Polysaccharide length affects mycobacterial cell shape and antibiotic susceptibility

Science Advances, vol. 6

Abstract

Bacteria control the length of their polysaccharides, which can control cell viability, physiology, virulence, and immune evasion. Polysaccharide chain length affects immunomodulation, but its impact on bacterial physiology and antibiotic susceptibility was unclear. We probed the consequences of truncating the mycobacterial galactan, an essential linear polysaccharide of about 30 residues. Galactan covalently bridges cell envelope layers, with the outermost cell wall linkage point occurring at residue 12. Reducing galactan chain length by approximately half compromises fitness, alters cell morphology, and increases the potency of hydrophobic antibiotics. Systematic variation of the galactan chain length revealed that it determines periplasm size. Thus, glycan chain length can directly affect cellular physiology and antibiotic activity, and mycobacterial glycans, not proteins, regulate periplasm size.

Authors 11

1. Alexander M. Justen

   University of Wisconsin–Madison · Massachusetts Institute of Technology

   Affiliation as printed

   Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA

   Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, USA

2. Heather L. Hodges

   University of Wisconsin–Madison

   Affiliation as printed

   Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1322, USA

3. Lili M. Kim

   University of Wisconsin–Madison

   Affiliation as printed

   Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA

4. Patric W. Sadecki

   University of Wisconsin–Madison

   Affiliation as printed

   Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1322, USA

5. Sara Porfírio

   University of Georgia

   Affiliation as printed

   Complex Carbohydrate Research Center, 315 Riverbend Rd, Athens, GA 30602, USA

6. Eveline Ultee Aachen Institute of Biology, University of Leiden

   Leiden University

   Affiliation as printed

   Institute of Biology, University of Leiden, 2333 BE Leiden, Netherlands

7. Ian M. Black

   University of Georgia

   Affiliation as printed

   Complex Carbohydrate Research Center, 315 Riverbend Rd, Athens, GA 30602, USA

8. Grace S. Chung

   University of Wisconsin–Madison

   Affiliation as printed

   Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA

9. Ariane Briegel Aachen Institute of Biology, University of Leiden

   Leiden University

   Affiliation as printed

   Institute of Biology, University of Leiden, 2333 BE Leiden, Netherlands

10. Parastoo Azadi

    University of Georgia

    Affiliation as printed

    Complex Carbohydrate Research Center, 315 Riverbend Rd, Athens, GA 30602, USA

11. Laura L. Kiessling

    Broad Institute · University of Wisconsin–Madison · Massachusetts Institute of Technology

    Affiliation as printed

    Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544, USA

    Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, USA

    Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1322, USA

    The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA