title: Compound-gene interaction mapping reveals distinct roles for Staphylococcus aureus teichoic acids.
abstract: Staphylococcus aureus contains two distinct teichoic acid (TA) polymers, lipoteichoic acid (LTA) and wall teichoic acid (WTA), which are proposed to play redundant roles in regulating cell division. To gain insight into the underlying biology of S. aureus TAs, we used a small molecule inhibitor to screen a highly saturated transposon library for cellular factors that become essential when WTA is depleted. We constructed an interaction network connecting WTAs with genes involved in LTA synthesis, peptidoglycan synthesis, surface protein display, and D-alanine cell envelope modifications. Although LTAs and WTAs are synthetically lethal, we report that they do not have the same synthetic interactions with other cell envelope genes. For example, D-alanylation, a tailoring modification of both WTAs and LTAs, becomes essential when the former, but not the latter, are removed. Therefore, D-alanine-tailored LTAs are required for survival when WTAs are absent. Examination of terminal phenotoypes led to the unexpected discovery that cells lacking both LTAs and WTAs lose their ability to form Z rings and can no longer divide. We have concluded that the presence of either LTAs or WTAs on the cell surface is required for initiation of S. aureus cell division, but these polymers act as part of distinct cellular networks.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02139;
authors.forename: John P
authors.initials: JP
authors.lastname: Santa Maria
authors.affiliation: Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114; and.
authors.forename: Ama
authors.initials: A
authors.lastname: Sadaka
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02139;
authors.forename: Samir H
authors.initials: SH
authors.lastname: Moussa
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02139;
authors.forename: Stephanie
authors.initials: S
authors.lastname: Brown
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02139; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115.
authors.forename: Yanjia J
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02139; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Rubin
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02139; Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA 02114; and suzanne_walker@hms.harvard.edu michael_gilmore@meei.harvard.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gilmore
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02139; suzanne_walker@hms.harvard.edu michael_gilmore@meei.harvard.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
mesh_terms: D000409:Alanine / Q000378:metabolism; D002455:Cell Division; D002473:Cell Wall / Q000378:metabolism; D002874:Chromosome Mapping; D004251:DNA Transposable Elements / Q000235:genetics; D055786:Gene Knockout Techniques; D053263:Gene Regulatory Networks; D005798:Genes, Bacterial; D008070:Lipopolysaccharides / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism*; D013682:Teichoic Acids / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid; D000409:Alanine
keywords: Tn-seq; TraDIS; synthetic lethality
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