Lewis Lab Research

Carbohydrate molecules adorn the surfaces of all cells and influence a wide variety of biological phenomena, including host-microbe interactions. My lab integrates bacterial genetic systems, analytical approaches in biochemistry and glycobiology, phylogenetics, cellular and animal models of infection, and clinical specimens to investigate how bacterial surface sugars, their modifications, and their degradation impact microbial ecology and host-microbe interactions. We aim to gain fundamental biological insights about the roles of bacterial sugars in niche establishment and pathogenesis and harness this information to treat infections in susceptible populations.

My lab specializes in the study of a unique class of nine-carbon backbone monosaccharides called sialic acids. Sialic acids have prominent terminal positions and vital physiological functions on all mammalian cells. On the host, sialic acids regulate processes such as lymphocyte activation, neuronal plasticity, and renal filtration through a variety of mechanisms. Sias are also found on some bacterial pathogens, where they facilitate evasion of multiple innate immune clearance mechanisms by engagement (and hijacking) of host Sia-binding receptors. Microorganisms that express sialic acids at high densities are capable of serious systemic illnesses due to their ability to subvert the complement system and thus proliferate in the bloodstream. Other microbes express enzymes that specifically degrade sialic acids, often in concert with transport and metabolic pathways that allow consumption of the liberated monosaccharides. My lab explores biological processes related to the evolution, expression, modification, and degradation of bacterial and host sialic acids during host colonization and infection. In particular, we are interested in how the ecology of host and microbial sialic acids influences host immune status in the female urogenital tract.

Selected Publications:

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

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.

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.

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.

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 Structure. Proc. Natl. Acad. Sci. U S A. 11;106(32):13552-7.

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.

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.

Lewis, A.L.; Lubin, J.B.; Almagro-Moreno, S.; Argade, S.; Naidu, N.; Choudhury, B.; and Boyd, E.F. Genomic and Metabolic Profiling of Nonulosonic Acids in Vibrionaceae reveal Biochemical Phenotypes of Allelic Divergence in V. vulnificus (accepted) Appl. Env. Microbiol.

Kline, K.A.; Schwartz, D.J.; Lewis, W.G.; Hultgren, S.J.; Lewis, A.L. Immune Activation and Suppression by Group B Streptococcus in a Murine Model of Urinary Tract Infection. (accepted) Infect.Immun.