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Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling.

Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodornase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host-pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease.

Animals↗

Association of HL-A 5 and immune responsiveness in vitro to streptococcal antigens.

Lymphocytes, from randomly selected individuals having normal immune function, when incubated in vitro with varying concentrations of streptococcal antigens, responded in three ways: (a) response over the entire antigen concentration range, i.e., responders; (b) low response to only the highest antigen concentrations; and (c) no response at any antigen concentration. Frequency distribution analysis of these groups indicated that a significant association occurred between the ability to respond and HL-A 5.

Adult↗

Inhibition of mitogen- and antigen-induced lymphocyte blastogenesis by herpes simplex virus.

Lymphocytes were separated from peripheral blood of adult human donors by Ficoll-Hypaque gradient centrifugation and cultured in the presence of nonspecific mitogens (phytohemagglutinin[PHA] and concanavalin A) or specific microbial anatigens (herpes simplex virus [HSV], mumps virus, streptococcal enzymes, and Candida albicans). Exposure of lymphocyte cultures to infectious HSV resulted in almost complete inhibition of blastogenesis ([3/H]thymidine uptake) induced by each of the mitogens and antigens, a finding which suggests that a common mechanism may underlie the inhibitory effect. Several characteristics of the effect of virus on blastogenesis were noted: (1) virus inactivated by heat or ultraviolet irradiation was ineffective; (2) inhibition (is greater than 90%) was greatest in cultures exposed to HSV on or before the addition of PHA; (3) lymphocyte preparations washed free of HSV continued to be refractory to stimulation, an observation indicating that the presence of unabsorbed virions or viral products was not essential; and (4) inhibition was independent of the cell donor's state of humoral immunity to HSV.

Antibody Specificity↗

Evaluation of multi skin test in colorectal cancer patients and effects of serum immunosuppressive factor and cytokine production of peripheral mononuclear cells.

Decreased skin reactions using five kinds of recall antigens correlate d with the stage of colorectal cancer. Immunosuppressive factors in the serum (IS index) increased with the progression of the stage in cancer patients, but interleukin (IL)-I and IL-2 production in peripheral mononuclear cells (PBMC) did not correlate with the advance of the disease. In patients with low immunosuppressive factors, the score of skin reactions was significantly higher than that in patients with high immunosuppressive factors. Increased serum immunosuppressive factors seem to reduce skin reactions in the patients. Furthermore, significant difference in skin reaction score was observed between patients with high IL-1 production of PBMC and patients with low IL-1 production of PBMC. These results suggest that skin reaction might be controlled by serum immunosuppressive factors and IL-1 production of PBMC, and that the score of skin reaction using multirecall antigens is a useful parameter to learn the host immunity in colorectal cancer.

Adult↗

Case report. Acute cor pulmonale due to massive pulmonary embolism and successful response to thrombolytic therapy.

The proper place of thrombolytic agents in the management of pulmonary embolism is not yet well defined. A number of survivors of acute massive pulmonary thromboembolism remain in a delicate balance of hemodynamic compensation and where recurrent emboli could frequently be fatal. Successful response to urokinase therapy in such a case is presented and the status of currently available thrombolytic drugs is discussed. We suggest that thrombolytic therapy in massive pulmonary embolism would provide greater hemodynamic reserve, alleviate shock, minimize the chances of recurrent emboli and prevent permanent impairment to the pulmonary vascular bed.

Fibrinolytic Agents↗

Delayed cutaneous hypersensitivity testing.

The topic of delayed cutaneous hypersensitivity testing is reviewed. When skin tests are used to determine whether an individual is anergic, T cell immunity is evaluated. Skin testing can be used to determine the causative organisms of infection or to discover an immunologic deficiency state. Characteristic skin lesions usually develop after intradermal injection of the antigen. Skin testing uses the most ubiquitous environmental antigens and those that are safe, cheap, and effective. Important issues dealing with skin tests include false-positive and false-negative reactions, which antigens to use in an antigen "battery," their lack of standardization, and the method of administration. Despite the problems, skin testing remains an easy, relatively safe method of assessing the immune system. Some investigators are developing more reliable testing methods and alternative antigens. Further research is needed to develop a reliable method for assessing delayed cutaneous hypersensitivity.

Antigens, Fungal↗