Exploitation of Peptide Transport Systems in the Design of Antimicrobial Agents

1992 ◽  
pp. 127-142 ◽  
Author(s):  
D. R. Tyreman ◽  
M. W. Smith ◽  
G. M. Payne ◽  
J. W. Payne
Keyword(s):  
Antimicrobial Agents ◽  
Peptide Transport ◽  
Transport Systems

scholarly journals Functional Characterization of the Proteolytic System of Lactobacillus sanfranciscensis DSM 20451T during Growth in Sourdough

2005 ◽  
Vol 71 (10) ◽  
pp. 6260-6266 ◽  
Author(s):  
Nicoline Vermeulen ◽  
Melanie Pavlovic ◽  
Matthias A. Ehrmann ◽  
Michael G. Gänzle ◽  
Rudi F. Vogel
Keyword(s):  
Amino Acid ◽  
Proteolytic Activity ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Peptide Transport ◽  
Transport Systems ◽  
Peptide Hydrolysis ◽  
Degenerate Primers ◽  
Lactobacillus Sanfranciscensis ◽  
Peptide Uptake

ABSTRACT Protein hydrolysis and amino acid metabolism contribute to the beneficial effects of sourdough fermentation on bread quality. In this work, genes of Lactobacillus sanfranciscensis strain DSM 20451 involved in peptide uptake and hydrolysis were identified and their expression during growth in sourdough was determined. Screening of the L. sanfranciscensis genome with degenerate primers targeting prt and analysis of proteolytic activity in vitro provided no indication for proteolytic activity. Proteolysis in aseptic doughs and sourdoughs fermented with L. sanfranciscensis was inhibited upon the addition of an aspartic protease inhibitor. These results indicate that proteolysis was not linked to the presence of L. sanfranciscensis DSM 20451 and that this strain does not harbor a proteinase. Genes encoding the peptide transport systems Opp and DtpT and the intracellular peptidases PepT, PepR, PepC, PepN, and PepX were identified. Both peptide uptake systems and the genes pepN, pepX, pepC, and pepT were expressed by L. sanfranciscensis growing exponentially in sourdough, whereas pepX was not transcribed. The regulation of the expression of Opp, DtpT, and PepT during growth of L. sanfranciscensis in sourdough was investigated. Expression of Opp and DtpT was reduced approximately 17-fold when the peptide supply in dough was increased. The expression of PepT was dependent on the peptide supply to a lesser extent. Thus, the accumulation of amino nitrogen by L. sanfranciscensis in dough is attributable to peptide hydrolysis rather than proteolysis and amino acid metabolism by L. sanfranciscensis during growth in sourdough is limited by the peptide availability.

scholarly journals Proteomic Signature of Lactococcus lactis NCDO763 Cultivated in Milk

2005 ◽  
Vol 71 (11) ◽  
pp. 7152-7163 ◽  
Author(s):  
Christophe Gitton ◽  
Mickael Meyrand ◽  
Juhui Wang ◽  
Christophe Caron ◽  
Alain Trubuil ◽  
...  
Keyword(s):  
De Novo ◽  
Synthetic Medium ◽  
Skim Milk ◽  
Peptide Transport ◽  
Transport Systems ◽  
Nitrogenous Compounds ◽  
Proteomic Data ◽  
Defective Mutant ◽  
Essential Enzyme ◽  
Cell Envelopes

ABSTRACT We have compared the proteomic profiles of L. lactis subsp. cremoris NCDO763 growing in the synthetic medium M17Lac, skim milk microfiltrate (SMM), and skim milk. SMM was used as a simple model medium to reproduce the initial phase of growth of L. lactis in milk. To widen the analysis of the cytoplasmic proteome, we used two different gel systems (pH ranges of 4 to 7 and 4.5 to 5.5), and the proteins associated with the cell envelopes were also studied by two-dimensional electrophoresis. In the course of the study, we analyzed about 800 spots and identified 330 proteins by mass spectrometry. We observed that the levels of more than 50 and 30 proteins were significantly increased upon growth in SMM and milk, respectively. The large redeployment of protein synthesis was essentially associated with an activation of pathways involved in the metabolism of nitrogenous compounds: peptidolytic and peptide transport systems, amino acid biosynthesis and interconversion, and de novo biosynthesis of purines. We also showed that enzymes involved in reactions feeding the purine biosynthetic pathway in one-carbon units and amino acids have an increased level in SMM and milk. The analysis of the proteomic data suggested that the glutamine synthetase (GS) would play a pivotal role in the adaptation to SMM and milk. The analysis of glnA expression during growth in milk and the construction of a glnA-defective mutant confirmed that GS is an essential enzyme for the development of L. lactis in dairy media. This analysis thus provides a proteomic signature of L. lactis, a model lactic acid bacterium, growing in its technological environment.

scholarly journals Homeostasis of Glutathione Is Associated with Polyamine-Mediated β-Lactam Susceptibility in Acinetobacter baumannii ATCC 19606

2013 ◽  
Vol 57 (11) ◽  
pp. 5457-5461 ◽  
Author(s):  
Dong H. Kwon ◽  
Saboor Hekmaty ◽  
Gomattie Seecoomar
Keyword(s):  
Acinetobacter Baumannii ◽  
Redox State ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Transport Systems ◽  
Toxic Substances ◽  
Cellular Redox ◽  
Content Type ◽  
Intracellular Glutathione ◽  
Cellular Redox State

ABSTRACTGlutathione is a tripeptide (l-γ-glutamyl–l-cysteinyl–glycine) thiol compound existing in many bacteria and maintains a proper cellular redox state, thus protecting cells against toxic substances such as reactive oxygen species. Polyamines (spermine and spermidine) are low-molecular-weight aliphatic polycations ubiquitously presenting in all living cells and modulate many cellular functions. We previously reported that exogenous polyamines significantly enhanced β-lactam susceptibility of β-lactam-associated multidrug-resistantAcinetobacter baumannii. In this study, three genes differentially associated with the polyamine effects on β-lactam susceptibility were identified by transposon mutagenesis ofA. baumanniiATCC 19606. All three genes encoded components of membrane transport systems. Inactivation of one of the genes encoding a putative glutathione transport ATP-binding protein increased the accumulation of intracellular glutathione (∼150 to ∼200%) and significantly decreased the polyamine effects on β-lactam susceptibility inA. baumanniiATCC 19606. When the cells were grown with polyamines, the levels of intracellular glutathione inA. baumanniiATCC 19606 significantly decreased from ∼0.5 to ∼0.2 nmol, while the levels of extracellular glutathione were correspondingly increased. However, the levels of total glutathione (intra- plus extracellular) were unchanged when the cells were grown with or without polyamines. Overall, these results suggest that exogenous polyamines induce glutathione export, resulting in decreased levels of intracellular glutathione, which may produce an improper cellular redox state that is associated with the polyamine-mediated β-lactam susceptibility ofA. baumannii. This finding may provide a clue for development of new antimicrobial agents and/or novel strategies to treat multidrug-resistantA. baumannii.

scholarly journals ScoC Regulates Peptide Transport and Sporulation Initiation in Bacillus subtilis

1999 ◽  
Vol 181 (13) ◽  
pp. 4114-4117 ◽  
Author(s):  
Akiko Koide ◽  
Marta Perego ◽  
James A. Hoch
Keyword(s):  
Bacillus Subtilis ◽  
Negative Regulation ◽  
Negative Regulator ◽  
Peptide Transport ◽  
Transport Systems ◽  
Protease Production ◽  
Multicopy Plasmid ◽  
Abc Transport ◽  
Transcription Regulators ◽  
Sporulation Initiation

ABSTRACT Oligopeptides are transported into Bacillus subtilis by two ABC transport systems, App and Opp. Transcription of the operon encoding the Opp system was found to occur during exponential growth, whereas the app operon was induced at the onset of stationary phase. Transcription of both operons was completely curtailed by overproduction of the ScoC regulator from a multicopy plasmid and was enhanced in strains with the scoC locus deleted. ScoC, a member of the MarR family of transcription regulators, is known from previous studies to be a negative regulator of sporulation and of protease production that acts by binding directly to the promoters of the genes it regulates. Since peptide transport is essential for inactivation of the negative regulation of sporulation by Rap phosphatases, the control of ScoC transcription repression activity plays a crucial role in the initiation of sporulation.

scholarly journals Utilization of Oligopeptides by Listeria monocytogenes Scott A

1998 ◽  
Vol 64 (3) ◽  
pp. 1059-1065 ◽  
Author(s):  
Annette Verheul ◽  
Frank M. Rombouts ◽  
Tjakko Abee
Keyword(s):  
Listeria Monocytogenes ◽  
Transport System ◽  
Growth Stimulation ◽  
Sole Source ◽  
Fermented Milk ◽  
Defined Medium ◽  
Peptide Transport ◽  
Transport Systems ◽  
Oligopeptide Transport System ◽  
Oligopeptide Transport

ABSTRACT For effective utilization of peptides, Listeria monocytogenes possesses two different peptide transport systems. The first one is the previously described proton motive force (PMF)-driven di- and tripeptide transport system (A. Verheul, A. Hagting, M.-R. Amezaga, I. R. Booth, F. M. Rombouts, and T. Abee, Appl. Environ. Microbiol. 61:226–233, 1995). The present results reveal that L. monocytogenes possesses an oligopeptide transport system, presumably requiring ATP rather than the PMF as the driving force for translocation. Experiments to determine growth in a defined medium containing peptides of various lengths suggested that the oligopeptide permease transports peptides of up to 8 amino acid residues. Peptidase activities towards several oligopeptides were demonstrated in cell extract from L. monocytogenes, which indicates that upon internalization, the oligopeptides are hydrolyzed to serve as sources of amino acids for growth. The peptide transporters of the nonproteolytic L. monocytogenes might play an important role in foods that harbor indigenous proteinases and/or proteolytic microorganisms, since Pseudomonas fragi as well as Bacillus cereus was found to enhance the growth ofL. monocytogenes to a large extent in a medium in which the milk protein casein was the sole source of nitrogen. In addition, growth stimulation was elicited in this medium when casein was hydrolyzed by using purified protease from Bacillus licheniformis. The possible contribution of the oligopeptide transport system in the establishment of high numbers of L. monocytogenes cells in fermented milk products is discussed.

Roles of the Peptide Transport Systems and Aminopeptidase PepA in Peptide Assimilation by Helicobacter pylori

2015 ◽  
Vol 25 (10) ◽  
pp. 1629-1633 ◽  
Author(s):  
Mi Ran Ki ◽  
Ji Hyun Lee ◽  
Soon Kyu Yun ◽  
Kyung Min Choi ◽  
Se Young Hwang
Keyword(s):  
Helicobacter Pylori ◽  
Peptide Transport ◽  
Transport Systems

Peptide transport systems for opiates across the blood-brain barrier

1990 ◽  
Vol 259 (1) ◽  
pp. E1-E10 ◽  
Author(s):  
W. A. Banks ◽  
A. J. Kastin
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Peptide Transport ◽  
Transport Systems ◽  
Aluminum Stress ◽  
Melanocyte Stimulating Hormone ◽  
Blood Brain ◽  
Opiate Peptides ◽  
The Central Nervous System ◽  
Ethanol Addiction

Opiate peptides administered on one side of the blood-brain barrier can exert powerful effects on processes occurring on the other side. There is evidence for direct passage of opiate peptides and their analogues across this barrier. Beta-Endorphin can enter the cerebrospinal fluid after systemic administration, but its entry into brain tissue has been more difficult to demonstrate, even though analogues enter at a modest rate. Enkephalins enter and exit the central nervous system as intact molecules by a combination of saturable and nonsaturable mechanisms. A family of transport systems may exist with varying affinities for the opiate enkephalins, antiopiates like tyrosine melanocyte-stimulating hormone inhibitory factor 1 (Tyr-MIF-1), and related peptides. The major system transporting these peptides, termed Peptide transport system 1, can be influenced by several factors with entry and exit rates affected by aging, drugs, amino acids, monoamines, aluminum, stress, and ethanol addiction and withdrawal. The homeostatic role of the blood-brain barrier thus extends to the regulation of the bidirectional transport of informational peptides such as the opiates.

scholarly journals The apical (hPepT1) and basolateral peptide transport systems of Caco-2 cells are regulated by AMP-activated protein kinase

2010 ◽  
Vol 299 (1) ◽  
pp. G136-G143 ◽  
Author(s):  
Myrtani Pieri ◽  
Helen C. Christian ◽  
Robert J. Wilkins ◽  
C. A. R. Boyd ◽  
David Meredith
Keyword(s):  
Electron Microscopy ◽  
Protein Kinase ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Glucose Transporter ◽  
Peptide Transport ◽  
Transport Systems ◽  
Immunogold Electron Microscopy ◽  
Glucose Transporter 2 ◽  
Amp Activated Protein Kinase

The effect of 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR) activation of the AMP-activated protein kinase (AMPK) on the transport of the model radiolabeled dipeptide [3H]-D-Phe-L-Gln was investigated in the human epithelial colon cancer cell line Caco-2. Uptake and transepithelial fluxes of [3H]-D-Phe-L-Gln were carried out in differentiated Caco-2 cell monolayers, and hPepT1 and glucose transporter 2 (GLUT2) protein levels were quantified by immunogold electron microscopy. AICAR treatment of Caco-2 cells significantly inhibited apical [3H]-D-Phe-L-Gln uptake, matched by a decrease in brush-border membrane hPepT1 protein but with a concomitant increase in the facilitated glucose transporter GLUT2. A restructuring of the apical brush-border membrane was seen by electron microscopy. The hPepT1-mediated transepithelial (A-to-B) peptide flux across the Caco-2 monolayers showed no significant alteration in AICAR-treated cells. The electrical resistance in the AICAR-treated monolayers was significantly higher compared with control cells. Inhibition of the sodium/hydrogen exchanger 3 (NHE3) had an additive effect to AICAR, suggesting that the AMPK effect is not via NHE3. Fluorescence measurement of intracellular pH showed no reduction in the proton gradient driving PepT1-mediated apical uptake. The reduction in apical hPepT1 protein and dipeptide uptake after AICAR treatment in Caco-2 cells demonstrates a regulatory effect of AMPK on hPepT1, along with an influence on both the microvilli and tight junction structures. The absence of an associated reduction in transepithelial peptide movement implies an additional stimulatory effect of AICAR on the basolateral peptide transport system in these cells. These results provide a link between the hPepT1 transporter and the metabolic state of this model enterocyte.

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