Lewis Lab Research


The Lewis lab is interested in the roles played by the female urogenital microbiota and its members in urinary and reproductive health and disease. We build novel model systems to interrogate mechanisms of host-microbe interactions within the complex ecological and immunological niches of the female urogenital tract. In particular, our studies seek to define the contributions of individual organisms to disease processes that are thought to be polymicrobial, to understand whether and how mucosal carriage states of potential pathogens may influence host susceptibility to infection, and to better understand how biochemical processes occurring at the community level influence the development of disease states. We have made great progress in these areas recently. One of our projects seeks to understand the role of the vaginal microbiota and its members in women’s susceptibility to urinary tract infection (UTI). Recently we have provided proof of principal that the composition of bacterial exposures to the urinary tract can in fact influence the outcome of UTI. Another area of interest in the lab is the polymicrobial imbalance of the vaginal microbiota known as bacterial vaginosis (BV). We were the first group to successfully apply Koch's postulates to BV, showing that Gardnerella vaginalis is sufficient to cause many of the clinical features of the condition. We have also demonstrated G. vaginalis as the first example of a mucus-degrading BV-associated bacterium, showing that the organism not only degrades mucus components; but, in fact depletes the vaginal mucosa of molecules that have important protective functions. Mucus degradation is thought to be an important virulence determinant that may explain why women with BV are at greater risk of intrauterine infections, preterm birth, and increased risk of other genitourinary infections including HIV, Chlamydia, Gonorrhea, urinary tract infection, and pelvic inflammatory disease. Our ongoing research employs principles in molecular and medical microbiology, bacterial genetics, biochemistry, and clinical outcomes-based research to understand specific functions of the vaginal microbiota in health and disease and to translate these advances in understanding to improve the health of women and infants.

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PUBLICATIONS


  1. Lewis, A.L.; Nizet, V.; Varki. A.  2004. Discovery and Characterization of Sialic Acid O-Acetylation in Group B Streptococcus. Proc. Nat. Acad. Sci. U.S.A. 101(30): 11123-11128
  2.  Hayakawa, T.; Angata,T.; Lewis, A.L.; Mikkelsen, T.; Varki, N.; Varki, A. 2005 A human-specific gene in microglia. Science 309 (5741):1693.
  3.  Lewis, A. L.; Altheide, T.K.; Varki, A.; Arden, K.; Varki, N.M. 2005. Combining Parenting and a Science Career. Science 307(5716): 1720.
  4. Lewis, A.L.; Hensler, M.; Nizet, V; Varki, A. 2006. The group B streptococcal sialic acid O-acetyltransferase is encoded by neuD, a conserved component of bacterial sialic acid biosynthetic gene clusters. J Biol Chem.  281(16):11186.
  5. Carlin, A.F.; Lewis, A.L.; Varki, A.; Nizet, V. 2007. Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin-like lectins) on human leukocytes.J Bacteriol. 189(4):1231-7.
  6. Lewis, A.L.; Cao, H.; Patel, S.K.; Diaz, S.; Ryan, W.; Carlin, A.F.; Thon, V.; Lewis, W.G.; Varki, A.; Chen, X.; Nizet, V. 2007. NeuA sialic acid O-acetylesterase activity modulates O-acetylation of capsular polysaccharide in Group B Streptococcus. J. Biol. Chem. 282 (38):27562-71.
  7. Carlin, A.; Uchiyama, S.; Chang, Y.; Lewis, A.L.; Nizet, V.; Varki, A. 2009. Molecular Mimicry of Host Sialylated Glycans Allows a Bacterial Pathogen to Engage Neutrophil Siglec-9 and Dampen the Innate Immune Response. Blood. 113(14):3333-6.
  8. Pannaraj PS, Edwards MS, Ewing KT, Lewis AL, Rench MA, Baker CJ. 2009. Group B streptococcal conjugate vaccines elicit functional antibodies independent of strain O-acetylation. Vaccine.16;27 (33):4452-6.
  9. Lewis, A.L.; Varki, A. Evolutionary Considerations in Studying the Sialome: Sialic Acids and the Host-Pathogen Interface. Bioinformatics for Glycobiology and Glycomics: An Introduction.  pgs 69-88. Wiley & Sons Ltd. 2009.
  10. Weiman S, Dahesh S, Carlin AF, Varki A, Nizet V, Lewis AL. 2009. Genetic and Biochemical Modulation of Sialic Acid O-Acetylation on Group B Streptococcus: Phenotypic and Functional Impact. Glycobiology. (11):1204-13.
  11. Lewis, A.L.; Desa, N.; Hansen, E.E.; Knirel, Y.; Gordon, J.; Gagneux, P.; Nizet, V.; Varki, A. 2009. Innovations in Host and Microbial Sialic Acid Biosynthesis Revealed by Phylogenomic Prediction of Nonulosonic Acid StructureProc. Natl. Acad. Sci. U S A. 11;106 (32):13552-7.
  12. Weiman S, Uchiyama S, Lin FY, Chaffin D, Varki A, Nizet V, Lewis AL. 2010. O-Acetylation of Sialic Acid on Group B Streptococcus Inhibits Neutrophil Suppression and Virulence. Biochem J. 428(2):163-8.
  13. Lewis, A.L.; Lubin, J.B.; Argade, S.; Naidu, N.; Choudhury, B.; and Boyd, E.F. 2011. Genomic and Metabolic Profiling of Nonulosonic Acids in Vibrionaceae reveal Biochemical Phenotypes of Allelic Divergence in V. vulnificus Appl. Environ. Microbiol. Aug;77(16):5782-93. PMID: 21724895
  14. Kline, K.A.; Schwartz, D.J.; Lewis, W.G.; Hultgren, S.J.; Lewis, A.L. 2011. Immune Activation and Suppression by Group B Streptococcus in a Murine Model of Urinary Tract Infection. Infect Immun. Sep;79(9):3588-95. PMID: 21690238
  15. Lewis, WG; Robinson, LS; Perry, JC; Bick, JL; Peipert, JF; Allsworth, JE; Lewis, AL. 2012. Hydrolysis of Secreted Immunoglobulin A (IgA) in ex Vivo and Biochemical Models of Bacterial Vaginosis. J Biol Chem. 287(3): 2079-89. PMID: 22134918
  16. Lewis AL, Lewis WG. 2012. Host Sialoglycans and Bacterial Sialidases: A Mucosal Perspective. Cell Microbiol. 2012 14(8):1174-82. PMID: 22519819
  17. Ricaldi,JN; Matthias, MA; Vinetz, JM; Lewis, AL. 2012 Expression of Sialic Acids and other Nonulosonic Acids in Leptospira. BMC Microbiol. 12 (1):161. PMID: 22853805
  18. Kline, K.A.; Schwartz, D.J.; Gilbert, NM; Hultgren, S.J.; Lewis, A.L. Immune Modulation by Group B Streptococcus  Influences Host Susceptibility to Urinary Tract Infection by Uropathogenic E. coli  Infect. Immun. 2012 Sept 17. [Epub ahead of print] PMID 22988014
  19. Lewis, WG; Robinson, LS; Gilbert, NM; Lewis, AL. Degradation, Foraging, and Depletion of Mucus Sialoglycans by the Vaginal-Adapted Actinobacterium Gardnerella vaginalis. J Biol Chem. 2013 Mar 11. [Epub ahead of print]. PMID: 23479734
  20. Gilbert, NM; Lewis, WG; Robinson, LS;  Lewis, AL. Clinical Features of Bacterial Vaginosis in a Murine Model of Vaginal Infection withGardnerella vaginalis. PLoS One. 2013;8(3):e59539. doi: 10.1371/journal.pone.0059539. Epub 2013 Mar 19. PMID: 23527214 
  21. Gilbert N.M.; O’Brien, V.; Lewis W.G.; Hultgren, S.J.; Macones, G.; Lewis A.L.Urinary Tract Infection as a Preventable Cause of Pregnancy Complications: Opportunities, Challenges, and A Global Call to Action. Global Advances in Health and Medicine (in press)