Abstract
Introduction
Integral to the survival of a bacterium is the ability to sense and respond to its environment. This can have huge significance in infection processes through the regulation of virulence factors, such as Bacillus anthracis spore germination and virulence gene expression in response to phagocytosis by alveolar macrophages (Guidi-Rontani, 2002).
Two-component systems (TCSs), also referred to as two-component signal transduction systems, are recognized as a key mechanism through which bacteria perceive and respond to their environment. Here we discuss the significant advances that have been made in the understanding of TCSs in Streptococcus pneumoniae (the pneumococcus), in particular with regards to the role of these systems in the virulence of this important human pathogen.
The pneumococcus
With the exception of atypical equine isolates (Whatmore et al., 1999), S. pneumoniae is normally found as a harmless commensal of the human upper respiratory tract. However, depending on host and bacterial factors that are not fully understood, the pneumococcus is also a major cause of diseases such as pneumonia, meningitis, septicaemia, bronchitis and otitis media. An illustration of its significance as a pathogen comes from the estimate that S. pneumoniae causes the death of 1 million young children per year in developing countries (Mulholland, 1997). Its impact, however, is also significant in the developed world; for example, in the USA the pneumococcus is responsible for 50 000 cases of pneumonia, 3000 cases of meningitis and 7 million cases of otitis media annually (Obaro, 2000). Furthermore, inadequate diagnosis, especially in the developing world, is suspected to underestimate the true burden imposed by pneumococcal disease. Current vaccines based on the pneumococcal polysaccharide capsule have significant disadvantages (Bogaert et al., 2004). In the case of purified polysaccharides, these are poorly immunogenic in children under 2 years old, an age group that suffers a high incidence of pneumococcal disease. Conjugate vaccines with purified capsular polysaccharide conjugated to a protein carrier resolve this problem. However, conjugate vaccines are beset by high production costs and limited coverage of pneumococcal serotypes, of which 90 are known. Adding to concerns over pneumococcal disease is the increase and spread of antibiotic resistance (Tan, 2003). Renewed efforts are now being made to understand the pathogenesis of pneumococcal disease with TCSs receiving much attention of late.