Scientists in the U.K. and B.C. have created a “lab in a cell” to study one of the world’s most-widespread, sexually transmitted diseases.
Using a gene-editing tool called CRISPR/Cas9, the researchers are able to alter the properties of white blood cells in specific ways to see how chlamydia bacteria are able to penetrate and overwhelm cells, according to microbiologist Robert Hancock of the University of B.C.
The process has already revealed new drug targets and identified key genes involved in fighting chlamydia infection, described in the journal Nature Communications.
More than 130 million people are infected each year worldwide and 100,000 cases are reported in Canada, but the real number may be much higher.
Chlamydia overwhelms a white blood cell.
Chlamydia is called “the silent disease” because in many individuals symptoms are mild to unnoticeable and that means the disease often has weeks or months to do its damage.
In men, chlamydia can lead to painful discharge and, in some cases, infertility. In women — who are least likely to have noticeable symptoms — it can lead to pelvic inflammatory disease, a painful often permanent condition.
“At that point you can take away the infection, but it doesn’t make any difference, the PID is chronic,” said Hancock, the study’s lead author.
PID is also a common cause of infertility in women.
The researchers at UBC and the Wellcome Trust Sanger Institute in the U.K. were able to overcome a significant scientific hurdle, one that can be used to unlock the secrets of other pathogens.
“The form of chlamydia that causes problems in people will only grow in people, so there are very limited options for researchers to investigate new treatments or to understand how the disease works,” he said.
Animal models are problematic. Because the human strain won’t thrive in mice they require a “mouse-adapted” strain of the bacteria, “but it’s not really the same disease.”
Instead, the researchers used human stem cells to create white blood cells called macrophages that respond to the bacteria just like cells in the body.
“With gene-editing we can knock out genes and do gene replacements and all kinds of fancy tricks, which allows you to manipulate the cell in any way you want,” he said. “Once we know how chlamydia exploits the holes in a cell’s defences, we can look for ways to toughen their armour.”
Because so-called “host-directed therapies” don’t treat the bacteria itself, chlamydia will be unable to develop resistance to these new drugs, which is an increasingly common problem for doctors treating harmful bacteria.
“You are just making the host (cell) better at preventing the infection,” he said. “It’s really cool scientifically because we can use this method not just for chlamydia, but for any human pathogen, whether it’s a virus or another bacterium.”
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