Assistant Professor Chris Sham

Chris Sham

PhD

Assistant Professor

Department of Microbiology and Immunology

Email: miclts@nus.edu.sg

Lab: Dr. Sham's lab

Research Interest

Streptococcus pneumoniae

Streptococcus pneumoniae is an important respiratory pathogen that causes more than two million deaths worldwide annually. Similar to many pathogenic bacteria, S. pneumoniae, encases its cell envelope with capsular polysaccharide (CPS), which protects it from opsonophagocytosis and mucus clearance. Because of its importance in pathogenesis, all clinically relevant vaccines against S. pneumoniae target the CPS. There are over 90 serotypes identified in S. pneumoniae. The structural variance in CPS produced is attributed to the extreme diversity of enzymes located in the cps locus. Although these enzymes were identified decades ago, little is known about the molecular mechanisms governing their specificity, regulation, and function. Therefore, the long-term goal of our research program is to address this knowledge gap by investigating how specificity is determined for CPS enzymes.

Current Projects

  • High-throughput identification of new factors require for CPS biogenesis
  • Investigate the mechanisms of CPS precursor assembly
  • Investigate the mechanism of polysaccharide flipping by MOP-family flippases
  • Pathway-directed chemical screening for small molecule inhibitors that disrupt CPS biogenesis

Recent Publications

  1. Chamakura KR, Sham LT, Davis RM, Min L, Cho H, Ruiz N, Bernhardt TG, Young R (2017). A viral protein antibiotic inhibits lipid II flippase activity. Nature Microbiology, 2:1480-84.
  2. Meeske AJ, Sham LT, Kimsey H, Koo BM, Gross CA, Bernhardt TG, Rudner DZ. 2015. MurJ and a novel lipid II flippase are required for cell wall biogenesis in Bacillus subtilis. PNAS. 112:6437-42.
  3. Sham LT, Butler EK, Lebar MD, Kahne D, Bernhardt TG, Ruiz N. 2014. Bacterial cell wall. MurJ is the flippase of lipid-linked precursors of peptidoglycan biogenesis. Science. 345:220-2.
  4. Sham LT, Jensen KR, Bruce KE, Winkler ME. 2013. Involvement of FtsE ATPase and FtsX extracellular loops 1 and 2 in FtsEX-PcsB complex function in cell division of Streptococcus pneumoniae D39. mBio. 16:e00431-13.
  5. Kocaoglu O, Calvo RA, Sham LT, Cozy LM, Francis S, Lanning BR, Winkler ME, Kearns DB, Carlson EE. 2012. Selective penicillin binding protein imaging probes reveal substructure in bacterial cell division. ACS Chem Biol. 7:1746-53.
  6. Sham LT, Tsui HCT, Land AD, Barendt SM, Winkler ME. 2011. Recent advances in pneumococcal peptidoglycan biosynthesis suggest vaccine and antimicrobial targets. Curr Opin Microbiol. 15: 194-203.
  7. Sham LT, Barendt SM, Kopecky KE, Winkler ME. 2011. Essential PcsB putative peptidoglycan hydrolase interacts with the essential FtsXSpn cell division protein in Streptococcus pneumoniae. PNAS. 108:E1061-1069.
  8. Barendt SM, Sham LT, Winkler ME. 2011. Characterization of mutants deficient in the L,D-carboxypeptidase (DacB) and WalRKSpn (VicRK) regulon involved in peptidoglycan maturation of Streptococcus pneumoniae serotype 2 strain D39. J Bacteriol, 193: 2290-2300.
  9. Barendt SM, Land AD, Sham LT, Ng WL, Tsui HC, Arnold RJ, Winkler ME. 2009. Influences of capsule on cell shape and chain formation of wild-type and pcsB mutants of serotype 2 Streptococcus pneumoniae. J Bacteriol, 191: 3024-3040.
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