Ticks and their bacteria: a criminal syndicate

Ticks get a bad press, and this reputation is often justified. These animals are among the main vectors of pathogenic microorganisms not only for humans, but also for many other terrestrial vertebrates.

Olivier Duron, University of Montpellier

The list of diseases associated with tick bites and the pathogens they inoculate us with seems extensive and, frankly, rather unappetizing: Lyme disease, Crimean-Congo haemorrhagic fever, spotted fever, recurrent fever, tick-borne encephalitis and many others. (Find out more: Ticks, fleas: Lyme disease, a real time bomb).

Yet ticks don't only harbor pathogens, most of their microorganisms are actually quite harmless. Our work, led by CNRS in association with CIRAD, has recently established that certain bacteria are even necessary for tick survival. Without these symbiotic bacteria, ticks suffer an early cessation of development, leading to a slow decline. This symbiosis, so important for ticks, has its origins in their very particular diet.

From strict hematophagy to nutritional symbiosis

More than 900 species of tick are known today! Some species can be found in our hedgerows, some in tropical forests and others as far away as Antarctica. What they all have in common, however, is that they are hematophagous: they feed on blood, just like mosquitoes and fleas.

Unlike the latter, ticks feed exclusively on blood, right from the start of their lives. They are strict hematophagous. This ultra-specialized diet is not without consequences: while blood is a protein-rich food, it remains relatively poor in certain nutrients such as B vitamins. Eventually, the tick should suffer from nutritional deficiency and die. However, this is not the case, and it remains to be seen why.

While animals generally lack the ability to synthesize B vitamins, many bacteria are very good at it. But could they do it for ticks? Our first studies on ticks soon showed that they harbored pathogens, but much more commonly symbiotic bacteria.

These were found in almost all the ticks examined. The most intriguing fact is the location of these symbiotic bacteria in their bodies. Contrary to all expectations, these symbiotic bacteria are not part of the intestinal microbiota. Their lifestyle is far more specialized. They are obligate intracellular bacteria, unable to live in any environment other than a tick cell. The mode of transmission of these symbiotic bacteria is equally curious, enabling ticks to become infected even before they emerge from the egg.

Following a so-called transovarial mode of transmission, tick mothers pass on these symbiotic bacteria via their own ovaries to their future offspring. This process results in perfect transmission, with all tick eggs carrying symbiotic bacteria. The symbiotic association is thus stably maintained from one tick generation to the next. With no interruption to this chain of transmission, the association can be maintained for a long time. The oldest known example is over 14 million years old, still continuing today, and concerns ticks commonly found in dog ears. By way of comparison, 14 million years ago, the human line did not yet exist...

Bacteria supply B vitamins

It is these symbiotic bacteria that enable ticks to be strict hematophagists. Sequencing of their genomes has revealed the presence of genes enabling the biosynthesis - i.e. formation and production - of several types of B vitamins such as biotin, folic acid and riboflavin. These biosynthetic pathways are found intact and functional in all the tick symbiotic bacteria examined to date.

These B vitamins are vital for ticks, and anyone can find an original way to kill a tick: simply deprive it of these symbiotic bacteria. Adding a simple antibiotic like rifampicin to the blood that ticks feed on will rapidly eradicate the symbiotic bacteria and, in the medium term, lead to a deficiency in B vitamins. Ticks then stop growing, can no longer moult and show physical abnormalities. These are the symptoms of acute nutrient deficiency.

None of these symptoms appear if ticks deprived of symbiotic bacteria are artificially supplemented with B vitamins. By becoming strict hematophagists, ticks have become dependent on B vitamins and the bacteria capable of synthesizing them. Far from being trivial, this process has enabled ticks to diversify and spread throughout most terrestrial ecosystems. Without this symbiotic association, none of the ticks we know today would exist. And the same would undoubtedly be true of the diseases associated with them.

The origin of symbiosis revealed by genomes

But the story doesn't end there. Examination of the symbiotic bacteria's genome also helps us to understand how this symbiosis came about, and to trace its origins back in time. Most tick symbiotic bacteria belong to bacterial genera well known to doctors and veterinarians: these genera, Francisella or Coxiellacontain species that are particularly virulent for humans and other vertebrates.

These pathogenic bacteria are responsible for sometimes fatal infectious diseases such as tularemia and Q fever. Tick symbiotic bacteria have their origins precisely in these bacterial genera, but during evolution, while some Francisella and Coxiella lineages have evolved towards symbiosis with ticks, others have evolved towards virulence towards vertebrates, including man.

Today, these two major types of lineage - symbiotic versus pathogenic - have diverged, while retaining several points in common. The first is their ability to colonize and multiply in the cells of their hosts - ticks in one case, humans and other vertebrates in the other.

The second point is the need for them to synthesize B vitamins, although the purpose of this production differs profoundly. For symbiotic bacteria, this synthesis of B vitamins is the key to their mutualistic interactions with ticks. For pathogenic bacteria, this synthesis is absolutely necessary for their multiplication, and ultimately their virulence, towards human cells or other vertebrates. The same mechanism - the synthesis of B vitamins - has thus enabled radically different evolutions between symbiotic and pathogenic lineages.

What does this discovery tell us?

This symbiotic relationship illustrates the close interconnections that can be created within living organisms. A tick and its symbionts are so closely interwoven that they form a single biological entity, where one cannot live without the other.

This process is a powerful evolutionary driving force behind ecological innovations: by enabling the emergence of the ultra-specialized diet of strict hematophagy, symbiosis enabled the tick ancestor to occupy new ecological niches.

This ancestor then differentiated into multiple species as we know them today. On the scale of the research we carry out in our laboratories, this discovery also shows us that studying ticks solely through the prism of their pathogens is reductive. It thus invites us to explore new avenues of research to better understand how the diversity of the living world is generated and structured.

Olivier Duron, CNRS Research Fellow, University of Montpellier

The original version of this article was published on The Conversation.