ABSTRACT
Listeria monocytogenes is a food-borne pathogen with a high mortality rate that has also emerged as a paradigm for intracellular parasitism. We present and compare the genome sequences of L. monocytogenes (2,944,528 base pairs) and a nonpathogenic species, L. innocua (3,011,209 base pairs). We found a large number of predicted genes encoding surface and secreted proteins, transporters, and transcriptional regulators, consistent with the ability of both species to adapt to diverse environments. The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events.
Subject(s)
Bacterial Proteins/genetics , Genome, Bacterial , Listeria monocytogenes/genetics , Listeria/genetics , Adaptation, Physiological , Amino Acid Motifs , Bacillus subtilis/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/physiology , Base Composition , Carrier Proteins/chemistry , Carrier Proteins/genetics , Chromosomes, Bacterial/genetics , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Gene Transfer, Horizontal , Genes, Bacterial , Genomics , Listeria/chemistry , Listeria/physiology , Listeria monocytogenes/chemistry , Listeria monocytogenes/pathogenicity , Listeria monocytogenes/physiology , Membrane Proteins/chemistry , Membrane Proteins/genetics , Sequence Analysis, DNA , Staphylococcus aureus/genetics , Transcription Factors/chemistry , Transcription Factors/genetics , Virulence/geneticsABSTRACT
The aim of this study was to characterize the capillary density, progression and persistence of new capillaries induced by different isoforms of vascular endothelial growth factor (VEGF)-A. They were produced and purified using the same protocol and assessed in the same experimental model, the rabbit cornea assay. Monogenic homodimers for VEGF121 and VEGF165 together with the heterodimer VEGF121/165 were tested as slow release polymer pellets implanted into the avascular rabbit cornea and examined up to 18 days post-implantation. The implants consistently stimulated angiogenesis in the absence of inflammation. The VEGF121 isoform produced the strongest increase of new capillary vessels which rapidly and persistently progressed into the corneal stroma. VEGF165 promoted the growth of a smaller number of capillaries which ten-ded to regress over time. Heterodimers of VEGF121/165 produced intermediate in vivo activities between the two homodimers. In vitro endothelial cell proliferation, mobilization and adhesion were promoted by all VEGF isoforms under serum-free or serum-reduced conditions with the same order of potency. Anti-soluble KDR (sKDR) antibody completely inhibited the effects of all the isoforms. These results indicate that monogenic homodimer preparations of VEGF121 and VEGF165 can display distinct biological effects which are functionally retained after the heterodimeric assembly of VEGF121 and VEGF165. The observed different biological behavior of the VEGF isoforms reveals the possibility that in vivo the assembly of dimers derived from splicing of a single gene may yield molecules with either different matrix or receptor interaction, stability or diffusion rate according to specific needs.
