Impact of Bacterial Toxins in the Lungs

Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate lung barrier function and to impair host defense in order to promote infection. Although in general, these toxins target common cellular signaling pathways and host compartments, toxin- and cell-specific effects have also been reported. Toxins can affect resident pulmonary cells involved in alveolar fluid clearance (AFC) and barrier function through impairing vectorial Na$^{+}$ transport and through cytoskeletal collapse, as such, destroying cell-cell adhesions. The resulting loss of alveolar-capillary barrier integrity and fluid clearance capacity will induce capillary leak and foster edema formation, which will in turn impair gas exchange and endanger the survival of the host. Toxins modulate or neutralize protective host cell mechanisms of both the innate and adaptive immunity response during chronic infection. In particular, toxins can either recruit or kill central players of the lung's innate immune responses to pathogenic attacks, i.e., alveolar macrophages (AMs) and neutrophils. Pulmonary disorders resulting from these toxin actions include, e.g., acute lung injury (ALI), the acute respiratory syndrome (ARDS), and severe pneumonia. When acute infection converts to persistence, i.e., colonization and chronic infection, lung diseases, such as bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) can arise. The aim of this review is to discuss the impact of bacterial toxins in the lungs and the resulting outcomes for pathogenesis, their roles in promoting bacterial dissemination, and bacterial survival in disease progression

Pneumococcal vaccines: mechanism of action, impact on epidemiology and adaption of the species

Abstract Pneumococcal infections elicited by Streptococcus pneumoniae (pneumococcus) (pneumonia, otitis media, sinusitis, meningitis) are frequently occurring diseases that are associated with considerable morbidity and mortality even in developed countries. Pneumococci colonise the nasopharynx of up to 50% of children, and up to 5% of adults are pneumococcal carriers. Two pneumococcal vaccines are currently in clinical use. One of them contains 23 capsular polysaccharides of the as yet known 91 different pneumococcal serotypes. Because polysaccharide vaccines primarily induce a B-cell-dependent immune response, this type of vaccine prevents bacteraemia but does not efficiently protect the host against pneumococcal infection. In 2000, a vaccination programme was launched in the USA making use of a novel pneumococcal conjugate vaccine containing capsular polysaccharides derived from the seven most frequent pneumococcal serotypes causing pneumococcal disease in children <2 years of age. Conjugation of capsular polysaccharides with a highly immunogenic protein, i.e. a non-toxic diphtheria toxoid, induces a B-and T-cell response resulting in mucosal immunity and thus effectively protects against vaccine serotypes that induce invasive pneumococcal disease, thereby at the same time reducing vaccine serotype carrier rates. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as reduced antibiotic resistance rates. However, recent studies report that serotypes eradicated by the vaccine are being replaced by non-vaccine pneumococcal serotypes. This so-called 'replacement' might soon threaten the success of vaccine use