TY - JOUR
T1 - Combinatorial selection in amoebal hosts drives the evolution of the human pathogen Legionella pneumophila
AU - Park, Jason M.
AU - Ghosh, Soma
AU - O’Connor, Tamara J.
N1 - Funding Information:
We thank J. Vogel, M. Hossain and S. Rego for thoughtful review of the manuscript. We are grateful to R. Isberg (Tufts University School of Medicine) for sharing data, R. Isberg, J. Vogel (Washington University School of Medicine) and N. Cianciotto (Northwestern University School of Medicine) for plasmids and/or strains, and H. Shuman (University of Chicago School of Medicine) for Legionella species. This work was supported by the United States National Institutes of Health (grant no. AI119580-01) to T.J.O.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Virulence mechanisms typically evolve through the continual interaction of a pathogen with its host. In contrast, it is poorly understood how environmentally acquired pathogens are able to cause disease without prior interaction with humans. Here, we provide experimental evidence for the model that Legionella pathogenesis in humans results from the cumulative selective pressures of multiple amoebal hosts in the environment. Using transposon sequencing, we identify Legionella pneumophila genes required for growth in four diverse amoebae, defining universal virulence factors commonly required in all host cell types and amoeba-specific auxiliary genes that determine host range. By comparing genes that promote growth in amoebae and macrophages, we show that adaptation of L. pneumophila to each amoeba causes the accumulation of distinct virulence genes that collectively allow replication in macrophages and, in some cases, leads to redundancy in this host cell type. In contrast, some bacterial proteins that promote replication in amoebae restrict growth in macrophages. Thus, amoebae-imposed selection is a double-edged sword, having both positive and negative impacts on disease. Comparing the genome composition and host range of multiple Legionella species, we demonstrate that their distinct evolutionary trajectories in the environment have led to the convergent evolution of compensatory virulence mechanisms.
AB - Virulence mechanisms typically evolve through the continual interaction of a pathogen with its host. In contrast, it is poorly understood how environmentally acquired pathogens are able to cause disease without prior interaction with humans. Here, we provide experimental evidence for the model that Legionella pathogenesis in humans results from the cumulative selective pressures of multiple amoebal hosts in the environment. Using transposon sequencing, we identify Legionella pneumophila genes required for growth in four diverse amoebae, defining universal virulence factors commonly required in all host cell types and amoeba-specific auxiliary genes that determine host range. By comparing genes that promote growth in amoebae and macrophages, we show that adaptation of L. pneumophila to each amoeba causes the accumulation of distinct virulence genes that collectively allow replication in macrophages and, in some cases, leads to redundancy in this host cell type. In contrast, some bacterial proteins that promote replication in amoebae restrict growth in macrophages. Thus, amoebae-imposed selection is a double-edged sword, having both positive and negative impacts on disease. Comparing the genome composition and host range of multiple Legionella species, we demonstrate that their distinct evolutionary trajectories in the environment have led to the convergent evolution of compensatory virulence mechanisms.
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U2 - 10.1038/s41564-019-0663-7
DO - 10.1038/s41564-019-0663-7
M3 - Article
C2 - 31988381
AN - SCOPUS:85078500218
SN - 2058-5276
VL - 5
SP - 599
EP - 609
JO - Nature microbiology
JF - Nature microbiology
IS - 4
ER -