PLEIOTROPIC MUTATIONS ALTER THE KINETICS OF CALCIUM-TRANSPORT, COMPETENCE REGULATION, AUTOLYSIS AND EXPERIMENTAL VIRULENCE IN STREPTOCOCCUS-PNEUMONIAE

Citation
E. Azoulaydupuis et al., PLEIOTROPIC MUTATIONS ALTER THE KINETICS OF CALCIUM-TRANSPORT, COMPETENCE REGULATION, AUTOLYSIS AND EXPERIMENTAL VIRULENCE IN STREPTOCOCCUS-PNEUMONIAE, Research in microbiology, 149(1), 1998, pp. 5-13
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Microbiology
Journal title
ISSN journal
0923-2508
Volume
149
Issue
1
Year of publication
1998
Pages
5 - 13
Database
ISI
SICI code
0923-2508(1998)149:1<5:PMATKO>2.0.ZU;2-N
Abstract
Streptococcus pneumoniae is a pathogen in which the extracellular calc ium concentration plays a major physiological role, in growth as well as in the induction of competence for genetic transformation and activ ation of autolysis. Both responses are under the control of a protein activator exported in the medium. We have checked the impact of mutati ons which alter the regulation of competence and autolysis on experime ntal virulence. Isogenic encapsulated derivatives carrying the relevan t mutations were serotype 3 smooth clones, obtained by transformation of the relevant rough strains with DNA from a serotype 3 smooth isolat e. Survival kinetics and bacterial clearance from the blood were follo wed after intraperitoneal infection of Swiss mice with the different b acterial cultures. In this model, mutants showing an attenuation of vi rulence relative to the wild type fell into two classes. In the first, represented by the lytA::ery mutant V1095 defective for calcium-induc ed autolysis, attenuated virulence could be correlated with rapid bact erial clearance from the blood. In the second, represented by the dmb mutants V2200 and V3300, attenuation was associated with delayed bacte rial clearance from the blood, and correlated with altered kinetics of calcium transport and of regulation of competence and autolysis. It a ppeared unlikely that attenuation of virulence for strains V2200 and V 3300 was a direct consequence of their competence phenotype, since the com::ery mutants V1008 and V1019, defective for the production of the competence activator, were as virulent as the wild-type strain. Autol ysis involving an N-acetyl-muramyl-alanine amidase encoded by lytA was also regulated by calcium. The inserted allele lytA0::ery further red uced virulence in the dmb1 background (V2200). This additive effect of lytA(-) to dmb1 points to different routes of virulence regulation by LYT and DMB1 and suggests that the kinetics of calcium traffic contro ls several pathways involved in the virulence of pneumococcus.