117 Review Article From the Section of Infection, Departments of Medicine, Taipei Medical University - Wan Fang Hospital, Taipei, Taiwan; 1 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan. Received: Mar. 6, 2007; Accepted: Aug. 2, 2007 Correspondence to: Dr. Li-Min Huang, Department of Pediatrics, National Taiwan University Hospital. 7, Jhongshan S. Rd., Jhongjheng District, Taipei City 100, Taiwan (R.O.C.) Tel.: 886-2-23123456 ext. 5139; Fax: 886-2-23934749; E-mail: lmhuang@ha.mc.ntu.edu.tw The Transforming Streptococcus Pneumoniae in the 21st Century Yu-Chia Hsieh, MD, PhD; Wen-Sen Lee, MD; Pei-Lan Shao 1 , MD; Luan-Yin Chang 1 , MD, PhD; Li-Min Huang 1 , MD, PhD Streptococcus pneumoniae, an important pathogen causing sepsis, sinusitis, otitis media, bacterial meningitis and bacterial pneumonia, results in global morbidity and mortality each year. The burden of pneumococcal disease is highest in chil- dren and the elderly. Treatment of pneumococcal infection has been hampered by the complexity of the host immune response. In recent decades, the increase of S. pneumoniae strains’ resistance to β-lactam antibiotics and other classes of antimicrobials has made treatment even more complicated. Fortunately, the advent of heptavalent conjugate vaccine con- fers a high degree of protection against pneumococcal disease and colonization caused by vaccine serotype strains. After the introduction of conjugate pneumococcal vaccine, invasive pneumococcal disease caused by vaccine serotypes and antibi- otic-resistant isolates has been reduced. However, naturally transformable pneumococci may escape vaccine-induced immunity by switching their cap- sular genes to non-vaccine serotypes. Development of cheaper, serotype-independent vac- cines based on a combination of protein antigens should be pursued. (Chang Gung Med J 2008;31:117-24) Key words: Streptococcus pneumoniae, conjugate vaccine, transformable S treptococcus pneumoniae, a pathogen discovered more than one hundred years ago, remains a lead- ing cause of bacteremia, sinusitis, otitis media, bac- terial meningitis and pneumonia. This bacterium is present worldwide, and is associated with substantial illnesses and deaths in humans. (1) Historically, study of the biology of S. pneumoniae led to the identifica- tion of the nature of genetic material, the phenome- non of quorum sensing, the use of polysaccharide- based vaccine and the recognition of bacterial resis- tance to antimicrobial drugs. (2,3) Since the complete genome of S. pneumoniae was decoded in 1997, much has been discovered about the bacterial pro- teins involved in pneumococcal disease, the regula- tion of virulence and the regulation of DNA uptake. (4) Recently, the landscape of pneumococcal infection has been changed by two major events, namely, availability of conjugate pneumococcal vaccine and more aggressive behavior of pneumococcal pneumo- nia. (5,6) It is now a good time to review our under- Dr. Li-Min Huang