Research Digest

Lab notes: Scientists decipher how Salmonella survives in human cells

The pathogen that causes typhoid and gastroenteritis created a membrane network to throw bacteria-killing enzymes out of a cell.

Many disease-causing bacteria are insidious. They try to imitate or manipulate intracellular structures of human cells for their own growth and survival. Indian biologists are trying to decipher how these pathogens manipulate host cell proteins to survive and proliferate to make humans sick.

Among the bacterial pathogens which use human proteins for thriving are Mycobacterium tuberculosis which causes tuberculosis and Salmonella enterica typhimurium, causative agent of typhoid and gastroenteritis.

A team led by Dr Mahak Sharma at Indian Institute of Science Education and Research, Mohali has uncovered the mechanism of how Salmonella manages access to membranes and nutrients in human cells through structures (known as lysosomes) that hold a variety of proteins for its own growth and survival.

According to the study, pathogens have evolved several tactics to manipulate the activity of host proteins, all at aimed at creating their intracellular replicative niche (known as a vacuole). For example, M tuberculosis sucks iron and other nutrients from the host cells to prevent degradation of its own niche. On the other hand, Salmonella acquires both membrane and nutrients within a mature acidic vacuole. It avoids bacteria-killing enzymes by rerouting them out of the host cell as well as by forming an extensive network of membranes with its vacuole that dilutes these enzymes.

“We are trying to understand how lysosomal proteins; specifically the small GTP-binding proteins and their effectors facilitate cargo delivery to lysosomes. Previous studies have shown that Salmonella vacuole acquires several characteristics of the host cell lysosomes for nutrient access from this organelle but the mechanism at play was not known,” Sharma told India Science Wire.

Dr Amit Tuli of CSIR-IMTECH, Chandigarh, who collaborated for the study, further explained that “Salmonella-containing vacuole does not inhibit maturation of its vacuole but rather acquires several features of host lysosomes. Indeed, acidification of the vacuole is required for production of virulence factors that in turn help Salmonella to acquire both membranes and nutrients from the host endosomes and lysosomes.”

Researchers say Salmonella secretes a protein known as SifA that recruits a host chemical, HOPS complex, to SCV membranes. Recruitment of HOPS complex is key step leading to docking and fusion of SCVs with host endosomes and lysosomes. Blocking HOPS function prevents Salmonella replication inside its vacuolar niche but cutting off nutrient supply.

“Based on our findings, we envision that small molecules or peptide-based inhibitors that specifically block the interaction of Salmonella protein SifA with host factors including HOPS complex can potentially prevent Salmonella replication and infection in the human host,” added Sharma.

The research team included Aastha Sindhwani, Subhash B Arya, Harmeet Kaur, Divya Jagga, Amit Tuli, Mahak Sharma. The results of the study have been published in journal PLOS Pathogens.

This article was first published by India Science Wire.

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People who fall through the gaps in road safety campaigns

Helmet and road safety campaigns might have been neglecting a sizeable chunk of the public at risk.

City police, across the country, have been running a long-drawn campaign on helmet safety. In a recent initiative by the Bengaluru Police, a cop dressed-up as ‘Lord Ganesha’ offered helmets and roses to two-wheeler riders. Earlier this year, a 12ft high and 9ft wide helmet was installed in Kota as a memorial to the victims of road accidents. As for the social media leg of the campaign, the Mumbai Police made a pop-culture reference to drive the message of road safety through their Twitter handle.

But, just for the sake of conversation, how much safety do helmets provide anyway?

Lack of physical protections put two-wheeler riders at high risk on the road. According to a recent report by the World Health Organisation (WHO), more than 1.25 million people die each year as a result of road traffic crashes. Nearly half of those dying on the world’s roads are ‘vulnerable road users’ – pedestrians, cyclists and motorcyclists. According to the Indian transport ministry, about 28 two-wheeler riders died daily on Indian roads in 2016 for not wearing helmets.

The WHO states that wearing a motorcycle helmet correctly can reduce the risk of death by almost 40% and the risk of severe injury by over 70%. The components of a helmet are designed to reduce impact of a force collision to the head. A rigid outer shell distributes the impact over a large surface area, while the soft lining absorbs the impact.

However, getting two-wheeler riders to wear protective headgear has always been an uphill battle, one that has intensified through the years owing to the lives lost due on the road. Communication tactics are generating awareness about the consequences of riding without a helmet and changing behaviour that the law couldn’t on its own. But amidst all the tag-lines, slogans and get-ups that reach out to the rider, the safety of the one on the passenger seat is being ignored.

Pillion rider safety has always been second in priority. While several state governments are making helmets for pillion riders mandatory, the lack of awareness about its importance runs deep. In Mumbai itself, only 1% of the 20 lakh pillion riders wear helmets. There seems to be this perception that while two-wheeler riders are safer wearing a helmet, their passengers don’t necessarily need one. Statistics prove otherwise. For instance, in Hyderabad, the Cyberabad traffic police reported that 1 of every 3 two-wheeler deaths was that of a pillion rider. DGP Chander, Goa, stressed that 71% of fatalities in road accidents in 2017 were of two-wheeler rider and pillion riders of which 66% deaths were due to head injury.

Despite the alarming statistics, pillion riders, who are as vulnerable as front riders to head-injuries, have never been the focus of helmet awareness and safety drives. To fill-up that communication gap, Reliance General Insurance has engineered a campaign, titled #FaceThePace, that focusses solely on pillion rider safety. The campaign film tells a relatable story of a father taking his son for cricket practice on a motorbike. It then uses cricket to bring our attention to a simple flaw in the way we think about pillion rider safety – using a helmet to play a sport makes sense, but somehow, protecting your head while riding on a two-wheeler isn’t considered.

This road safety initiative by Reliance General Insurance has taken the lead in addressing the helmet issue as a whole — pillion or front, helmets are crucial for two-wheeler riders. The film ensures that we realise how selective our worry about head injury is by comparing the statistics of children deaths due to road accidents to fatal accidents on a cricket ground. Message delivered. Watch the video to see how the story pans out.

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This article was produced by the Scroll marketing team on behalf of Reliance General Insurance and not by the Scroll editorial team.