scholarly journals Hfq, a Novel Pleiotropic Regulator of Virulence-Associated Genes in Francisella tularensis

2009 ◽  
Vol 77 (5) ◽  
pp. 1866-1880 ◽  
Author(s):  
Karin L. Meibom ◽  
Anna-Lena Forslund ◽  
Kerstin Kuoppa ◽  
Khaled Alkhuder ◽  
Iharilalao Dubail ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Tolerance ◽  
Francisella Tularensis ◽  
Rna Binding ◽  
Virulence Gene ◽  
The Other ◽  
Virulence Gene Expression ◽  
Expression Of Genes ◽  
Cellular Stresses ◽  
Pleiotropic Regulator

ABSTRACT Francisella tularensis is a highly infectious pathogen that infects animals and humans, causing tularemia. The ability to replicate within macrophages is central for virulence and relies on expression of genes located in the Francisella pathogenicity island (FPI), as well as expression of other genes. Regulation of FPI-encoded virulence gene expression in F. tularensis involves at least four regulatory proteins and is not fully understood. Here we studied the RNA-binding protein Hfq in F. tularensis and particularly the role that it plays as a global regulator of gene expression in stress tolerance and pathogenesis. We demonstrate that Hfq promotes resistance to several cellular stresses (including osmotic and membrane stresses). Furthermore, we show that Hfq is important for the ability of the F. tularensis vaccine strain LVS to induce disease and persist in organs of infected mice. We also demonstrate that Hfq is important for stress tolerance and full virulence in a virulent clinical isolate of F. tularensis, FSC200. Finally, microarray analyses revealed that Hfq regulates expression of numerous genes, including genes located in the FPI. Strikingly, Hfq negatively regulates only one of two divergently expressed putative operons in the FPI, in contrast to the other known regulators, which regulate the entire FPI. Hfq thus appears to be a new pleiotropic regulator of virulence in F. tularensis, acting mostly as a repressor, in contrast to the other regulators identified so far. Moreover, the results obtained suggest a novel regulatory mechanism for a subset of FPI genes.

scholarly journals Small Molecule Control of Virulence Gene Expression in Francisella tularensis

2009 ◽  
Vol 5 (10) ◽  
pp. e1000641 ◽  
Author(s):  
James C. Charity ◽  
LeeAnn T. Blalock ◽  
Michelle M. Costante-Hamm ◽  
Dennis L. Kasper ◽  
Simon L. Dove
Keyword(s):  
Gene Expression ◽  
Francisella Tularensis ◽  
Small Molecule ◽  
Virulence Gene ◽  
Virulence Gene Expression

scholarly journals The Fatty Acid Regulator FadR Influences the Expression of the Virulence Cascade in the El Tor Biotype of Vibrio cholerae by Modulating the Levels of ToxT via Two Different Mechanisms

2017 ◽  
Vol 199 (7) ◽  
Author(s):  
Gabriela Kovacikova ◽  
Wei Lin ◽  
Ronald K. Taylor ◽  
Karen Skorupski
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Virulence Gene ◽  
Enteric Bacteria ◽  
Posttranslational Regulation ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Expression Of Genes ◽  
El Tor ◽  
Virulence Regulator

ABSTRACT FadR is a master regulator of fatty acid (FA) metabolism that coordinates the pathways of FA degradation and biosynthesis in enteric bacteria. We show here that a ΔfadR mutation in the El Tor biotype of Vibrio cholerae prevents the expression of the virulence cascade by influencing both the transcription and the posttranslational regulation of the master virulence regulator ToxT. FadR is a transcriptional regulator that represses the expression of genes involved in FA degradation, activates the expression of genes involved in unsaturated FA (UFA) biosynthesis, and also activates the expression of two operons involved in saturated FA (SFA) biosynthesis. Since FadR does not bind directly to the toxT promoter, we determined whether the regulation of any of its target genes indirectly influenced ToxT. This was accomplished by individually inserting a double point mutation into the FadR-binding site in the promoter of each target gene, thereby preventing their activation or repression. Although preventing FadR-mediated activation of fabA, which encodes the enzyme that carries out the first step in UFA biosynthesis, did not significantly influence either the transcription or the translation of ToxT, it reduced its levels and prevented virulence gene expression. In the mutant strain unable to carry out FadR-mediated activation of fabA, expressing fabA ectopically restored the levels of ToxT and virulence gene expression. Taken together, the results presented here indicate that V. cholerae FadR influences the virulence cascade in the El Tor biotype by modulating the levels of ToxT via two different mechanisms. IMPORTANCE Fatty acids (FAs) play important roles in membrane lipid homeostasis and energy metabolism in all organisms. In Vibrio cholerae, the causative agent of the acute intestinal disease cholera, they also influence virulence by binding into an N-terminal pocket of the master virulence regulator, ToxT, and modulating its activity. FadR is a transcription factor that coordinately controls the pathways of FA degradation and biosynthesis in enteric bacteria. This study identifies a new link between FA metabolism and virulence in the El Tor biotype by showing that FadR influences both the transcription and posttranslational regulation of the master virulence regulator ToxT by two distinct mechanisms.

scholarly journals Identification of fevR, a Novel Regulator of Virulence Gene Expression in Francisella novicida

2008 ◽  
Vol 76 (8) ◽  
pp. 3473-3480 ◽  
Author(s):  
Anna Brotcke ◽  
Denise M. Monack
Keyword(s):  
Gene Expression ◽  
Regulatory Gene ◽  
Constitutive Expression ◽  
Virulence Gene ◽  
Virulence Gene Expression ◽  
Francisella Novicida ◽  
Expression Of Genes ◽  
Bacterial Replication ◽  
Virulence Gene Regulation

ABSTRACT Francisella tularensis infects wild animals and humans to cause tularemia. This pathogen targets the cytosol of macrophages, where it replicates using the genes in the Francisella pathogenicity island (FPI). Virulence gene regulation in Francisella is complex, but transcriptional regulators MglA and SspA have been shown to regulate the expression of approximately 100 genes, including the entire FPI. We utilized a Francisella novicida transposon mutant library to identify additional regulatory factors and identified five additional genes that are essential for virulence gene expression. One regulatory gene, FTN_0480 (fevR, Francisella effector of virulence regulation), present in all Francisella species, is required for expression of the FPI genes and other genes in the MglA/SspA regulon. The expression of fevR is positively regulated by MglA. However, constitutive expression of fevR in an mglA mutant strain did not restore expression of the MglA/SspA regulon, demonstrating that mglA and fevR act in parallel to positively regulate virulence gene expression. Virulence studies revealed that fevR is essential for bacterial replication in macrophages and in mice, where we additionally show that fevR is required for the expression of genes in the MglA/SspA regulon in vivo. Thus, fevR is a crucial virulence gene in Francisella, required for the expression of virulence factors known to be essential for this pathogen's subversion of host defenses and pathogenesis in vivo.

scholarly journals Twin RNA Polymerase–Associated Proteins Control Virulence Gene Expression in Francisella tularensis

2007 ◽  
Vol 3 (6) ◽  
pp. e84 ◽  
Author(s):  
James C Charity ◽  
Michelle M Costante-Hamm ◽  
Emmy L Balon ◽  
Dana H Boyd ◽  
Eric J Rubin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Francisella Tularensis ◽  
Virulence Gene ◽  
Virulence Gene Expression ◽  
Associated Proteins

Evaluation of antimicrobial effects of photo-sonodynamic antimicrobial chemotherapy based on nano-micelle curcumin on virulence gene expression patterns in Acinetobacter baumannii

2021 ◽  
Vol 22 ◽  
Author(s):  
Maryam Pourhajibagher ◽  
Narjes Talaei ◽  
Abbas Bahador
Keyword(s):  
Gene Expression ◽  
Antimicrobial Chemotherapy ◽  
Irradiation Time ◽  
Expression Patterns ◽  
Virulence Gene ◽  
Blue Laser ◽  
Gene Expression Patterns ◽  
Virulence Gene Expression ◽  
Expression Of Genes ◽  
Ultrasound Power

Background: Abaumannii baumannii rapidly resistance to a wide range of antimicrobial agents. The combination of antimicrobial photodynamic therapy (aPDT) and sonodynamic antimicrobial chemotherapy (SACT) known as photo-sonodynamic antimicrobial chemotherapy (PSACT) has received considerable attention as one of the emerging and promising strategies against microbial infections. Objective: This study aimed to investigate the antimicrobial effects of PSACT based on nano-micelle curcumin (N-MCur) on the virulence gene expression patterns in A. baumannii. Materials and methods: N-MCur as a photo-sonosensitizer was synthesized and confirmed. To determine sub-significant reduction dose of PSACT, sub-significant reduction dose of N-MCur and blue laser light during aPDT, and ultrasound power output during SACT were assessed. Finally, changes in the expression of genes involved in treated A. baumannii by minimum sub-significant reduction dose of PSACT were determined using quantitative real-time-PCR (qRT-PCR). Results: PSACT using 12.5 mM N-MCur at the ultrasound power outputs of 28.7, 36.9, and 45.2 mW/cm2 with 4 min irradiation time of blue laser, as well as, 6.2 mM N-MCur at an ultrasound power output of 45.2 mW/cm2 plus 3 min blue laser irradiation time exhibited the significant dose-dependent reduction against A. baumannii cell viability compared to the control group (P<0.05). After treatment of A. baumannii using 3.1 mM N-MCur + 2 min blue laser irradiation time + 28.7 mW/cm2 ultrasound as the minimum sub-significant reduction doses of PSACT, mRNA expression was significantly upregulated to 6.0-, 11.2-, and 13.7-folds in recA, blsA, and dnaK and downregulated to 8.6-, 10.1-, and 14.5-folds in csuE, espA, and abaI, respectively. Conclusions: N-MCur-mediated PSACT could regulate the expression of genes involved in A. baumannii pathogenesis. Therefore, PSACT can be proposed as a promising application to treat infections caused by A. baumannii.

Vibrio harveyi virulence gene expression in vitro and in vivo during infection in black tiger shrimp Penaeus monodon

2020 ◽  
Vol 139 ◽  
pp. 153-160
Author(s):  
S Peeralil ◽  
TC Joseph ◽  
V Murugadas ◽  
PG Akhilnath ◽  
VN Sreejith ◽  
...  
Keyword(s):  
Gene Expression ◽  
Virulence Genes ◽  
Vibrio Harveyi ◽  
Penaeus Monodon ◽  
Challenge Test ◽  
Virulence Gene ◽  
Economic Losses ◽  
Virulence Gene Expression

Luminescent Vibrio harveyi is common in sea and estuarine waters. It produces several virulence factors and negatively affects larval penaeid shrimp in hatcheries, resulting in severe economic losses to shrimp aquaculture. Although V. harveyi is an important pathogen of shrimp, its pathogenicity mechanisms have yet to be completely elucidated. In the present study, isolates of V. harveyi were isolated and characterized from diseased Penaeus monodon postlarvae from hatcheries in Kerala, India, from September to December 2016. All 23 tested isolates were positive for lipase, phospholipase, caseinase, gelatinase and chitinase activity, and 3 of the isolates (MFB32, MFB71 and MFB68) showed potential for significant biofilm formation. Based on the presence of virulence genes, the isolates of V. harveyi were grouped into 6 genotypes, predominated by vhpA+ flaB+ ser+ vhh1- luxR+ vopD- vcrD+ vscN-. One isolate from each genotype was randomly selected for in vivo virulence experiments, and the LD50 ranged from 1.7 ± 0.5 × 103 to 4.1 ± 0.1 × 105 CFU ml-1. The expression of genes during the infection in postlarvae was high in 2 of the isolates (MFB12 and MFB32), consistent with the result of the challenge test. However, in MFB19, even though all genes tested were present, their expression level was very low and likely contributed to its lack of virulence. Because of the significant variation in gene expression, the presence of virulence genes alone cannot be used as a marker for pathogenicity of V. harveyi.

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