Density-dependent resistance protects <i>Legionella pneumophila</i> from its own antimicrobial metabolite, HGA.

Abstract

To persist in microbial communities, the bacterial pathogen <i>Legionella pneumophila</i> must withstand competition from neighboring bacteria. Here, we find that <i>L. pneumophila</i> can antagonize the growth of other <i>Legionella</i> species using a secreted inhibitor: HGA (homogentisic acid). Unexpectedly, <i>L. pneumophila</i> can itself be inhibited by HGA secreted from neighboring, isogenic strains. Our genetic approaches further identify <i>lpg1681</i> as a gene that modulates <i>L. pneumophila</i> susceptibility to HGA. We find that <i>L. pneumophila</i> sensitivity to HGA is density-dependent and cell intrinsic. Resistance is not mediated by the stringent response nor the previously described <i>Legionella</i> quorum-sensing pathway. Instead, <i>L. pneumophila</i> 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 <i>Legionella</i> communities may deploy molecules such as HGA as an unusual public good that can protect against invasion by low-density competitors.