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.

scholarly journals Pneumococcal Virulence Gene Expression and Host Cytokine Profiles during Pathogenesis of Invasive Disease

2007 ◽  
Vol 76 (2) ◽  
pp. 646-657 ◽  
Author(s):  
Layla K. Mahdi ◽  
Abiodun D. Ogunniyi ◽  
Kim S. LeMessurier ◽  
James C. Paton
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Virulence Gene ◽  
Invasive Disease ◽  
Gene Expression Patterns ◽  
Putative Virulence Factor ◽  
Necrosis Factor Alpha ◽  
Virulence Gene Expression

ABSTRACTPneumococcal disease continues to account for significant morbidity and mortality worldwide. For the development of novel prophylactic and therapeutic strategies against the disease spectrum, a complete understanding of pneumococcal behavior in vivo is necessary. We evaluated the expression patterns of the proven and putative virulence factor genesadcR,cbpA,cbpD,cbpG,cpsA,nanA,pcpA,piaA,ply,psaA,pspA, andspxBafter intranasal infection of CD1 mice with serotype 2, 4, and 6A pneumococci by real-time reverse transcription-PCR. Simultaneous gene expression patterns of selected host immunomodulatory molecules, CCL2, CCL5, CD54, CXCL2, interleukin-6, and tomor necrosis factor alpha, were also investigated. We show that pneumococcal virulence genes are differentially expressed in vivo, with some genes demonstrating niche- and serotype-specific differential expression. The in vivo expression patterns could not be attributed to in vitro differences in expression of the genes in transparent and opaque variants of the three strains. The host molecules were significantly upregulated, especially in the lungs, blood, and brains of mice. The pneumococcal-gene expression patterns support their ascribed roles in pathogenesis, providing insight into which protein combinations might be more appropriate as vaccine antigens against invasive disease. This is the first simultaneous comparison of bacterial- and host gene expression in the same animal during pathogenesis. The strategy provides a platform for prospective evaluation of interaction kinetics between invading pneumococci and human patients in culture-positive cases and should be feasible in other infection models.

scholarly journals Evaluation of Virulence Gene Expression Patterns inAcinetobacter baumanniiUsing Quantitative Real-Time Polymerase Chain Reaction Array

2016 ◽  
Vol 181 (9) ◽  
pp. 1108-1113 ◽  
Author(s):  
Ford M. Lannan ◽  
Daniel K. O'conor ◽  
Joseph C. Broderick ◽  
Jamison F. Tate ◽  
Jacob T. Scoggin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polymerase Chain Reaction ◽  
Real Time ◽  
Expression Patterns ◽  
Virulence Gene ◽  
Gene Expression Patterns ◽  
Chain Reaction ◽  
Virulence Gene Expression ◽  
Polymerase Chain

scholarly journals Molecular Characteristics of Streptococcus pyogenes Isolated From Chinese Children With Different Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Dingle Yu ◽  
Yunmei Liang ◽  
Qinghua Lu ◽  
Qing Meng ◽  
Wenjian Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Antibiotic Resistance ◽  
Streptococcus Pyogenes ◽  
Wide Spectrum ◽  
Expression Patterns ◽  
Virulence Gene ◽  
High Rate ◽  
Molecular Characteristics ◽  
Virulence Gene Expression ◽  
Obstructive Sleep

Streptococcus pyogenes is a bacterial pathogen that causes a wide spectrum of clinical diseases exclusively in humans. The distribution of emm type, antibiotic resistance and virulence gene expression for S. pyogenes varies temporally and geographically, resulting in distinct disease spectra. In this study, we analyzed antibiotic resistance and resistance gene expression patterns among S. pyogenes isolates from pediatric patients in China and investigated the relationship between virulence gene expression, emm type, and disease categories. Forty-two representative emm1.0 and emm12.0 strains (n = 20 and n = 22, respectively) isolated from patients with scarlet fever or obstructive sleep apnea-hypopnea syndrome were subjected to whole-genome sequencing and phylogenetic analysis. These strains were further analyzed for susceptibility to vancomycin. We found a high rate and degree of resistance to macrolides and tetracycline in these strains, which mainly expressed ermB and tetM. The disease category correlated with emm type but not superantigens. The distribution of vanuG and virulence genes were associated with emm type. Previously reported important prophages, such as φHKU16.vir, φHKU488.vir, Φ5005.1, Φ5005.2, and Φ5005.3 encoding streptococcal toxin, and integrative conjugative elements (ICEs) such as ICE-emm12 and ICE-HKU397 encoding macrolide and tetracycline resistance were found present amongst emm1 or emm12 clones from Shenzhen, China.

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 DNA Adenine Methylation Regulates Virulence Gene Expression in Salmonella enterica Serovar Typhimurium

2006 ◽  
Vol 188 (23) ◽  
pp. 8160-8168 ◽  
Author(s):  
Roberto Balbontín ◽  
Gary Rowley ◽  
M. Graciela Pucciarelli ◽  
Javier López-Garrido ◽  
Yvette Wormstone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Salmonella Enterica ◽  
Expression Patterns ◽  
Virulence Gene ◽  
Luria Bertani ◽  
Altered Expression ◽  
Virulence Gene Expression ◽  
Adenine Methylation ◽  
Dam Methylation ◽  
Serovar Typhimurium

ABSTRACT Transcriptomic analyses during growth in Luria-Bertani medium were performed in strain SL1344 of Salmonella enterica serovar Typhimurium and in two isogenic derivatives lacking Dam methylase. More genes were repressed than were activated by Dam methylation (139 versus 37). Key genes that were differentially regulated by Dam methylation were verified independently. The largest classes of Dam-repressed genes included genes belonging to the SOS regulon, as previously described in Escherichia coli, and genes of the SOS-inducible Salmonella prophages ST64B, Gifsy-1, and Fels-2. Dam-dependent virulence-related genes were also identified. Invasion genes in pathogenicity island SPI-1 were activated by Dam methylation, while the fimbrial operon std was repressed by Dam methylation. Certain flagellar genes were repressed by Dam methylation, and Dam− mutants of S. enterica showed reduced motility. Altered expression patterns in the absence of Dam methylation were also found for the chemotaxis genes cheR (repressed by Dam) and STM3216 (activated by Dam) and for the Braun lipoprotein gene, lppB (activated by Dam). The requirement for DNA adenine methylation in the regulation of specific virulence genes suggests that certain defects of Salmonella Dam− mutants in the mouse model may be caused by altered patterns of gene expression.

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 Antistress Action of Melanocortin Derivatives Associated with Correction of Gene Expression Patterns in the Hippocampus of Male Rats Following Acute Stress

2021 ◽  
Vol 22 (18) ◽  
pp. 10054
Author(s):  
Ivan B. Filippenkov ◽  
Vasily V. Stavchansky ◽  
Natalya Yu. Glazova ◽  
Elena A. Sebentsova ◽  
Julia A. Remizova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Stress ◽  
Expression Patterns ◽  
Molecular Genetic ◽  
Male Rats ◽  
Gene Expression Patterns ◽  
P Value ◽  
Behavioral Alterations ◽  
Expression Levels ◽  
Expression Of Genes

Natural melanocortins (MCs) have been used in the successful development of drugs with neuroprotective properties. Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4–7)PGP (Semax) and ACTH(6–9)PGP under normal and acute restraint stress (ARS) conditions. Administration of Semax or ACTH(6–9)PGP (100 μg/kg) to rats 30 min before ARS attenuated ARS-induced behavioral alterations. Using high-throughput RNA sequencing (RNA-Seq), we identified 1359 differentially expressed genes (DEGs) in the hippocampus of vehicle-treated rats subjected to ARS, using a cutoff of >1.5 fold change and adjusted p-value (Padj) < 0.05, in samples collected 4.5 h after the ARS. Semax administration produced >1500 DEGs, whereas ACTH(6–9)PGP administration led to <400 DEGs at 4.5 h after ARS. Nevertheless, ~250 overlapping DEGs were identified, and expression of these DEGs was changed unidirectionally by both peptides under ARS conditions. Modulation of the expression of genes associated with biogenesis, translation of RNA, DNA replication, and immune and nervous system function was produced by both peptides. Furthermore, both peptides upregulated the expression levels of many genes that displayed decreased expression after ARS, and vice versa, the MC peptides downregulated the expression levels of genes that were upregulated by ARS. Consequently, the antistress action of MC peptides may be associated with a correction of gene expression patterns that are disrupted during ARS.

Differential Expression of Genes Associated with Toll-Like Receptor-4 (TLR4) Signal Transduction Pathway in Lipopolysaccharide (LPS)-Activated Cord Blood (CB) vs. Adult Peripheral Blood (APB) Monocyte (Mo)-Derived Dendritic Cells (DC).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3444-3444
Author(s):  
Hong Jiang ◽  
Mary Brigid Bradley ◽  
Carmella van de Ven ◽  
Prakash Satwani ◽  
Laxmi Baxi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Protein Expression ◽  
Expression Patterns ◽  
Signal Transduction Pathway ◽  
Gene Expression Patterns ◽  
Transduction Pathway ◽  
Rt Pcr ◽  
Cell Surface Molecule ◽  
Expression Of Genes

Abstract LPS activates immature DC via TLR4 and induces maturation of DC for initiating antigen presenting activity (Medzhitov; Nat Rev Immunol 2001). We have previously demonstrated decreased gene expression and protein production of IL-12, IL-15, IL-18 in activated CB MNC and decreased DC MLR (Lee/Cairo, Blood 1996; Qian/Cairo, Blood 1997; Wu/Cairo, Blood 100:3668 p51b 2002). Recently, we have identified differential gene expression patterns including differential immunoregulatory and chemokine genes in LPS-CB vs APB Mo by microarray (Jiang/Cairo, J. Immunol 2004). Since the myeloid lineage DC is derived from Mo, we sought to determine in LPS activated CB vs. APB DC, differential expressed genes that associate with TLR4-mediated signaling pathway. Briefly, Mo were purified from fresh CB or APB and cultured for 7 days with GM-CSF & IL-4 [immature DC (iDC)] and LPS [mature DC (mDC)]. Aliquots from iDC and mDC were analyzed for DC immunophenotype, morphology and DC allogeneic antigen activity. mRNA was isolated, reverse transcripted to cDNA, labeled & hybridized to oligonucleotides (Affymetrix, U133A). Data was analyzed by MAS 5.0 (Affymetrix) and GeneSpring 5.0 software (Silicon Genetics). Several genes were analyzed by RT-PCR (One-Step SuperScript, Invitrogen) and protein expression was analyzed by Western Blot (Bio-Rad). Inverted microscopy demonstrated DC mature morphology at day 8 and flow cytometry demonstrated decreased CD14 and increased CD83 expression in CB & APB mDC. We also demonstrated significant increase in the allogeneic stimulatory effects on CD4+ T cells in APB vs. CB mDC. The microarray analysis demonstrated a significant decreased gene expression of TLR4 [3 fold (F)] and CD14 (2.1 F) (p<0.05) in CB vs APB-DC. We further identified LPS significantly induced increased expression of TLR4 downstream signaling molecular genes such as MAPKKK, NF-kB and TANK in APB compared to CB mDC (3–8 F) (p<0.05). There were also significant amplifications of a variety of other gene categories in LPS activated APB vs CB mDC (p<0.05) including cell surface molecule CD80 (3.7F) and IL-2Ra (5.3 F), cytokine IL-23 (3.5F) & IL-12 (13 F), signal transduction STAT1 (3.4F) & IRF-7 (7.7 F), and immunoregulatory TNFSF10 (12F) & ISG20 (39F). Gene expression of NF-kB1, TRAF1 & IRF-7 by RT-PCR demonstrated an increased expression in LPS-APB vs CB mDC and were compatible with microarray. Moreover, Western analysis of IRF-7 demonstrated increased protein expression in LPS-APB vs CB mDC. In summary, we have identified decreased gene expression patterns in LPS-CB vs APB DC, especially those in the TLR4 signal transduction pathway (MAP3K, TRAF, TANK & NF-kB), and suggest these differentially expressed genes may enhance the activation of TLR4 pathway in LPS-APB vs CB DC, resulting in differential regulation of CB vs APB DC antigen presentation capacities. Furthermore, these decreased expressed genes in other molecular categories (e.g.IL-23, IFNg, IL6, CD80, STAT1, IRF-7, SOCS3) in LPS-CB vs APB DC may be partially responsible for differential innate and adaptive immune function of CB vs APB. Moreover, the differential regulated expression of genes may in part help to explain reduced incidence of severe aGVHD, delay in immune reconstitution and/or increased infectious mortality following HLA disparate UCBT.

scholarly journals Patterns of gene expression in the sheep heart during the perinatal period revealed by transcriptomic modeling

2015 ◽  
Vol 47 (9) ◽  
pp. 407-419 ◽  
Author(s):  
Elaine M. Richards ◽  
M. Belen Rabaglino ◽  
Andrew Antolic ◽  
Charles E. Wood ◽  
Maureen Keller-Wood
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Expression Patterns ◽  
Perinatal Period ◽  
Gene Expression Patterns ◽  
Acid Oxidation ◽  
Expression Of Genes ◽  
Development And Differentiation ◽  
Near Term ◽  
Coexpressed Genes

Septa from sheep hearts at 130 days gestation, term, and 14-day-old lambs were used to model the changes in gene expression patterns during the perinatal period using Agilent 15k ovine microarrays. We used Bioconductor for R to model five major patterns of coexpressed genes. Gene ontology and transcription factor analyses using Webgestalt modeled the biological significances and transcription factors of the gene expression patterns. Modeling indicated a decreased expression of genes associated with anatomical development and differentiation during this period, whereas those associated with increased protein synthesis and growth associated with maturation of the endoplasmic reticulum rose to term but did not further increase from the near term expression. Expression of genes associated with cell responsiveness, for example, immune responses, decreased at term but expression returned by postnatal day 14. Changes in genes related to metabolism showed differential substrate-associated patterns: those related to carbohydrate metabolism rose to term and remained stable thereafter, whereas those associated with fatty acid oxidation facility rose throughout the period. The timing of many of these maturational processes was earlier in relation to birth than in the rodent. The importance of the transcription factors, estrogen-related receptors, and v-myc avian myelocytomatosis viral oncogene homolog was also highlighted in the pattern of gene expression during development of the perinatal sheep heart.

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