scholarly journals Phenobarbital Induction and Chemical Synergism Demonstrate the Role of UDP-Glucuronosyltransferases in Detoxification of Naphthalophos by Haemonchus contortus Larvae

2014 ◽  
Vol 58 (12) ◽  
pp. 7475-7483 ◽  
Author(s):  
Andrew C. Kotze ◽  
Angela P. Ruffell ◽  
Aaron B. Ingham
Keyword(s):  
Haemonchus Contortus ◽  
Synergistic Effects ◽  
Cytochromes P450 ◽  
Resistance Mechanism ◽  
Fold Increase ◽  
Protective Role ◽  
Detoxification Enzymes ◽  
Content Type ◽  
Parasitic Worms

ABSTRACTWe used an enzyme induction approach to study the role of detoxification enzymes in the interaction of the anthelmintic compound naphthalophos withHaemonchus contortuslarvae. Larvae were treated with the barbiturate phenobarbital, which is known to induce the activity of a number of detoxification enzymes in mammals and insects, including cytochromes P450 (CYPs), UDP-glucuronosyltransferases (UDPGTs), and glutathione (GSH)S-transferases (GSTs). Cotreatment of larvae with phenobarbital and naphthalophos resulted in a significant increase in the naphthalophos 50% inhibitory concentration (IC50) compared to treatment of larvae with the anthelmintic alone (up to a 28-fold increase). The phenobarbital-induced drug tolerance was reversed by cotreatment with the UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, probenecid, and sulfinpyrazone. Isobologram analysis of the interaction of 5-nitrouracil with naphthalophos in phenobarbital-treated larvae clearly showed the presence of strong synergism. The UDPGT inhibitors 5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine, and probenecid also showed synergistic effects with non-phenobarbital-treated worms (synergism ratio up to 3.2-fold). This study indicates thatH. contortuslarvae possess one or more UDPGT enzymes able to detoxify naphthalophos. In highlighting the protective role of this enzyme group, this study reveals the potential for UDPGT enzymes to act as a resistance mechanism that may develop under drug selection pressure in field isolates of this species. In addition, the data indicate the potential for a chemotherapeutic approach utilizing inhibitors of UDPGT enzymes as synergists to increase the activity of naphthalophos against parasitic worms and to combat detoxification-mediated drug resistance if it arises in the field.

Learning organization and organizational citizenship behaviour in West Malaysia: moderating role of team-oriented culture

2020 ◽  
Vol 44 (8/9) ◽  
pp. 847-864
Author(s):  
Patricia Yin Yin Lau ◽  
Sunyoung Park ◽  
Gary N. McLean
Keyword(s):  
Learning Organization ◽  
Organizational Citizenship ◽  
Organizational Citizenship Behavior ◽  
Synergistic Effects ◽  
Citizenship Behavior ◽  
Content Type ◽  
High Power Distance ◽  
The Relationship ◽  
Moderating Role

Purpose This study aims to examine the relationship between having a learning organization (LO) and organizational citizenship behavior (OCB), and the moderating role of team-oriented culture on this relationship. Design/methodology/approach Using 516 respondents from diverse industries in West Malaysia, the authors tested the psychometric properties of the three variables. Findings LO positively influenced OCB. Team-oriented culture moderated the relationship between having a LO and OCB. Originality/value This study helps explain how to achieve a LO in a context of high power distance and collectivist culture such as Malaysia. This study also highlights the importance of the anticipated synergistic effects of a LO and team-oriented culture in promoting OCB.

scholarly journals A Whole Genome Re-Sequencing Based GWA Analysis Reveals Candidate Genes Associated with Ivermectin Resistance in Haemonchus contortus

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 367 ◽  
Author(s):  
Sawar Khan ◽  
Ayesha Nisar ◽  
Jianqi Yuan ◽  
Xiaoping Luo ◽  
Xueqin Dou ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Haemonchus Contortus ◽  
Population Genomics ◽  
Small Ruminants ◽  
Track Record ◽  
Genome Wide ◽  
Signatures Of Selection ◽  
Parasitic Worms ◽  
Important Parasite

The most important and broad-spectrum drug used to control the parasitic worms to date is ivermectin (IVM). Resistance against IVM has emerged in parasites, and preserving its efficacy is now becoming a serious issue. The parasitic nematode Haemonchus contortus (Rudolphi, 1803) is economically an important parasite of small ruminants across the globe, which has a successful track record in IVM resistance. There are growing evidences regarding the multigenic nature of IVM resistance, and although some genes have been proposed as candidates of IVM resistance using lower magnification of genome, the genetic basis of IVM resistance still remains poorly resolved. Using the full magnification of genome, we herein applied a population genomics approach to characterize genome-wide signatures of selection among pooled worms from two susceptible and six ivermectin-resistant isolates of H. contortus, and revealed candidate genes under selection in relation to IVM resistance. These candidates also included a previously known IVM-resistance-associated candidate gene HCON_00148840, glc-3. Finally, an RNA-interference-based functional validation assay revealed the HCON_00143950 as IVM-tolerance-associated gene in H. contortus. The possible role of this gene in IVM resistance could be detoxification of xenobiotic in phase I of xenobiotic metabolism. The results of this study further enhance our understanding on the IVM resistance and continue to provide further evidence in favor of multigenic nature of IVM resistance.

The Possible Role of Hydroxylation in the Detoxification of Atrazine in Mature Vetiver (Chrysopogon zizanioides Nash) Grown in Hydroponics

2005 ◽  
Vol 60 (5-6) ◽  
pp. 427-434 ◽  
Author(s):  
Sylvie Marcacci ◽  
Muriel Raveton ◽  
Patrick Ravanel ◽  
Jean-Paul Schwitzguébel
Keyword(s):  
Cytochromes P450 ◽  
Resistance Mechanism ◽  
Uv Spectra ◽  
Chrysopogon Zizanioides ◽  
Retention Factors ◽  
Glutathione S Transferases ◽  
Layer Chromatography ◽  
Major Metabolic Pathway

The resistance mechanism of vetiver (Chrysopogon zizanioides) to atrazine was investigated to evaluate its potential for phytoremediation of environment contaminated with the herbicide. Plants known to metabolise atrazine rely on hydroxylation mediated by benzoxazinones, conjugation catalyzed by glutathione-S-transferases and dealkylation probably mediated by cytochromes P450. All three possibilities were explored in mature vetiver grown in hydroponics during this research project. Here we report on the chemical role of benzoxazinones in the transformation of atrazine.Fresh vetiver roots and leaves were cut to extract and study their content in benzoxazinones known to hydroxylate atrazine, such as 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)- one (DIBOA), 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) and their mono- and di-glucosylated forms. Identification of benzoxazinones was performed by thin layer chromatography (TLC) and comparison of retention factors (Rf) and UV spectra with standards: although some products exhibited the same Rf as standards, UV spectra were different. Furthermore, in vitro hydroxylation of atrazine could not be detected in the presence of vetiver extracts. Finally, vetiver organs exposed to [14C]-atrazine did not produce any significant amount of hydroxylated products, such as hydroxyatrazine (HATR), hydroxydeethylatrazine (HDEA), and hydroxy-deisopropylatrazine (HDIA). Altogether, these metabolic features suggest that hydroxylation was not a major metabolic pathway of atrazine in vetiver.

scholarly journals Protective Role of Naturally Occurring Interleukin-17A-Producing γδ T Cells in the Lung at the Early Stage of Systemic Candidiasis in Mice

2011 ◽  
Vol 79 (11) ◽  
pp. 4503-4510 ◽  
Author(s):  
Takashi Dejima ◽  
Kensuke Shibata ◽  
Hisakata Yamada ◽  
Hiromitsu Hara ◽  
Yoichiro Iwakura ◽  
...  
Keyword(s):  
T Cells ◽  
Early Stage ◽  
Γδ T Cells ◽  
Protective Role ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Content Type ◽  
Naturally Occurring ◽  
Interleukin 17A

ABSTRACTInterleukin-17A (IL-17A)-producing γδ T cells differentiate in the fetal thymus and reside in the peripheral tissues, such as the lungs of naïve adult mice. We show here that naturally occurring γδ T cells play a protective role in the lung at a very early stage after systemic infection withCandida albicans.Selective depletion of neutrophils byin vivoadministration of anti-Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the lung than in the kidney 24 h after intravenous infection withC. albicans.Rapid and transient production of IL-23 was detected in the lung at 12 h, preceding IL-17A production and the influx of neutrophils, which reached a peak at 24 h after infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils concurrently with impaired fungal clearance in the lung after infection. The major source of IL-17A was the γδ T cell population in the lung, and Cδ KO mice showed little IL-17A production and reduced neutrophil infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for IL-17A production by γδ T cells. Thus, our study demonstrated a novel role of naturally occurring IL-17A-producing γδ T cells in the first line of host defense againstC. albicansinfection.

scholarly journals Protective Role of Akt2 in Salmonella enterica Serovar Typhimurium-Induced Gastroenterocolitis

2011 ◽  
Vol 79 (7) ◽  
pp. 2554-2566 ◽  
Author(s):  
Winnie W. S. Kum ◽  
Bernard C. Lo ◽  
Hong B. Yu ◽  
B. Brett Finlay
Keyword(s):  
Salmonella Enterica ◽  
Annexin V ◽  
Immunohistochemical Analysis ◽  
Neutrophil Infiltration ◽  
Protective Role ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTTheSalmonellaeffector protein SopB has previously been shown to induce activation of Akt and protect epithelial cells from apoptosisin vitro. To characterize the role of Akt2 in host defense againstSalmonella entericaserovar Typhimurium infection, wild-type (WT) mice and mice lacking Akt2 (Akt2 knockout [KO] mice) were infected using aSalmonellaacute gastroenteritis model. Infected Akt2 KO mice showed a more pronounced morbidity and mortality associated with higher bacterial loads in the intestines and elevated levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and MCP-1, in the colons at 1 day postinfection compared to those shown in WT mice. Histopathological assessment and immunohistochemical analysis of cecal sections at 1 day postinfection revealed more severe inflammation and higher levels of neutrophil infiltration in the ceca of Akt2 KO mice. Flow cytometry analysis further confirmed an increase in the recruitment of Gr-1+CD11b+neutrophils and F4/80+CD11b+macrophages in the intestines of infected Akt2 KO mice. Additionally, enhanced levels of annexin V+and terminal transferase dUTP nick end labeling-positive (TUNEL+) apoptotic cells in the intestines of infected Akt2 KO mice were also observed, indicating that Akt2 plays an essential role in protection against apoptosis. Finally, the differences in bacterial loads and cecal inflammation in WT and Akt2 KO mice infected with WTSalmonellawere abolished when these mice were infected with thesopBdeletion mutant, indicating that SopB may play a role in protecting the mice fromSalmonellainfection through the activation of Akt2. These data demonstrate a definitive phenotypic abnormality in the innate response in mice lacking Akt2, underscoring the important protective role of Akt2 inSalmonellainfection.

scholarly journals The Protective Role of 1,8-Dihydroxynaphthalene–Melanin on Conidia of the Opportunistic Human Pathogen Aspergillus fumigatus Revisited: No Role in Protection against Hydrogen Peroxide and Superoxides

mSphere ◽  
2022 ◽  
Author(s):  
E. M. Keizer ◽  
I. D. Valdes ◽  
B. L. McCann ◽  
E. M. Bignell ◽  
H. A. B. Wösten ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Aspergillus Fumigatus ◽  
Protective Role ◽  
Oxygen Species ◽  
Human Pathogen ◽  
Opportunistic Pathogens ◽  
Green Pigment ◽  
Content Type ◽  
Opportunistic Human Pathogen

Opportunistic pathogens like Aspergillus fumigatus have strategies to protect themselves against reactive oxygen species like hydrogen peroxides and superoxides that are produced by immune cells. DHN-melanin is the green pigment on conidia of Aspergillus fumigatus and more than 2 decades ago was reported to protect conidia against hydrogen peroxide.

scholarly journals Intestinally Secreted C-Type Lectin Reg3b Attenuates Salmonellosis but Not Listeriosis in Mice

2012 ◽  
Vol 80 (3) ◽  
pp. 1115-1120 ◽  
Author(s):  
Marleen T. J. van Ampting ◽  
Linda M. P. Loonen ◽  
Arjan J. Schonewille ◽  
Irene Konings ◽  
Carolien Vink ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Salmonella Enteritidis ◽  
Ex Vivo ◽  
Protective Role ◽  
Carbohydrate Binding ◽  
Intestinal Infection ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type

The Reg3 protein family, including the human member designated pancreatitis-associated protein (PAP), consists of secreted proteins that contain a C-type lectin domain involved in carbohydrate binding. They are expressed by intestinal epithelial cells. Colonization of germ-free mice and intestinal infection with pathogens increase the expression of Reg3g and Reg3b in the murine ileum. Reg3g is directly bactericidal for Gram-positive bacteria, but the exact role of Reg3b in bacterial infections is unknown. To investigate the possible protective role of Reg3b in intestinal infection, Reg3b knockout (Reg3b−/−) mice and wild-type (WT) mice were orally infected with Gram-negativeSalmonella enteritidisor Gram-positiveListeria monocytogenes. At day 2 after oralListeriainfection and at day 4 after oralSalmonellainfection, mice were sacrificed to collect intestinal and other tissues for pathogen quantification. Protein expression of Reg3b and Reg3g was determined in intestinal mucosal scrapings of infected and noninfected mice. In addition,ex vivobinding of ileal mucosal Reg3b toListeriaandSalmonellawas investigated. Whereas recovery ofSalmonellaorListeriafrom feces of Reg3b−/−mice did not differ from that from feces of WT mice, significantly higher numbers of viableSalmonella, but notListeria, bacteria were recovered from the colon, mesenteric lymph nodes, spleen, and liver of the Reg3b−/−mice than from those of WT mice. Mucosal Reg3b binds to both bacterial pathogens and may interfere with their mode of action. Reg3b plays a protective role against intestinal translocation of the Gram-negative bacteriumS. enteritidisin mice but not against the Gram-positive bacteriumL. monocytogenes.

scholarly journals GES-18, a New Carbapenem-Hydrolyzing GES-Type β-Lactamase from Pseudomonas aeruginosa That Contains Ile80 and Ser170 Residues

2012 ◽  
Vol 57 (1) ◽  
pp. 396-401 ◽  
Author(s):  
Carine Bebrone ◽  
Pierre Bogaerts ◽  
Heinrich Delbrück ◽  
Sandra Bennink ◽  
Michaël B. Kupper ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Lower Respiratory Tract ◽  
Resistance Mechanism ◽  
Single Amino Acid ◽  
Content Type ◽  
Reference Center ◽  
National Reference ◽  
National Reference Center ◽  
Similar Kinetic

ABSTRACTA clinical isolate ofPseudomonas aeruginosarecovered from the lower respiratory tract of an 81-year-old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme GES-5 by a single amino acid substitution (Val80Ile, in the numbering according to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and cefoxitin with similar kinetic parameters and that GES-18 was less susceptible than GES-1 to classical β-lactamase inhibitors such as clavulanate and tazobactam. The overall structure of GES-18 is similar to the solved structures of GES-1 and GES-2, the Val80Ile and Gly170Ser substitutions causing only subtle local rearrangements. Notably, the hydrolytic water molecule and the Glu166 residue were slightly displaced compared to their counterparts in GES-1. Our kinetic and crystallographic data for GES-18 highlight the pivotal role of the Gly170Ser substitution which distinguishes GES-5 and GES-18 from GES-1.

scholarly journals Protective Role of Spore Structural Components in Determining Bacillus subtilis Spore Resistance to Simulated Mars Surface Conditions

2012 ◽  
Vol 78 (24) ◽  
pp. 8849-8853 ◽  
Author(s):  
Ralf Moeller ◽  
Andrew C. Schuerger ◽  
Günther Reitz ◽  
Wayne L. Nicholson
Keyword(s):  
Bacillus Subtilis ◽  
Dipicolinic Acid ◽  
Protective Role ◽  
Structural Components ◽  
Wild Type ◽  
Content Type ◽  
Surface Conditions ◽  
Bacillus Subtilis Spore ◽  
Spore Resistance

ABSTRACTSpores of wild-type and mutantBacillus subtilisstrains lacking various structural components were exposed to simulated Martian atmospheric and UV irradiation conditions. Spore survival and mutagenesis were strongly dependent on the functionality of all of the structural components, with small acid-soluble spore proteins, coat layers, and dipicolinic acid as key protectants.

scholarly journals Role of the Tet38 Efflux Pump in Staphylococcus aureus Internalization and Survival in Epithelial Cells

2015 ◽  
Vol 83 (11) ◽  
pp. 4362-4372 ◽  
Author(s):  
Q. C. Truong-Bolduc ◽  
G. R. Bolduc ◽  
H. Medeiros ◽  
J. M. Vyas ◽  
Y. Wang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Unsaturated Fatty Acids ◽  
Efflux Pump ◽  
Fold Increase ◽  
Growth Patterns ◽  
Heart Cell ◽  
Content Type

ABSTRACTWe previously identified the protein Tet38 as a chromosomally encoded efflux pump ofStaphylococcus aureusthat confers resistance to tetracycline and certain unsaturated fatty acids. Tet38 also contributes to mouse skin colonization. In this study, we discovered a novel regulator oftet38, named tetracycline regulator 21 (TetR21), that bound specifically to thetet38promoter and repressed pump expression. A ΔtetR21mutant showed a 5-fold increase intet38transcripts and an 8-fold increase in resistance to tetracycline and fatty acids. The global regulator MgrA bound to thetetR21promoter and indirectly repressed the expression oftet38. To further assess the full role of Tet38 inS. aureusadaptability, we tested its effect on host cell invasion using A549 (lung) and HMEC-1 (heart) cell lines. We usedS. aureusRN6390, its Δtet38, ΔtetR21, and ΔmgrAmutants, and a Δtet38 ΔtetR21double mutant. After 2 h of contact, the Δtet38mutant was internalized in 6-fold-lower numbers than RN6390 in A549 and HMEC-1 cells, and the ΔtetR21mutant was internalized in 2-fold-higher numbers than RN6390. A slight increase of 1.5-fold in internalization was found for the ΔmgrAmutant. The growth patterns of RN6390 and the ΔmgrAand ΔtetR21mutants within A549 cells were similar, while no growth was observed for the Δtet38mutant. These data indicate that the Tet38 efflux pump is regulated by TetR21 and contributes to the ability ofS. aureusto internalize and replicate within epithelial cells.

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