The Streptococci make up a medically important genera of microbes known to cause several types of disease in humans, including, for example, otitis media, conjunctivitis, pneumonia, bacteremia, meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid. Since its isolation more than 100 years ago, Streptococcus pneumoniae has been one of the more intensively studied microbes. For example, much of our early understanding that DNA is, in fact, the genetic material was predicated on the work of Griffith and of Avery, Macleod and McCarty using this microbe. Despite the vast amount of research with S. pneumoniae, many questions concerning the virulence of this microbe remain. It is particularly preferred to employ Streptococcal genes and gene products as targets for the development of antibiotics.
The frequency of Streptococcus pneumoniae infections has risen dramatically in the past 20 years. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate Streptococcus pneumoniae strains which are resistant to some or all of the standard antibiotics. This has created a demand for both new anti-microbial agents and diagnostic tests for this organism.
Several species of gram-positive pathogenic bacteria express cell wall proteins that bind to the Fc region of IgA in humans. Two of these from Streptococcus have been studied in detail: protein Arp from the group A Streptococcus and protein Bac from the group B Streptococcus (see Lindahl, G., Akerstrom, B., Stenberg, L., Frithz, E and Heden, L. O. (1991) in Genetics and Molecular Biology of Streptococci, Lactococci and Enterococci (Dunni, G M et al., eds.) pp 155-159, American Soc. Microbiol. and also Jerlstrom, P. G., Chhatwal, G. S. and Timmis, K. N. (1991) Mol. Microbiol. 5: 843). Such proteins are valuable as immunochemical tools as it is likely that they are used by the bacteria to evade the defense mechanisms of the infected host (see Stenberg L., et al. (1994) J.Biol.Chem. 269(18): 13458).
Clearly, there is a need for factors, such as the compounds of the invention, that have a present benefit of being useful to screen compounds for antibiotic activity. Such factors are also useful to determine their role in pathogenesis of infection, dysfunction and disease. There is also a need for identification and characterization of such factors and their antagonists and agonists which can play a role in preventing, ameliorating or correcting infections, dysfunctions or diseases.
The polypeptides of the invention have amino acid sequence homology to a known Streptococcus agalactiae IgA Fc binding protein protein.
USPTO Backgrounds
USPTO Backgrounds