taken together, our results reveal the pleiotropic functions of YbeY and provide detailed mechanisms of YbeY-mediated regulation in P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa causes a variety of acute and chronic infections in humans. The type III secretion system (T3SS) plays an important role in acute infection and the type VI secretion system (T6SS) and biofilm formation are associated with chronic infections. Understanding of the mechanisms that control the virulence determinants involved in acute and chronic infections will provide clues for the development of effective treatment strategies. Our results reveal a novel RNase mediated regulation on the T3SS, T6SS and biofilm formation in P. aeruginosa.

scholarly journals Pseudomonas aeruginosa Magnesium Transporter MgtE Inhibits Type III Secretion System Gene Expression by Stimulating rsmYZ Transcription

2017 ◽  
Vol 199 (23) ◽  
Author(s):  
Shubham Chakravarty ◽  
Cameron N. Melton ◽  
Adam Bailin ◽  
Timothy L. Yahr ◽  
Gregory G. Anderson
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Gene Transcription ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Host Cells ◽  
Content Type ◽  
Type Iii ◽  
Magnesium Transporter

ABSTRACT Pseudomonas aeruginosa causes numerous acute and chronic opportunistic infections in humans. One of its most formidable weapons is a type III secretion system (T3SS), which injects powerful toxins directly into host cells. The toxins lead to cell dysfunction and, ultimately, cell death. Identification of regulatory pathways that control T3SS gene expression may lead to the discovery of novel therapeutics to treat P. aeruginosa infections. In a previous study, we found that expression of the magnesium transporter gene mgtE inhibits T3SS gene transcription. MgtE-dependent inhibition appeared to interfere with the synthesis or function of the master T3SS transcriptional activator ExsA, although the exact mechanism was unclear. We now demonstrate that mgtE expression acts through the GacAS two-component system to activate rsmY and rsmZ transcription. This event ultimately leads to inhibition of exsA translation. This inhibitory effect is specific to exsA as translation of other genes in the exsCEBA operon is not inhibited by mgtE. Moreover, our data reveal that MgtE acts solely through this pathway to regulate T3SS gene transcription. Our study reveals an important mechanism that may allow P. aeruginosa to fine-tune T3SS activity in response to certain environmental stimuli. IMPORTANCE The type III secretion system (T3SS) is a critical virulence factor utilized by numerous Gram-negative bacteria, including Pseudomonas aeruginosa, to intoxicate and kill host cells. Elucidating T3SS regulatory mechanisms may uncover targets for novel anti-P. aeruginosa therapeutics and provide deeper understanding of bacterial pathogenesis. We previously found that the magnesium transporter MgtE inhibits T3SS gene transcription in P. aeruginosa. In this study, we describe the mechanism of MgtE-dependent inhibition of the T3SS. Our report also illustrates how MgtE might respond to environmental cues, such as magnesium levels, to fine-tune T3SS gene expression.

scholarly journals The Posttranscriptional Regulator RsmA Plays a Role in the Interaction between Pseudomonas aeruginosa and Human Airway Epithelial Cells by Positively Regulating the Type III Secretion System

2006 ◽  
Vol 74 (5) ◽  
pp. 3012-3015 ◽  
Author(s):  
Heidi Mulcahy ◽  
Julie O'Callaghan ◽  
Eoin P. O'Grady ◽  
Claire Adams ◽  
Fergal O'Gara
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Epithelial Cells ◽  
Type Iii Secretion ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Type Iii Secretion System ◽  
Airway Epithelial Cells ◽  
Secretion System ◽  
Airway Epithelial ◽  
Type Iii

ABSTRACT Posttranscriptional regulation of certain virulence-related genes in Pseudomonas aeruginosa is brought about by RsmA, a small RNA-binding protein. During interaction with airway epithelial cells, RsmA promoted actin depolymerization, cytotoxicity, and anti-internalization of P. aeruginosa by positively regulating the virulence-associated type III secretion system.

scholarly journals Macrophages and Epithelial Cells Respond Differently to the Pseudomonas aeruginosa Type III Secretion System

1999 ◽  
Vol 67 (6) ◽  
pp. 3151-3154 ◽  
Author(s):  
Jenifer Coburn ◽  
Dara W. Frank
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Epithelial Cells ◽  
Target Cell ◽  
Type Iii Secretion ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Lung Epithelial Cells ◽  
Cell Type ◽  
Type Iii ◽  
Lung Epithelial

ABSTRACT The multiple effects of Pseudomonas aeruginosa type III secretion have largely been attributed to variations in cytotoxin expression between strains. Here we show that the target cell type is also important. While lung epithelial cells showed significant changes in morphology but not viability when infected with P. aeruginosa, macrophages were efficiently killed by P. aeruginosa. Both responses were dependent on the type III secretion system.

scholarly journals HigB Reciprocally Controls Biofilm Formation and the Expression of Type III Secretion System Genes through Influencing the Intracellular c-di-GMP Level in Pseudomonas aeruginosa

Toxins ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 424 ◽  
Author(s):  
Yueying Zhang ◽  
Bin Xia ◽  
Mei Li ◽  
Jing Shi ◽  
Yuqing Long ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Type Iii Secretion ◽  
Biofilm Formation ◽  
Pathogenic Bacteria ◽  
Regulatory Mechanism ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Regulatory Pathways ◽  
Type Iii

Toxin-antitoxin (TA) systems play important roles in bacteria persister formation. Increasing evidence demonstrate the roles of TA systems in regulating virulence factors in pathogenic bacteria. The toxin HigB in Pseudomonas aeruginosa contributes to persister formation and regulates the expression of multiple virulence factors and biofilm formation. However, the regulatory mechanism remains elusive. In this study, we explored the HigB mediated regulatory pathways. We demonstrate that HigB decreases the intracellular level of c-di-GMP, which is responsible for the increased expression of the type III secretion system (T3SS) genes and repression of biofilm formation. By analyzing the expression levels of the known c-di-GMP metabolism genes, we find that three c-di-GMP hydrolysis genes are up regulated by HigB, namely PA2133, PA2200 and PA3825. Deletion of the three genes individually or simultaneously diminishes the HigB mediated regulation on the expression of T3SS genes and biofilm formation. Therefore, our results reveal novel functions of HigB in P. aeruginosa.

scholarly journals Positive regulation of Type III secretion effectors and virulence by RyhB paralogs in Salmonella enterica serovar Enteritidis

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Binjie Chen ◽  
Xianchen Meng ◽  
Jie Ni ◽  
Mengping He ◽  
Yanfei Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Intestinal Epithelial Cells ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Intestinal Epithelial ◽  
Type Iii ◽  
Effector Gene ◽  
T3ss Effector

AbstractSmall non-coding RNA RyhB is a key regulator of iron homeostasis in bacteria by sensing iron availability in the environment. Although RyhB is known to influence bacterial virulence by interacting with iron metabolism related regulators, its interaction with virulence genes, especially the Type III secretion system (T3SS), has not been reported. Here, we demonstrate that two RyhB paralogs of Salmonella enterica serovar Enteritidis upregulate Type III secretion system (T3SS) effectors, and consequently affect Salmonella invasion into intestinal epithelial cells. Specifically, we found that RyhB-1 modulate Salmonella response to stress condition of iron deficiency and hypoxia, and stress in simulated intestinal environment (SIE). Under SIE culture conditions, both RyhB-1 and RyhB-2 are drastically induced and directly upregulate the expression of T3SS effector gene sipA by interacting with its 5′ untranslated region (5′ UTR) via an incomplete base-pairing mechanism. In addition, the RyhB paralogs upregulate the expression of T3SS effector gene sopE. By regulating the invasion-related genes, RyhBs in turn affect the ability of S. Enteritidis to adhere to and invade into intestinal epithelial cells. Our findings provide evidence that RyhBs function as critical virulence factors by directly regulating virulence-related gene expression. Thus, inhibition of RyhBs may be a potential strategy to attenuate Salmonella.

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