Polysaccharide length affects mycobacterial cell shape and antibiotic susceptibility.

Alexander M Justen,Ariane Briegel,Lili M Kim,Laura L Kiessling,Eveline Ultee,Grace S Chung,Ian Black,Heather L Hodges,Sara Porfirio,Parastoo Azadi,Patric W Sadecki

doi:10.1126/sciadv.aba4015

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.

Highlights

Bacteria generate cell surface polysaccharides of controlled size
Our ability to isolate a mycobacterial strain with a truncated galactan indicates that there is flexibility in chain length required for transport
M. smeg strains with truncated arabinan increase the length of their galactan, perhaps as a compensatory mechanism [7]

Summary

Introduction

Bacteria generate cell surface polysaccharides of controlled size. Biosynthesis of these glycans occurs through processes that regulate chain length [1], indicating that polysaccharide length is linked to function. The one known function for saccharide chain length is to influence the potency of immunomodulatory glycans. In Salmonella enterica, O-antigens of >100 repeat units serve as physical barriers that facilitate bacterial evasion of complement- mediated killing [2]. In mycobacteria, the cell surface glycoconjugate lipoarabinomannan (LAM) affects host immunomodulation [3]. When arabinan branching is disrupted, the mannan core of LAM is more efficiently recognized by macrophages as foreign; the host mounts a proinflammatory response [4]. The effects of polysaccharide chain length on bacterial physiology and survival are not apparent

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Results

Conclusion