吞下了错误的微生物，你可能会在医院的手臂上扎上一两根针——还有很多小细菌针从你体内戳来戳去。这是因为许多使我们生病的细菌使用微小的注射器状结构向我们的细胞注入蛋白质，从内部造成严重破坏。现在，研究人员已经展示了这些微生物如何将蛋白质装载到它们的纳米级针头上。
科学家们在1月3日的《自然微生物学》杂志上报告说，当单个蛋白质在活细菌体内颤抖时，他们发现微生物使用一种类似穿梭巴士的系统来装载它们的注射器:穿梭蛋白质在微生物内部随机移动，在它们前进时抓住预定注射的货物，并将其放在注射器上。了解这些细菌针头的工作原理可以帮助科学家了解如何破坏它们，或者将它们用于医学应用，比如使用细菌针头向癌细胞注射靶向药物，同时不损害健康组织。
Shuttling proteins to the syringe is “a really novel molecular mechanism that was not known before,” says microbiologist Andreas Diepold of the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany.
Under the microscope, the syringelike structures, called a type-III secretion system, look like hollow needles just wide enough for a single unfolded protein to slither through, Diepold says. A microbe’s entire surface might be covered in such needles, giving the bacterium the look of a sinister little pincushion. Scientists know the protein structure of these nanoscale needles quite well. But “we don’t know the basic question of how they recruit whatever is injected,” he says.
Previous studies suggested that a ring of proteins at the base of the secretion system, where it attaches to the bacterial cell membrane, might act something like a sorting platform that grabs target proteins and loads them into the syringe. But that work wasn’t done in living cells, says microbial geneticist Kelly Hughes of the University of Utah in Salt Lake City, who was not involved in the new study.
Other studies in live cells, including recent work by Diepold and his colleagues, hinted that the components of the sorting platform might not stay put at the bases of the syringes. Instead, they might wander around the gel-like jumble of fluids, proteins and other biological bits enclosed within a bacterium’s cell membrane, picking up and dropping off target proteins as they go — like shuttle buses.
The new study put the shuttle-bus idea to the test by using fluorescence microscopy to track the movement of individual sorting platform proteins in Yersinia enterocolitica, a stomach bug that lurks in undercooked pork. Maps of the proteins’ paths show them wandering random, zigzag paths through the cells. And experiments with mutant Y. enterocolitica that lack injectable proteins revealed that the shuttle-bus proteins move more quickly in the mutants — without any injectable targets to bind to, the shuttle-bus proteins don’t get weighed down by cargo and can diffuse faster through the cells. This showed that the sorting platform proteins don’t just wander; they also pick up passengers along the way.
“What I loved about this paper was that it was all set in vivo,” in living cells, Hughes says. “You get these beautiful pictures. And you know, a picture’s worth a thousand words.”
Unraveling more of the outstanding mysteries surrounding these microscale needles will make it easier for scientists to throw a wrench in these machines,?or to tinker with them. This type of secretion system, one of a handful of different types of needles bacteria have at their disposal, is widespread across different species of bacteria, Diepold says, so they’re good targets for new types of antibacterial drugs (SN: 3/30/22).
They’re also promising tools for medicine and biotech, Hughes says. But as much as they look like medical syringes, bacterial syringes work differently — and scientists still don’t know exactly how bacteria push proteins through their needles. It’s also unclear how the proteins that load up the needles recognize their targets. “We want to understand the riddle of how these systems work,” Diepold says. “We want to understand which solutions evolution came up with to allow bacteria to infect us.”
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