Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models

Streptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. We examined adaptation and evolution of pneumococcus, within nasopharynx and lungs, in an experimental system where the selective pressures associated with transmission were removed. This was achieved by serial passage of pneumococci, separately, in mouse models of nasopharyngeal carriage or pneumonia. Passaged pneumococci became more effective colonizers of the respiratory tract and we observed several examples of potential parallel evolution. The cell wall-modifying glycosyltransferase LafA was under strong selection during lung passage, whereas the surface expressed pneumococcal vaccine antigen gene pvaA and the glycerol-3-phosphate dehydrogenase gene gpsA were frequent targets of mutation in nasopharynx-passaged pneumococci. These mutations were not identified in pneumococci that were separately evolved by serial passage on laboratory agar. We focused on gpsA, in which the same single nucleotide polymorphism arose in two independently evolved nasopharynx-passaged lineages. We describe a new role for this gene in nasopharyngeal carriage and show that the identified single nucleotide change confers resistance to oxidative stress and enhanced nasopharyngeal colonization potential. We demonstrate that polymorphisms in gpsA arise and are retained during human colonization. These findings highlight how within-host environmental conditions can determine trajectories of bacterial evolution. Relative invasiveness or attack rate of pneumococcal lineages may be defined by genes that make niche-specific contributions to bacterial fitness. Experimental evolution in animal infection models is a powerful tool to investigate the relative roles played by pathogen virulence and colonization factors within different host niches.     

Immunologic responses in patients with pulmonary carcinoma receiving immunotherapy

Summary This is a preliminary report on immune responses observed in vivo and in vitro in resectable patients treated with oral BCG, and in nonresectable patients treated with autologous tumour cells complexed with PPD and with BCG applied by scarification. In some cases, to shorten the period of sensitization, transfer factor was given additionally. Several of the in vitro methods used for assessing the immune competence of the patients are shown to be sufficiently informative to warrant their use before immunotherapy in order to assess the immunologic resources of the patient. During immunotherapy, they allow monitoring the effect of the treatment.     

Studies on ulcerative dermal necrosis of salmonids

The skin of the head of adult Atlantic salmon S. solar L. was examined by light and electron microscopy. The general structure resembled that of most other vertebrates, but in common with other fish, the melanocytes were restricted to the papillary layer of the dermis. The mucus secreting cells were shown to elaborate a series of separate membrane bound vesicles of secretion. The basement-membrane was complex, with a system of primary, and secondary micro-papillae showing close adherence to the bases of the epithelial cells, which were modified to form a thick, electron dense basal plasma membrane. No evidence to suggest a reason for the localization of the early lesions of ulcerative dermal necrosis to specific areas of the epithelium of the head was adduced.