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While most microorganisms are benign, or even essential for sustaining life, some are known to cause disease in organisms like humans, animals and plants. Intracellular pathogens — which live inside the cells of other creatures — are capable of establishing persistent and sometimes lifelong infections. Exactly how these bacteria evolved from their free-living ancestors to infect cells and cause disease, however, is not clearly understood, despite having happened multiple times. New evidence suggests that it occurred in a stepwise manner, involving both the loss, gain and repurposing of genes to change lifestyles.

In their study, molecular evolution expert Dr Max Emil Schön of Uppsala University and his colleagues investigated the diversity of microorganisms living in the world’s oceans.

The team discovered several new species distinctly related to Rickettsiales — an order of bacteria which replicate in host cells and include several notorious pathogens of humans, cattle and other animals.

For example, one species from this group, Rickettsia prowazekii, is the cause of Epidemic typhus among humans, while members of the genus Wolbachia are known to infect insects across the globe.

Dr Schön said: “To find distant relatives of Rickettsiales in oceanic waters was somewhat surprising.

“We wondered if these bacteria, like Rickettsiales, were obligate intracellular pathogens, or whether they were part of the free-living bacterioplankton.”

To discover the new bacteria, the team mined so-called metagenomic data — genetic material recovered directly from environmental samples.

In this way, researchers are able to study all the microorganisms that live in a given environment, rather than having to cultivate them in the laboratory.

Lead author and microbiologist Professor Thijs Ettema of Wageningen University & Research said: “The majority of microbial life on Earth currently can’t be grown in the lab.

“Using metagenomic data, we managed to reconstruct the genomes of these new oceanic bacteria.

“By analysing their genomes, we could predict that their lifestyles were very different from the previously known obligate intracellular Rickettsiales.”

The genomes of the new bacteria, the researchers noted, encoded many genes that are absent from their host-dependent and pathogenic relatives.

Paper co-author and evolutionary microbiologist Dr Joran Martijn of Canada’s Dalhousie University said: “Besides several metabolic genes typically absent from Rickettsiales, we found genes involved in motility, surface attachment and the formation of biofilms.

“The presence of such genes points at a free-living lifestyle.”

Furthermore, the team said, genes typically involved in pathogenic lifestyles — such as those involved in energy parasitism or host cell manipulation — were not identified in the new species.

However, the researchers did find genes that encode for a “type 4 secretion system”, a microscopic needle-like structure used by some bacteria to interact with host cells.

Dr Martijn added: “We speculate that this system is not necessarily used to interact with host cells like other Rickettsiales, but rather to kill competing bacteria, or to fend off predatory microbes.”

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By comparing the new species’ genomes with those of previously-known, pathogenic Rickettsiales, the team were able to start building a picture of how the order evolved to infect host cells and cause disease.

Professor Ettema said: “We suggest that the free-living ancestor of Rickettsiales repurposed its needle-like type 4 secretion system to interact with and manipulate host cells.

“Subsequently, many metabolic genes and genes affiliated with free-living lifestyle were lost as the ancestral Rickettsiales became more dependent on its host for metabolites and energy.

“This was then mirrored by the acquisition of genes involved in host manipulation and energy parasitism.”

With their initial study complete, the researchers are now looking to cultivate the newly-identified bacterial species in their lab — with the goal of learning more about how the Rickettsiales first evolved to become pathogenic.

The full findings of the study were published in the journal Nature Microbiology.

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