Mice were infected intranasally with a serotype 2 pneumococcus, a pneumolysin-negative derivative (PLN-A), or an autolysin-negative derivative (AL-2). Numbers of wild type pneumococci were seen in the lung from approximately 12 h after infection and were first detected in the blood around this time. Immunofluorescent staining of lung sections showed that pneumolysin was produced in vivo. Pneumococcal infection resulted in alteration of the composition of the blood but not the bone marrow. Some of the hematologic changes did not occur after PLN-A. PLN-A had a slower growth rate in the lung and bacteremia was delayed. AL-2 was rapidly cleared from the lungs and was not detected in the blood. These events paralleled the pattern of histology in the lung, with the severity of inflammation reduced with PLN-A and no inflammation or hematologic changes with AL-2.

In eukaryotic cells, variations in the levels of cytosolic free calcium regulate processes as important and disparate as chemotaxis, chromosome segregation, fertilization, ion transport, muscle contraction, passage through cell cycle transition points, proteolysis, secretion, and substrate uptake (7). Cytosolic free calcium concentration is tightly controlled by the action of specific pumps and channels in the plasma membrane and subcellular organelles (8,83). Response to increased cytosolic free calcium concentration is mediated by either direct binding to calcium-sensitive enzymes, such as protein kinase C (49) and calpain (72), or activation of a protein transducer, such as calmodulin (15).In prokaryotic cells, an equivalent important role for calcium has been harder to demonstrate but is now becoming evident (53,59,69). Research on a variety of bacterial processes has passed from the phase of demonstrating a likely involvement of calcium to clarifying the nature of this involvement. In this minireview, recent evidence on the existence of bacterial components (both proteinaceous and nonproteinaceous) concerned with calcium regulation is evaluated, since investigation of these components is one of the surest routes to confirming the involvement of calcium in a process. These components include voltage-gated calcium channels responsible for influx that can be formed from poly-3-hydroxybutyratepolyphosphate complexes, primary and secondary transporters responsible for efflux, and calmodulin-like proteins responsible for mediating responses to calcium. Such calcium-dependent regulation may be exerted directly by changes in nucleoid structure or indirectly by phosphorylation or proteolysis of target proteins. Despite the problems sometimes associated with studies of calcium, this ion is increasingly implicated in a number of bacterial functions, including heat shock, pathogenicity, chemotaxis, differentiation, and the cell cycle. INTRACELLULAR CALCIUM LEVELSEstimates of the intracellular free calcium concentration of 0.1 and 1 M in the model organism Escherichia coli have been obtained with Fura-2 {1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran -5 -oxy] -2-(2Ј -amino -5Ј -methylphenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid} (24, 77) and aequorin (85), respectively. Such levels are similar to those in eukaryotic cells and are a 1,000 times less than those typically found outside the cell. Three factors are considered responsible for this low level: the low permeability of the envelope with tightly controlled influx mechanisms, a high buffering capacity, and effective export systems. CALCIUM INFLUXIn eukaryotic cells, a number of mechanisms for gated entry of calcium have been characterized. Families of calcium channels have been identified, which can be classified broadly by the stimulus for channel opening into voltage-operated, receptoroperated, mechanically operated or tonically active calcium channels (83). In particular, eukaryotic L-type, voltage-operated calcium channels (VOCCs) are activated by membrane depolari...

SummaryCopper/zinc-cofactored superoxide dismutase ([Cu,Zn]-SOD) has been found in the periplasm of many bacterial species but its biological function is unknown. Here we report the cloning and characterization of sodC, encoding [Cu,Zn]-SOD, from Salmonella typhimurium. The predicted protein sequence shows only 58% identity to Escherichia coli SodC, and from this its chromosomal location and its immediate proximity to a phage gene, sodC, in Salmonella is speculated to have been acquired by bacteriophagemediated horizontal transfer from an unknown donor. A sodC mutant of S. typhimurium was unimpaired on aerobic growth in rich medium but showed enhanced sensitivity in vitro to the microbicidal action of superoxide. S. typhimurium, S. choleraesuis and S. dublin sodC mutants showed reduced lethality in a mouse model of oral infection and persisted in significantly lower numbers in livers and spleens after intraperitoneal infection, suggesting that [Cu,Zn]-SOD plays a role in pathogenicity, protecting Salmonella against oxygen radical-mediated host defences. There was, however, no observable difference compared with wild type in the interaction of sodC mutants with porcine pleural, mouse peritoneal or J774 macrophages in vitro, perhaps reflecting the hierarchical capacity of different macrophage lines to kill Salmonella, the most efficient overwhelming the proposed protective effect of periplasmic SOD.

Prolongation of activated partial thromboplastin time in streptococcal toxic shock syndrome is associated with activation of the contact system, possibly contributing to the profound shock associated with streptococcal toxic shock syndrome.