Mycobacteriophage Lysin B is a novel mycolylarabinogalactan esterase

Authors

  • Kimberly Payne,

    1. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
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  • Qingan Sun,

    1. Department of Biochemistry and Biophysics, 103 Biochemisty/Biophysics Building, Texas A&M University, 2128 TAMU, College Station, TX 77843-2128, USA.
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  • James Sacchettini,

    1. Department of Biochemistry and Biophysics, 103 Biochemisty/Biophysics Building, Texas A&M University, 2128 TAMU, College Station, TX 77843-2128, USA.
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  • Graham F. Hatfull

    Corresponding author
    1. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
      *E-mail gfh@pitt.edu; Tel. (+1) 412 624 4350; Fax (+1) 412 624 4870.
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*E-mail gfh@pitt.edu; Tel. (+1) 412 624 4350; Fax (+1) 412 624 4870.

Summary

Mycobacteriophages encounter a unique problem among phages of Gram-positive bacteria, in that lysis must not only degrade the peptidoglycan layer but also circumvent a mycolic acid-rich outer membrane covalently attached to the arabinogalactan–peptidoglycan complex. Mycobacteriophages accomplish this by producing two lysis enzymes, Lysin A (LysA) that hydrolyses peptidoglycan, and Lysin B (LysB), a novel mycolylarabinogalactan esterase, that cleaves the mycolylarabinogalactan bond to release free mycolic acids. The D29 LysB structure shows an α/β hydrolase organization with a catalytic triad common to cutinases, but which contains an additional four-helix domain implicated in the binding of lipid substrates. Whereas LysA is essential for mycobacterial lysis, a Giles ΔlysB mutant mycobacteriophage is viable, but defective in the normal timing, progression and completion of host cell lysis. We propose that LysB facilitates lysis by compromising the integrity of the mycobacterial outer membrane linkage to the arabinogalactan–peptidoglycan layer.

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