Bacteriophages target membrane-anchored glycopolymers to promote host cell lysis and progeny release
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Most bacteriophages lyse their host cell to release progeny virions. Double-stranded DNA phages typically promote host lysis using a holin-endolysin system. Holins form pores in the cytoplasmic membrane allowing endolysins access to the peptidoglycan (PG) cell wall, which they degrade to weaken the cell envelope and promote osmotic lysis. Phages that infect Proteobacteria also encode a spanin in their lysis cassette that functions to disrupt the host outer membrane. The spanin-requirement for cell lysis provided the first clue that the proteobacterial outer membrane confers mechanical rigidity to the cell envelope. Corynebacteria and mycobacteria also build an outer membrane, but it is made of mycolic acids instead of lipopolysaccharides. Here, we investigated whether the mycomembrane presents a mechanical barrier to phage-induced lysis of corynebacteria. In addition to annotated holin and endolysin genes, mycobacteriophages and corynephages were found to encode a membrane protein we call LysZ in their lysis cassettes. Deletion of lysZ in the corynephage Cog blocked lysis of its host Corynebacterium glutamicum . Surprisingly, disruption of the host mycomembrane did not correct this phenotype. Instead, a genetic analysis revealed that blocking synthesis of membrane-anchored glycopolymers called lipomannans/lipoarabinomannans (LM/LAMs) can restore plaque formation when LysZ is inactivated. This genetic system also identified the likely flippase that transports decaprenyl-linked mannose units to the extracellular side of the membrane for polymerization into LM/LAM. Overall, our results indicate that lipoglycans like LM/LAMs play roles in mechanically stabilizing bacterial envelopes and that phages use LysZ-like factors to overcome this barrier to promote lysis.
SIGNIFICANCE
Bacteriophages must break down the cell envelope of their host to induce cell lysis for progeny release. Mycobacteria and related corynebacteria build complex cell envelopes that are likely to be especially challenging for phages to disrupt. Here, we identify a novel lysis gene called lysZ encoded by many mycobacteriophages and corynephages. Using the model organism Corynebacterium glutamicum ( Cglu ) and its phage Cog, we show that LysZ is required to induce host lysis and that this requirement can be overcome by inactivating genes needed for the synthesis of lipid-anchored glycans called lipomannans/lipoarabinomannans (LM/LAMs). These findings reveal that LM/LAMs are likely to play a mechanical role in stabilizing the cell envelope of Cglu and its corynebacterial and mycobacterial relatives.
