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

Abstract

To persist in the extracellular state, the bacterial pathogen Legionella pneumophila must withstand competition from neighboring bacteria. Here, we find that L. pneumophila can antagonize the growth of neighboring Legionella species using a secreted inhibitor: HGA (homogentisic acid), the unstable, redox-active precursor molecule to L. pneumophila's brown-black pigment. Unexpectedly, we find that 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. This resistance is not mediated by the stringent response nor the previously described Legionella quorum-sensing pathway. Instead, we find that 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 speculate that established Legionella communities may deploy molecules such as HGA as an unusual public good that can protect against invasion by low-density competitors.