The Levin lab studies the evolution of infectious diseases, seeking to understand how evolutionary “arms races” between hosts and pathogens dynamically shape the biology of immunity and pathogenesis. We approach these questions using a combination of high-throughput genetics, microbiology, and evolutionary genomics, focusing on the opportunistic pathogen Legionella pneumophila and its natural hosts, environmental amoebae.

Through this work, we are excited to discover general principles for how bacteria and hosts drive each others’ evolution.

Our questions include:

  • How do new opportunistic pathogens arise? Specifically, what sorts of host-microbe or microbe-microbe interactions select for these new pathogens to emerge?

  • How do evolutionary arms races alter the molecular weaponry of pathogens, as well as the defensive strategies of hosts?

  • How do new molecular mechanisms of immunity and pathogenesis arise?


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We use Legionella bacteria to study the evolution of new human pathogens

Legionella normally live in water and soil, where they encounter predators, such as environmental amoebae. When Legionella gets eaten by amoeba cells, they can avoid being digested by injecting effector proteins into the host cell. These effectors hijack many aspects of host cell biology, allowing the bacteria to massively replicate in the cell, explode out of the host, and continue its lifecycle.

When Legionella get inhaled by humans, they use these same effectors to infect and hijack human macrophages, causing a pneumonia-like illness called Legionnaires’ disease. Our lab seeks to understand how adaptation to amoebae has shaped Legionella’s molecular machinery, thereby facilitating the emergence of a new pathogen.


Fruiting bodies of  Dictyostelium discoideum  amoebae. Image credit: Usman Bashir

Fruiting bodies of Dictyostelium discoideum amoebae. Image credit: Usman Bashir

Dictyostelium amoebae and the ancestry of innate immunity

We use Dicty as genetically tractable hosts to study co-evolution between Legionella and environmental amoebae.

These amoebae also share many aspects of innate immunity with animal cells, and so can illuminate the origin and evolution of host defense mechanisms.


Central line of  L. pneumophila  inhibits the growth of nearby  L. micdadei

Central line of L. pneumophila inhibits the growth of nearby L. micdadei

Battles between bacteria for environmental persistence

When Legionella are outside the amoeba cell, they need to survive and compete in a world filled with other species of bacteria. We discovered that L. pneumophila uses the molecule HGA to inhibit the growth of other Legionella species.

Surprisingly, L. pneumophila can itself be inhibited by HGA when at low-density, although they are resistant at high density. We are now investigating how this paradoxical, density-dependent resistance happens.