The D-alanyl-d-alanine carboxypeptidase enzyme is essential for virulence in the Schu S4 strain of Francisella tularensis and a dacD mutant is able to provide protection against a pneumonic challenge.

08:00 EDT 9th September 2019 | BioPortfolio

Summary of "The D-alanyl-d-alanine carboxypeptidase enzyme is essential for virulence in the Schu S4 strain of Francisella tularensis and a dacD mutant is able to provide protection against a pneumonic challenge."

Low molecular mass penicillin binding proteins (LMM PBP) are bacterial enzymes involved in the final steps of peptidoglycan biosynthesis. In Escherichia coli, most LMM PBP exhibit dd-carboxypeptidase activity, are not essential for growth in routine laboratory media, and contributions to virulent phenotypes remain largely unknown. The Francisella tularensis Schu S4 genome harbors the dacD gene (FTT_1029), which encodes a LMM PBP with homology to PBP6b of E. coli. Disruption of this locus in the fully virulent Schu S4 strain resulted in a mutant that could not grow in Chamberlain's Defined Medium and exhibited severe morphological defects. Further characterization studies demonstrated that the growth defects of the dacD mutant were pH-dependent, and could be partially restored by growth at neutral pH or fully restored by genetic complementation. Infection of murine macrophage-like cells showed that the Schu S4 dacD mutant is capable of intracellular replication. However, this mutant was attenuated in BALB/c mice following intranasal challenge (LD = 603 CFU) as compared to mice challenged with the parent (LD = 1 CFU) or complemented strain (LD = 1 CFU). Additionally, mice that survived infection with the dacD mutant showed significant protection against subsequent challenge with the parent strain. Collectively, these results indicate that the DacD protein of F. tularensis is essential for growth in low pH environments and virulence in vivo. These results also suggest that a PBP mutant could serve as the basis of a novel, live attenuated vaccine strain.


Journal Details

This article was published in the following journal.

Name: Microbial pathogenesis
ISSN: 1096-1208
Pages: 103742


DeepDyve research library

PubMed Articles [11029 Associated PubMed Articles listed on BioPortfolio]

Inhibition of Pantothenate Synthetase by Analogs of β-Alanine Precursor Ineffective as an Antibacterial Strategy.

Pantothenate, the fundamental precursor to coenzyme A, is required for optimal growth and virulence of microbial pathogens. It is synthesized by the enzyme-catalyzed condensation of β-alanine and pan...

Effect of Glycosaminoglycans on Pathogenic Properties Far-Eastern Tick-Borne Encephalitis Virus.

We studied the effect of sulfated glycosaminoglycan on the infection properties of high-virulence Dal'negorsk strain and low-virulence Primorye-437 of tick-borne encephalitis virus. Differences in rep...

Biochemical characterization and mutational analysis of alanine racemase from Clostridium perfringens.

Clostridium perfringens is a gram-positive, anaerobic, pathogenic bacterium that can cause a wide range of diseases in humans, poultry and agriculturally important livestock. A pyridoxal-5-phosphate-d...

Genome analysis reveals insights into high-resistance and virulence of Salmonella Enteritidis involved in foodborne outbreaks.

Salmonella enterica serovar Enteritidis strain SE86 has been associated with several foodborne diseases occurring in Southern Brazil, becoming and important causative agent of human salmonellosis. In ...

Synthetic microbial consortium with specific roles designated by genetic circuits for cooperative chemical production.

Synthetic microbial consortia consisting of microorganisms with different synthetic genetic circuits or divided synthetic metabolic pathway components can exert functions that are beyond the capacitie...

Clinical Trials [2522 Associated Clinical Trials listed on BioPortfolio]

Clinical Trial of Alanyl-Glutamine or Glycine in Children With Persistent Diarrhea or Malnutrition

This is a double blinded randomized clinical trial of Alanyl-Glutamine or Glycine in children with persistent diarrhea or malnutrition. The primary objective of the study is to determine ...

Carboxypeptidase-G2 in Treating Nervous System Toxic Effects in Patients Given an Overdose of Intrathecal Methotrexate

RATIONALE: Chemoprotective drugs such as carboxypeptidase-G2 may protect normal cells from the toxic effects of chemotherapy. PURPOSE: Clinical trial to study the effectiveness of carboxy...

Effect of β-alanine Supplementation on Muscle Carnosine

Carnosine is a natural acid buffering substance of muscle. The primary objective of this study is to test whether a nutritional supplement of beta-alanine enhances carnosine content in mus...

HIAS II - Study of Nutritional Supplementation in Hospitalized Children With Persistent Diarrhea or Malnutrition

This study will determine the effect of 7 days supplementation of alanyl-glutatime or glycine on the damaged intestinal barrier function on day 8 in children with persistent diarrhea or ma...

β-alanine Supplementation on Knee Extensor Contractile and Force Properties

Carnosine (made by bonding β-alanine and histidine) has been suggested to contribute to the extension of physical exercise, counteracting the decline in muscle performance due to fatigue....

Medical and Biotech [MESH] Definitions

A carboxypeptidase that is specific for proteins that contain two ALANINE residues on their C-terminal. Enzymes in this class play an important role in bacterial CELL WALL biosynthesis.

An NAD-dependent enzyme that catalyzes the reversible DEAMINATION of L-ALANINE to PYRUVATE and AMMONIA. The enzyme is needed for growth when ALANINE is the sole CARBON or NITROGEN source. It may also play a role in CELL WALL synthesis because L-ALANINE is an important constituent of the PEPTIDOGLYCAN layer.

A metallocarboxypeptidase that removes C-terminal lysine and arginine from biologically active peptides and proteins thereby regulating their activity. It is a zinc enzyme with no preference shown for lysine over arginine. Pro-carboxypeptidase U in human plasma is activated by thrombin or plasmin during clotting to form the unstable carboxypeptidase U.

An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC

A ZINC-dependent carboxypeptidase primary found in the DIGESTIVE SYSTEM. The enzyme catalyzes the preferential cleavage of a C-terminal peptidyl-L-lysine or arginine. It was formerly classified as EC and EC

Quick Search

DeepDyve research library

Relevant Topics

Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Searches Linking to this Article