Indian researchers have made a major discovery by understanding the role of bacteria in causing premature births (between 28 and 32 weeks of gestation) and stillbirths. At 35 per cent, India accounts for the highest burden of preterm births in the world.
The researchers found for the first time that gram positive Group B Streptococcus (GBS) bacteria were producing small balloons called membrane vesicles which contain toxins that kill both foetal and maternal cells and destroy the collagen that binds the cells together. In the lab the researchers grew the bacteria. When the culture supernatant without the bacteria was examined with electron microscopy, the researchers found numerous small spherical structures. The vesicles budding off from the bacteria were also seen, thus confirming the origin of the vesicles.
The team was led by Prof. Anirban Banerjee from the Department of Biosciences and Bioengineering, IIT Bombay and Dr. Deepak Modi from Mumbai’s National Institute for Research in Reproductive Health. The results were published on September 1 in the journal PLOS Pathogens.
Group B Streptococcus (GBS) bacteria are normally found in human vagina in 20-30 per cent of women and their numbers can shoot up in some pregnant women. The GBS bacteria have been associated with premature rupture of amniotic membrane and preterm birth. But the bacteria are rarely found in the womb so it has been difficult to prove the role of bacteria in causing preterm deliveries and stillbirths.
“Other closely related bacteria have been known to produce vesicles in very recent times. So we were interested in knowing if Group B Streptococcus bacteria were also producing vesicles,” says Prof. Banerjee, the corresponding author of the paper. “Besides curiosity, there was a scientific reason too. A lot of women who suffer from inflammation of the amniotic membrane do not have bacterial infection in the amniotic sac. So we thought that the bacteria present in the vagina were secreting certain factors that travel up the reproductive tract and acted in a synchronised fashion to cause preterm birth and stillbirth.”
The team tested its hypothesis by depositing the vesicles without the bacteria into the vagina of mice and found them throughout the reproductive tract , uterus and in the developing foetus in a matter of a few hours. They also injected the vesicles into the amniotic sac of 15 pregnant mice. All the injected mice gave birth to preterm babies and nearly 40 per cent were born dead (stillborn). The preterm babies were much smaller and unhealthy. In mice the babies were born two days preterm. “This is equivalent to two months in humans as the gestation period in mice is 21 days,” says Dr. Modi.
The researchers found the toxins present in the vesicles fragmented the collagen of the amniotic membrane. “Fragmentation of the collagen leads to loss in elasticity and weakening of the amniotic membrane thus making it susceptible to rupture due to pressure from the growing foetus,” says Dr. Modi. This leads to preterm birth. The vesicles also degrade the collagen in the womb.
The vesicles also cause inflammation in the womb. The white blood cells present at the site of inflammation produce proteins which signal the womb to undergo spontaneous and continuous contraction leading to preterm birth of babies.
“We don’t know yet how the vesicles cause stillbirth. Most probably, it must be due to toxin proteins present in the vesicles,” Dr. Modi says. The discovery opens up a huge opportunity to find drugs to prevent vesicle production by Group B Streptococcus bacteria and prevent preterm births.
The team now plans to study the placental and brain defects that might be caused by the vesicles to find how the bacteria in the vagina can damage the foetal tissues and the long term consequences of such an effect.