Author response: Density-dependent resistance protects Legionella pneumophila from its own antimicrobial metabolite, HGA

To persist in microbial communities, the bacterial pathogen Legionella pneumophila must withstand competition from neighboring bacteria. Here, we find that L. pneumophila can antagonize the growth of other Legionella species using a secreted inhibitor: HGA (homogentisic acid). Unexpectedly, L. pneumophila can itself be inhibited by HGA secreted from neighboring, isogenic strains. Our genetic approaches further identify lpg1681 as a gene that modulates L. pneumophila susceptibility to HGA. We find that L. pneumophila sensitivity to HGA is density-dependent and cell intrinsic. Resistance is not mediated by the stringent response nor the previously described Legionella quorum-sensing pathway. Instead, L. pneumophila cells secrete HGA only when they are conditionally HGA-resistant, which allows these bacteria to produce a potentially self-toxic molecule while restricting the opportunity for self-harm. We propose that established Legionella communities may deploy molecules such as HGA as an unusual public good that can protect against invasion by low-density competitors.

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Density-dependent resistance protectsLegionella pneumophilafrom its own antimicrobial metabolite, HGA

10.1101/383018 ◽

2018 ◽

Author(s):

Tera C. Levin ◽

Brian P. Goldspiel ◽

Harmit S. Malik

Keyword(s):

Legionella Pneumophila ◽

Bacterial Pathogen ◽

Stringent Response ◽

Density Dependent ◽

Redox Active ◽

Self Harm ◽

Antimicrobial Metabolite ◽

Isogenic Strains ◽

Toxic Molecule ◽

Active Precursor

AbstractTo persist in the extracellular state, the bacterial pathogenLegionella pneumophilamust withstand competition from neighboring bacteria. Here, we find thatL. pneumophilacan antagonize the growth of neighboringLegionellaspecies using a secreted inhibitor: HGA (homogentisic acid), the unstable, redox-active precursor molecule toL. pneumophila’s brown-black pigment. Unexpectedly, we find thatL. pneumophilacan itself be inhibited by HGA secreted from neighboring, isogenic strains. Our genetic approaches further identifylpg1681as a gene that modulatesL. pneumophilasusceptibility to HGA. We find thatL. pneumophilasensitivity to HGA is density-dependent and cell intrinsic. This resistance is not mediated by the stringent response nor the previously describedLegionellaquorum-sensing pathway. Instead, we find thatL. pneumophilacells secrete HGA only when they are conditionally HGA-resistant, which allows these bacteria to produce a potentially self-toxic molecule while restricting the opportunity for self-harm. We speculate that establishedLegionellacommunities may deploy molecules such as HGA as an unusual public good that can protect against invasion by low-density competitors.

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