沙门氏菌的隐藏技能 | Nature Podcast

来源：Nature自然科研

又到了每周一次的 Nature Podcast 时间了！欢迎收听本周由Benjamin Thompson和 Shamini Bundell 带来的一周科学故事，本期播客片段讨论沙门氏菌在抗生素抗药性传播中的作用。欢迎前往iTunes或你喜欢的其他播客平台下载完整版，随时随地收听一周科研新鲜事。

音频文本：

Interviewer: Benjamin Thompson

First up on the show, I’ve been finding out about Salmonella bacteria lying in stasis and how they could be a hidden source of antibiotic resistance. In this case, we’re talking about Salmonella Typhimurium – a type of Salmonella that can cause nasty bouts of food poisoning. It’s a common infection, with millions of people getting it each year. Now, when this bacterium gets into someone’s gut – perhaps via an undercooked burger – it has to compete with the person’s gut bacteria for nutrients. If it’s able to gain a foothold in the centre of the intestine, the space known as the lumen, the infection can progress, as Wolf Hardt from ETH Zurich in Switzerland explains.

Interviewee: Wolf Hardt

Once it has achieved this, it starts to invade into gut tissues and this tissue invasion is causing a response of your gut’s immune system that tries to protect you, but in principle, this is causing the disease symptoms that you then experience.

Interviewer: Benjamin Thompson

The symptoms of a Salmonella food poisoning infection can be very unpleasant, but, thankfully, in most cases they only last a few days. However, Salmonella Typhimurium is a tricky beast – some of the cells in an infection have the ability to go into a sort of reversible state of suspended animation within gut tissue, becoming what are known as ‘persister’ cells. And these cells are super hardy when in this persister state. For example, they become temporarily impervious to antibiotics that would otherwise kill them. This ability makes treating an infection pretty tricky.

Interviewee: Wolf Hardt

So, you cannot use antibiotics for Salmonella diarrhoea therapy, and the reason is you will be able to clear the fast-growing Salmonella cells from the gut lumen, but as soon as you stop the antibiotic treatment, some Salmonella from somewhere – we assume from the gut tissue – will reseed your gut lumen and you are just as sick as before.

Interviewer: Benjamin Thompson

Wolf and his colleagues have been looking at Salmonella’s talent for temporary invulnerability, and they’re particularly interested in whether these cells could also be a reservoir of genetic resistance. They wanted to know whether persister cells could pass on antibiotic resistance genes to other bacteria in the gut, and they’ve got a research paper about it in this week’s Nature. Now, bacteria are extraordinarily promiscuous, and regularly share genes among themselves. One of the ways they do this is by passing tiny circles of DNA called plasmids from a donor to a recipient. That’s one of the ways that antibiotic resistance genes can spread. To find out the role that reawakened persister cells play in this promiscuity, the research team infected mice with a strain of Salmonella Typhimurium that contained a plasmid with an antibiotic resistance gene. They infected the mice either orally or by injection and then treated them with a different antibiotic – not one that the Salmonella was resistant too. This then killed off any free-living Salmonella, leaving just the persister cells hiding out in intestines of the mice.

Interviewee: Wolf Hardt

Then we were entering into a second phase of this experiment. We were asking what happens if we are now adding a second bacteria strain that doesn’t carry the plasmid yet into the mouse gut, so we could orally infect mice with a second wave of bacteria and then we could ask can we see at all that the resistance plasmids would end up in the population of the bacteria from the second wave, and the quick answer is yes, it did.

Interviewer: Benjamin Thompson

For this second wave, the team introduced both a strain of Salmonella lacking the resistance plasmid and a strain of E. coli, which is a common gut bacteria. They found that the resistance plasmid, hidden safely away in the persister cells, was able to spread to both sets of newcomers. And this happened quickly. In fact, only a small number of reawakened persisters and a couple of days were needed before 99% of the new bacteria carried the plasmid. What’s more, this transfer happened without any selective pressure. Normally, bacteria only keep hold of a plasmid giving resistance to antibiotic X, say, if antibiotic X is present. In this case though, the Salmonella persisters were never exposed to antibiotic X, and yet they kept hold of the plasmid and were able to pass it on. Wolf thinks that this system is an important one to consider when thinking about how antibiotic resistance can spread. 

Interviewee: Wolf Hardt

So far, the general feeling is that the overuse of antibiotics is the key driver of this spread, and this is certainly true because as soon as you apply an antibiotic to animals or to infected people, you will select and help the resistance plasmid-carrying bacteria to bloom up, but we would like to point out that there are other mechanisms that will also help to spread resistance plasmids, and in our case, no use of antibiotics is actually involved.

Interviewer: Benjamin Thompson

Nathalie Balaban from the Hebrew University of Jerusalem also looks at antibiotic resistance in persister cells, but wasn’t involved in this research. She was impressed with the way it was carried out.

Interviewee: Nathalie Balaban

They really did very extensive work with different systems, doing it in vivo because experiments on persisters are often done in vitro where it’s much easier. Being able both to study this in a different model and then also to directly visualise persisters from the gut tissue itself is really a tour de force.

Interviewer: Benjamin Thompson

Of course, it’s important to note that this work was done in mice, so we’ll have to wait and see whether this method of spreading antibiotic resistance is of importance in other animals or humans. But if it is, what’s to be done to prevent this pool of persistent cells spreading antibiotic genes in the environment? Wolf’s got an idea.

Interviewee: Wolf Hardt

Well, the most efficient way to solve this problem is to prevent the infection, and we found out that you can actually reduce the formation of these persister cell reservoirs in the host tissue if you vaccinate the host before you infect with these plasmid-carrying Salmonella.

Interviewer: Benjamin Thompson

Wolf suggests that a vaccination strategy could be of particular relevance in an agricultural setting, where animals can be infected by multiple strains of Salmonella. Preventing the spread of antibiotic resistance is something that’s been highlighted by governments as being of worldwide importance, but achieving this will require a greater understanding of the underlying mechanisms, as Nathalie explains.

Interviewee: Nathalie Balaban

I think that new ideas come from these basic research directions and persisters is one example of a phenomenon that was seen in labs that can explain the failure of antibiotic treatment, so it is a fascinating example of a very basic science idea that slowly gains attention in the medical world that may lead to understand how to get rid of resistant bacteria by a different mode.

Host: Benjamin Thompson

That was Natalie Balaban from the Hebrew University of Jerusalem in Israel. You also heard from Wolf Hardt from ETH Zurich in Switzerland. You can read his paper over at nature.com.ⓝ

Nature Podcast每周为您带来科学世界的全球新闻故事，覆盖众多科研领域，重点讲述Nature期刊上激动人心的研究故事。我们将话筒递给研究背后的科学家，呈现来自Nature记者和编辑的深度分析。在2017年，来自中国的收听和下载超过50万次，居全球第二。

↓↓iPhone用户长按二维码进入iTunes订阅

 ↓↓安卓用户长按二维码进入推荐平台acast订阅

点击“阅读原文”访问Nature官网收听完整版播客