Abstract
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.
Highlights
Inter-bacterial conflict is ubiquitous in nature, in the dense and highly competitive microenvironments of biofilms (Davey and O'toole 2000; Foster and Bell2012; Ghigo and Rendueles 2015)
We found that Legionella pneumophila (Lp) inhibited the growth of neighboring Legionella micdadei (Lm) plated 1 cm away on solid media, suggesting that it produces a secreted inhibitor (Figure 1A)
After 48h incubation, we found a 10,000-fold difference in growth between Lm antagonized by Lp versus Lm plated outside of the zone of inhibition (Figure 1B)
Summary
Inter-bacterial conflict is ubiquitous in nature, in the dense and highly competitive microenvironments of biofilms (Davey and O'toole 2000; Foster and Bell2012; Ghigo and Rendueles 2015). One strategy for managing these environments is for bacteria to cooperate with their kin cells, sharing secreted molecules as public goods (Nadell, Drescher, and Foster 2016; Abisado et al 2018). These public goods are vulnerable to exploitation by other species or by ‘cheater’ bacterial strains that benefit from public goods but do not contribute to their production. For this reason, many bacteria participate in both cooperative and antagonistic behaviors to survive in multispecies biofilms. Narrowly targeted mechanisms may seem to be of less utility than those that enable antagonism against diverse bacterial competitors, targeted strategies can be critical for bacterial success because they tend to mediate competition between closely-related organisms that are most likely to overlap in their requirements for restricted nutrients and niches (Hibbing et al 2010)
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