Third, because the virulence of Salmonella species is multifactorial, the choice of model system is crucial. For example, S typhimurium in the mouse is equivalent to Salmonella typhi in humans and, therefore, is not the best model for localized gastroenteritic infections caused by Salmonella species in humans. The rabbit ileal loop model and the in vitro organ culture system derived from it were chosen for a laboratory animal model for human disease caused by Salmonella species based on the work of Giannella and colleagues in the 1970s. But, if Caco-2 cells (which are gut-derived, tight junction-forming, microvilli-expressing cells) are used as model epithelia, the tight junction cleavage by Salmonella serotype dublin cannot be demonstrated, as was shown in vivo. buy asthma inhaler
Fourth, the question of the number, nature and role of Salmonella toxins is still generally confusing. However, the histotoxin described above has been demonstrated to produce the same lesion in vivo and in vitro. In contrast, there is little evidence to implicate a CT-like enterotoxin in the causation of Salmonella-induced diarrhea in experimental infections of rabbits or in calves.
Fifth, with virulent strains, fluid secretion was always accompanied by a massive influx of polymorphonuclear (PMN) cells. However, PMN influx per se was not sufficient to cause fluid secretion. Finally, based on limited experimental data, the ability of nonhistotoxic Salmonella to induce fluid secretion was greater than histotoxic Salmonella. It appears that it is the nature of the damage rather than the mere extent of the damage that determines the severity of the diarrheal response. As in an increasing number of areas in infectious disease, it is becoming clear that cytokines play an important but as yet unclarified role in the pathophysiological response leading to diarrhea.
In recent years, there has been a huge effort, still actively ongoing, to discover the molecular genetic basis of virulence of Salmonella. As a result, at least five ‘pathogenicity islands’ have been recognized in the Salmonella chromosome. For general reviews on this fast moving topic. It is beyond the scope of this review, and somewhat premature because the field is rapidly developing, to attempt a detailed coverage of this complex field in relation to Salmonella species, but a few emerging points are summarized. First, the genes recognized in these Salmonella pathogenicity island (SPI) clusters are mainly involved with invasion of eukaryotic cells, intracellular survival and systemic infection. Second, at least SPI-1 and SPI-2 are known to encode type III secretion systems. Some of the secreted proteins have been recognized and are involved in the translocation of effector molecules into eukaryotic target cells, thereby promoting invasion. Appendage structures have been observed whereby S typhimurium attaches to gut epithelia. These appendages are remarkably similar to those described for EPEC but have not yet been fully characterized. It is only a matter of time before the Salmonella picture is developed to a similar extent as that already described above for EPEC and EHEC.