scholarly journals Evaluation of Thio- and Seleno-Acetamides Bearing Benzenesulfonamide as Inhibitor of Carbonic Anhydrases from Different Pathogenic Bacteria

2020 ◽  
Vol 21 (2) ◽  
pp. 598 ◽  
Author(s):  
Andrea Angeli ◽  
Mariana Pinteala ◽  
Stelian S. Maier ◽  
Bogdan C. Simionescu ◽  
Andrea Milaneschi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Carbonic Anhydrase ◽  
Burkholderia Pseudomallei ◽  
Pathogenic Bacteria ◽  
Antibacterial Agents ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Physiological Role ◽  
Carbonic Anhydrases ◽  
Serovar Typhimurium ◽  
Isoform Selectivity

A series of 2-thio- and 2-seleno-acetamides bearing the benzenesulfonamide moiety were evaluated as Carbonic Anhydrase (CA, EC 4.2.1.1) inhibitors against different pathogenic bacteria such as the Vibrio cholerae (VchCA-α and VchCA-β), Burkholderia pseudomallei (BpsCA-β and BpsCA-γ), Mycobacterium tuberculosis (Rv3723-β) and the Salmonella enterica serovar Typhimurium (StCA2-β). The molecules represent interesting leads worth developing as innovative antibacterial agents since they possess new mechanism of action and isoform selectivity preferentially against the bacterial expressed CAs. The identification of potent and selective inhibitors of bacterial CAs may lead to tools also useful for deciphering the physiological role(s) of such proteins.

scholarly journals Cystathionine β-Lyase Is Important for Virulence of Salmonella enterica Serovar Typhimurium

2004 ◽  
Vol 72 (6) ◽  
pp. 3310-3314 ◽  
Author(s):  
Linda J. Ejim ◽  
Vanessa M. D'Costa ◽  
Nadine H. Elowe ◽  
J. Concepción Loredo-Osti ◽  
Danielle Malo ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Biosynthetic Pathway ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Infection ◽  
Bacterial Virulence ◽  
Methionine Biosynthesis ◽  
Insertional Inactivation ◽  
Serovar Typhimurium

ABSTRACT The biosynthesis of methionine in bacteria requires the mobilization of sulfur from Cys by the formation and degradation of cystathionine. Cystathionine β-lyase, encoded by metC in bacteria and STR3 in Schizosaccharomyces pombe, catalyzes the breakdown of cystathionine to homocysteine, the penultimate step in methionine biosynthesis. This enzyme has been suggested to be the target for pyridinamine antimicrobial agents. We have demonstrated, by using purified enzymes from bacteria and yeast, that cystathionine β-lyase is not the likely target of these agents. Nonetheless, an insertional inactivation of metC in Salmonella enterica serovar Typhimurium resulted in the attenuation of virulence in a mouse model of systemic infection. This result confirms a previous chemical validation of the Met biosynthetic pathway as a target for the development of antibacterial agents and demonstrates that cystathionine β-lyase is important for bacterial virulence.

Overexpression, purification, crystallization and preliminary structural study of dTDP-6-deoxy-L-lyxo-4-hexulose reductase (RmlD), the fourth enzyme of the dTDP-L-rhamnose synthesis pathway, from Salmonella enterica serovar Typhimurium

1999 ◽  
Vol 55 (12) ◽  
pp. 2043-2046 ◽  
Author(s):  
Marie-France Giraud ◽  
Helen J. McMiken ◽  
Gordon A. Leonard ◽  
Paul Messner ◽  
Chris Whitfield ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Wall ◽  
Recombinant Protein ◽  
Salmonella Enterica ◽  
Pathogenic Bacteria ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Diffusion Method ◽  
Vapour Diffusion ◽  
Serovar Typhimurium ◽  
Orthorhombic Crystals

L-Rhamnose is an essential component of the cell wall of many pathogenic bacteria. Its precursor, dTDP-L-rhamnose, is synthesized from α-D-glucose-1-phosphate and dTTP via a pathway requiring four distinct enzymes: RmlA, RmlB, RmlC and RmlD. RmlD catalyses the terminal step of this pathway by converting dTDP-6-deoxy-L-lyxo-4-hexulose to dTDP-L-rhamnose. RmlD from Salmonella enterica serovar Typhimurium has been overexpressed in Escherichia coli. The recombinant protein was purified by a two-step protocol involving anion-exchange and hydrophobic chromatography. Dynamic light-scattering experiments indicated that the recombinant protein is monodisperse. Crystals of native and selenomethionine-enriched RmlD have been obtained using the sitting-drop vapour-diffusion method with polyethylene glycol as precipitant. Diffraction data have been collected from orthorhombic crystals of both native and selenomethionyl-derivatized protein, allowing tracing of the protein structure.

scholarly journals Exopolysaccharides Produced by Probiotic Strains Modify the Adhesion of Probiotics and Enteropathogens to Human Intestinal Mucus

2006 ◽  
Vol 69 (8) ◽  
pp. 2011-2015 ◽  
Author(s):  
PATRICIA RUAS-MADIEDO ◽  
MIGUEL GUEIMONDE ◽  
ABELARDO MARGOLLES ◽  
CLARA G. de los REYES-GAVILÁN ◽  
SEPPO SALMINEN
Keyword(s):  
Salmonella Enterica Serovar Typhimurium ◽  
Bifidobacterium Longum ◽  
Lactobacillus Rhamnosus ◽  
Physiological Role ◽  
Adhesion Properties ◽  
Bifidobacterium Animalis ◽  
Intestinal Mucus ◽  
Serovar Typhimurium ◽  
Probiotic Strains ◽  
Encoding Genes

Exopolysaccharides (EPSs) are exocellular polymers present in the surface of many bacteria, including Lactobacillus and Bifidobacterium. The genome sequence of several strains revealed the presence of EPS-encoding genes. However, the physiological role that EPSs play in the bacterial ecology still remains uncertain. In this study, we have assessed the effect of EPSs produced by Lactobacillus rhamnosus GG, Bifidobacterium longum NB667, and Bifidobacterium animalis IPLA-R1 on the adhesion of probiotic and enteropathogen strains to human intestinal mucus. The EPS fraction GG had no significant effect on the adhesion of L. rhamnosus GG and B. animalis IPLA-R1. However, the EPS fractions NB667 and IPLA-R1 significantly reduced the adherence of both probiotic strains. In contrast, the three EPS fractions increased the adhesion of Enterobacter sakazakii ATCC 29544 and Escherichia coli NCTC 8603. Higher adherence of Salmonella enterica serovar Typhimurium ATCC 29631 and Clostridium difficile ATCC 9689 was detected in the presence of the EPS fractions GG and NB667. In general, these effects were obtained at EPS concentrations of up to 5 mg/ml, and they were EPS dose dependent. The competitive exclusion of probiotics in the presence of EPS could suggest the involvement of these biopolymers in the adhesion to mucus. The increase in the adherence of enteropathogens could be explained if components of the pathogen surface are able to bind to specific EPSs and the bound EPSs are able to adhere to mucus. To the best of our knowledge, this is the first work reporting the effect of EPSs from probiotics on bacterial adhesion properties.

scholarly journals H-NS is a part of a thermally controlled mechanism for bacterial gene regulation

2005 ◽  
Vol 391 (2) ◽  
pp. 203-213 ◽  
Author(s):  
Shusuke Ono ◽  
Martin D. Goldberg ◽  
Tjelvar Olsson ◽  
Diego Esposito ◽  
Jay C. D. Hinton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thermal Activation ◽  
Pathogenic Bacteria ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Virulence Gene ◽  
Bacterial Gene ◽  
Virulence Gene Expression ◽  
Serovar Typhimurium ◽  
Micro Organisms ◽  
Dna Binding Properties

Temperature is a primary environmental stress to which micro-organisms must be able to adapt and respond rapidly. Whereas some bacteria are restricted to specific niches and have limited abilities to survive changes in their environment, others, such as members of the Enterobacteriaceae, can withstand wide fluctuations in temperature. In addition to regulating cellular physiology, pathogenic bacteria use temperature as a cue for activating virulence gene expression. This work confirms that the nucleoid-associated protein H-NS (histone-like nucleoid structuring protein) is an essential component in thermoregulation of Salmonella. On increasing the temperature from 25 to 37 °C, more than 200 genes from Salmonella enterica serovar Typhimurium showed H-NS-dependent up-regulation. The thermal activation of gene expression is extremely rapid and change in temperature affects the DNA-binding properties of H-NS. The reduction in gene repression brought about by the increase in temperature is concomitant with a conformational change in the protein, resulting in the decrease in size of high-order oligomers and the appearance of increasing concentrations of discrete dimers of H-NS. The present study addresses one of the key complex mechanisms by which H-NS regulates gene expression.

scholarly journals In vitro synergistic potentials of novel antibacterial combination therapies against Salmonella enterica serovar Typhimurium

2020 ◽  
Author(s):  
Md. Akil Hossain ◽  
Hae-Chul Park ◽  
Kwang-jick Lee ◽  
Sung-Won Park ◽  
Seung-Chun Park ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Pathogenic Bacteria ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Clinical Importance ◽  
Farm Animals ◽  
Health Concern ◽  
Epicatechin Gallate ◽  
Serovar Typhimurium

Abstract Background: The antibiotics generally used in farm animals are rapidly losing their effectiveness all over the world as bacteria develop antibiotic resistance. Like some other pathogenic bacteria multidrug-resistant strains of Salmonella enterica serovar Typhimurium (S. Typhimurium) are also frequently found in animals and humans which poses a major public health concern. New strategies are needed to block the development of resistance and to prolong the life of traditional antibiotics. Thus, this study aimed to increase the efficacy of existing antibiotics against S. Typhimurium by combining them with opportunistic phenolic compounds gallic acid (GA), epicatechin, epicatechin gallate, epigallocatechin and hamamelitannin. Fractional inhibitory concentration indexes (FICI) of phenolic compound-antibiotic combinations against S. Typhimurium were determined. Based on the FICI and clinical importance, 1 combination (GA and ceftiofur) was selected for evaluating its effects on the virulence factors of this bacterium. Viability of Rattus norvegicus (IEC-6) cell in presence of this antibacterial combination was evaluated.Results: Minimum inhibitory concentrations (MICs) of GA, epigallocatechin and hamamelitannin found against different strains of S. Typhimurium were 256, (512–1024), and (512–1024) μg/mL, respectively. Synergistic antibacterial effect was obtained from the combination of erythromycin-epicatechin gallate (FICI: 0.50) against S. Typhimurium. Moreover, additive effects (FICI: 0.502–0.750) were obtained from 16 combinations against this bacterium. The time-kill assay and ultrastructural morphology showed that GA-ceftiofur combination more efficiently inhibited the growth of S. Typhimurium compared to individual antimicrobials. Biofilm viability, and swimming and swarming motilities of S. Typhimurium in presence of GA-ceftiofur combination were more competently inhibited than individual antimicrobials. Viabilities of IEC-6 cells were more significantly enhanced by GA-ceftiofur combinations than these antibacterials alone.Conclusions: This study suggests that GA-ceftiofur combination can be potential medication to treat S. Typhimurium-associated diarrhea and prevent S. Typhimurium-associated blood-stream infections (e.g.: fever) in farm animals, and ultimately its transmission from animal to human. Further in vivo study to confirm these effects and safety profiles in farm animal should be undertaken for establishing these combinations as medications.

scholarly journals Transgenic expression of carbonic anhydrase III in cardiac muscle demonstrates a mechanism to tolerate acidosis

2019 ◽  
Vol 317 (5) ◽  
pp. C922-C931 ◽  
Author(s):  
Han-Zhong Feng ◽  
J.-P. Jin
Keyword(s):  
Carbonic Anhydrase ◽  
Transgenic Mice ◽  
Intracellular Ph ◽  
Skeletal Muscles ◽  
Ex Vivo ◽  
Physiological Role ◽  
Wild Type Mouse ◽  
Carbonic Anhydrases ◽  
Wild Type ◽  
Carbonic Anhydrase Iii

Carbonic anhydrase III (CAIII) is abundant in liver, adipocytes, and skeletal muscles, but not heart. A cytosolic enzyme that catalyzes conversions between CO2 and [Formula: see text] in the regulation of intracellular pH, its physiological role in myocytes is not fully understood. Mouse skeletal muscles lacking CAIII showed lower intracellular pH during fatigue, suggesting its function in stress tolerance. We created transgenic mice expressing CAIII in cardiomyocytes that lack endogenous CAIII. The transgenic mice showed normal cardiac development and life span under nonstress conditions. Studies of ex vivo working hearts under normal and acidotic conditions demonstrated that the transgenic and wild-type mouse hearts had similar pumping functions under normal pH. At acidotic pH, however, CAIII transgenic mouse hearts showed significantly less decrease in cardiac function than that of wild-type control as shown by higher ventricular pressure development, systolic and diastolic velocities, and stroke volume via elongating the time of diastolic ejection. In addition to the effect of introducing CAIII into cardiomyocytes on maintaining homeostasis to counter acidotic stress, the results demonstrate the role of carbonic anhydrases in maintaining intracellular pH in muscle cells as a potential mechanism to treat heart failure.

scholarly journals Antibiotic Resistance in Salmonella enterica Serovar Typhimurium Exposed to Microcin-Producing Escherichia coli

2001 ◽  
Vol 67 (8) ◽  
pp. 3763-3766 ◽  
Author(s):  
Steve A. Carlson ◽  
Timothy S. Frana ◽  
Ronald W. Griffith
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Salmonella Enterica ◽  
Pathogenic Bacteria ◽  
Defense Mechanism ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Multidrug Resistant ◽  
E Coli ◽  
Resistant Phenotype ◽  
Serovar Typhimurium

ABSTRACT Microcin 24 is an antimicrobial peptide secreted by uropathogenicEscherichia coli. Secretion of microcin 24 provides an antibacterial defense mechanism for E. coli. In a plasmid-based system using transformed Salmonella enterica, we found that resistance to microcin 24 could be seen in concert with a multiple-antibiotic resistance phenotype. This multidrug-resistant phenotype appeared when Salmonella was exposed to an E. coli strain expressing microcin 24. Therefore, it appears that multidrug-resistant Salmonellacan arise as a result of an insult from other pathogenic bacteria.

scholarly journals Cryptococcus neoformans Senses CO2 through the Carbonic Anhydrase Can2 and the Adenylyl Cyclase Cac1

2006 ◽  
Vol 5 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Estelle Gewiss Mogensen ◽  
Guilhem Janbon ◽  
James Chaloupka ◽  
Clemens Steegborn ◽  
Man Shun Fu ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Adenylyl Cyclase ◽  
Cryptococcus Neoformans ◽  
Fungal Pathogen ◽  
Natural Habitat ◽  
Physiological Role ◽  
Immunocompromised Patients ◽  
Structural Studies ◽  
Carbonic Anhydrases ◽  
Spontaneous Reaction

ABSTRACT Cryptococcus neoformans, a fungal pathogen of humans, causes fatal meningitis in immunocompromised patients. Its virulence is mainly determined by the elaboration of a polysaccharide capsule surrounding its cell wall. During its life, C. neoformans is confronted with and responds to dramatic variations in CO2 concentrations; one important morphological change triggered by the shift from its natural habitat (0.033% CO2) to infected hosts (5% CO2) is the induction of capsule biosynthesis. In cells, CO2 is hydrated to bicarbonate in a spontaneous reaction that is accelerated by carbonic anhydrases. Here we show that C. neoformans contains two β-class carbonic anhydrases, Can1 and Can2. We further demonstrate that CAN2, but not CAN1, is abundantly expressed and essential for the growth of C. neoformans in its natural environment, where CO2 concentrations are limiting. Structural studies reveal that Can2 forms a homodimer in solution. Our data reveal Can2 to be the main carbonic anhydrase and suggest a physiological role for bicarbonate during C. neoformans growth. Bicarbonate directly activates the C. neoformans Cac1 adenylyl cyclase required for capsule synthesis. We show that this specific activation is optimal at physiological pH.

scholarly journals Sensitivity of enrichment-PCR method for Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis analysis in chicken carcasses

Food Research ◽  
2021 ◽  
Vol 5 (2) ◽  
pp. 54-61
Author(s):  
H.A. Wulan ◽  
Nurjanah S. ◽  
W.P. Rahayu
Keyword(s):  
Salmonella Enterica ◽  
Pathogenic Bacteria ◽  
Target Genes ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Salmonella Enterica Serovar Enteritidis ◽  
Salmonella Spp ◽  
High Prevalence ◽  
Serovar Typhimurium ◽  
Peptone Water ◽  
Pcr Method

Salmonella spp. is Gram negative-pathogenic bacteria that usually found as a contaminant in chicken carcasses. This study was aimed to increase the sensitivity of PCR enrichment step and apply the enrichment-PCR combination to detect Salmonella in chicken carcasses. In this study were used Salmonella enterica serovar Hadar, Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis with the target genes were invA, STM4497, and respectively. A total of 25 g of the chicken carcasses were artificially contaminated by approximately 0.96 and 3.33 MPN/mL for each serovar separately. Samples were incubated in pre-enrichment and enrichment media for 8 hrs prior to the DNA extraction. The pre-enrichment and enrichment media was Buffered Peptone Water and Rappaport-Vassiliadis-soya. The result showed that the target genes of S. enterica ser. Hadar, S. enterica ser. Typhimurium and S. enterica ser. Enteritidis were detected in chicken carcasses, indicated by the presence of DNA band with the size was 429 bp, 311 bp and 135 bp respectively. These result in line with analysis using ISO method and BLAST-comparison analysis of DNA amplicon sequences with GenBank references. Application of this method for Salmonella detection in chicken carcasses sold in the traditional market showed a higher prevalence than the previous result without enrichment. All samples (n = 100) from unsanitary practice sellers were positively contaminated by Salmonella spp. and also high prevalence for S. enterica ser. Typhimurium and S. enterica ser. Enteritidis. It can be concluded that enrichment is an important step to increase the sensitivity detection of PCR method.

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