Harvard Study Shows Bacteria Overcome 1,000x Drug Dose in 11 Days

Harvard Medical School

Bacteria sensitive to antibiotics can evolve tolerance to 1,000 times a lethal dose in just 11 days through sequential genetic mutations.

AI-assisted summary of The Evolution of Bacteria on a “Mega-Plate” Petri Dish (Kishony Lab) — original source. Check the original for full context.

Source published: 2016-09-09

Key ideas

Researchers at Harvard Medical School and Technion built a 2x4 foot "Mega-Plate" Petri dish divided into nine bands to visually demonstrate large-scale bacterial evolution and drug resistance. (0:01)
The plate features a symmetrical antibiotic gradient scaling from zero on the outer edges to 1,000 times the lethal dose of standard E. coli in the center band. (0:01)
Bacteria adapted to each tenfold increase in antibiotic concentration through successive mutations, pausing at boundaries before acquiring resistance to penetrate the next zone. (0:45)
In approximately 11 days, bacteria evolved from wild-type sensitivity to surviving and thriving in 1,000 times the baseline lethal dose of antibiotic. (0:45)

Detailed notes

## Background Published on YouTube by Harvard Medical School on September 9, 2016, this video highlights an experiment conducted by scientists from the Kishony Lab at HMS and Technion. The page description explains that the team devised a large-scale, Hollywood-inspired platform to visually observe bacteria adapting, maneuvering, and developing resistance to increasingly potent doses of antibiotics.

## TL;DR To study drug resistance on a macroscopic scale, researchers built a 2x4-foot 'Mega-Plate' Petri dish featuring nine bands with antibiotic concentrations symmetrically escalating from zero at the edges to 1,000 times the lethal dose at the center. Covered in soft agar tinted with black ink, the dish allows motile white bacteria to be filmed as they spread across the surface. While the advancing bacterial front initially halts at each drug threshold, resistant mutants soon emerge and compete to colonize the formerly lethal zones. Through this successive accumulation of mutations, standard bacteria adapt to thrive in 1,000-fold antibiotic concentrations in approximately 11 days.

## Atmosphere & style The presentation is measured, scientific, and educational, driven by a clear and explanatory voiceover that methodically unpacks the experiment's construction. Visually, the stark white bacterial colonies creeping across the pitch-black agar create a mesmerizing and subtly unsettling time-lapse spectacle. The viewing experience feels both clinical and dramatic, turning an invisible microscopic evolutionary race into an accessible, visually gripping real-time invasion.

## Bulletin - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) Researchers at Harvard Medical School and Technion built a 2x4 foot "Mega-Plate" Petri dish divided into nine bands to visually demonstrate large-scale bacterial evolution and drug resistance. - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) The plate features a symmetrical antibiotic gradient scaling from zero on the outer edges to 1,000 times the lethal dose of standard E. coli in the center band. - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) Bacteria adapted to each tenfold increase in antibiotic concentration through successive mutations, pausing at boundaries before acquiring resistance to penetrate the next zone. - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) In approximately 11 days, bacteria evolved from wild-type sensitivity to surviving and thriving in 1,000 times the baseline lethal dose of antibiotic.

## Key takeaways - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) The Kishony Lab created a 2-foot by 4-foot giant Petri dish to observe bacterial movement and adaptation to drugs at a macroscopic scale. - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) The rectangular plate is segmented into nine distinct parallel bands with an escalating, symmetrical concentration of antibiotics running inward from both outer edges. - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) The outer rims contain zero antibiotic, stepping inward to a 1x threshold level barely above what standard E. coli can tolerate, then 10x, 100x, and reaching 1,000x at the central band. - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) A soft, thin top layer of agar allows the bacteria to remain motile, swimming and spreading across the gradient. - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) Black ink was incorporated into the base layer to create high contrast, allowing white bacterial growth to be tracked easily on camera. - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) Upon inoculation at the edges, wild-type bacteria rapidly populate the zero-antibiotic zones until hitting the sharp border of the drug region where they cannot survive. - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) Mutant lineages emerge near the boundary with acquired resistance, crossing the threshold and expanding into the previously lethal drug zone. - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) As resistant strains spread across an antibiotic band, they encounter and compete with other independently generated mutant lineages. - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) Advancement stalls repeatedly at each step-increase (10x, 100x, and 1,000x) until additional mutations accumulate to overcome higher concentrations. - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) Within approximately 11 days of continuous selection, bacteria evolve tolerance to thrive in 1,000 times the antibiotic dose that would have killed the ancestral strain. - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) The experiment visibly demonstrates that bacteria can accumulate successive mutations to overcome extreme concentrations of antibiotics in a very short period of time.

## Detailed walkthrough ### [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) Designing the 2x4 Foot "Mega-Plate" Petri Dish

To observe how bacteria adapt and develop resistance to drugs on a macroscopic scale, researchers constructed an oversized experimental platform modeled after standard laboratory equipment. As the narrator explains: “So what we ended up building was basically a Petri dish, except that it's 2 feet by 4 feet.” The rectangular plate is divided into nine distinct parallel bands. At the base of each band, researchers poured normal Petri-dish-thick agar infused with escalating concentrations of antibiotic, symmetrically arranged from the outer edges inward. The outermost bands contain zero antibiotic. Moving one step inward, the antibiotic level is set just barely above the threshold that standard *E. coli* can tolerate. Progressing further toward the interior, the next bands feature 10 times that concentration, followed by 100 times, until reaching the central band, which holds 1,000 times the lethal dose of antibiotic.

Over this foundational gradient, the team poured a layer of softer, thin agar that allows the bacteria motility so they can swim and spread across the surface. To make the bacterial movement visually striking and easy to film, ink was added to render the background completely black, causing the expanding colonies of bacteria to appear stark white in contrast.

```mermaid flowchart LR accTitle: Mega-Plate Antibiotic Gradient Layout accDescr: Diagram showing the symmetrical layout of antibiotic concentration bands from the outside edges to the center of the Mega-Plate.

subgraph LeftSide["Left Edge to Center"] L0["0x (No Antibiotic)"] --> L1["1x Threshold"] L1 --> L10["10x Antibiotic"] L10 --> L100["100x Antibiotic"] end

subgraph CenterBand["Plate Center"] C1000["1,000x Antibiotic"] end

subgraph RightSide["Right Edge to Center"] R0["0x (No Antibiotic)"] --> R1["1x Threshold"] R1 --> R10["10x Antibiotic"] R10 --> R100["100x Antibiotic"] end

L100 --> C1000 R100 --> C1000 ```

- **Dimensions**: 2 feet by 4 feet. - **Plate segmentation**: 9 distinct bands across the surface. - **Concentration profile**: Symmetrical gradient ranging from 0 on the outer rims, to just above survival threshold (1x), to 10x, 100x, and culminating at 1,000x in the center band. - **Visual contrast**: Black ink-tinted base layer paired with white bacterial growth for camera tracking.

---

[00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) Mutation, Competition, and Rapid Evolution Across Drug Boundaries

Once inoculated on the outer edges, the bacteria initially thrive and multiply across the zero-antibiotic region, rapidly covering the area until they hit the sharp boundary of the first antibiotic zone, where the drug concentration halts their forward progress because they can no longer survive. Soon after stopping at the perimeter, an adapted mutant emerges on the right side of the plate. Because this lineage has acquired a mutation conferring resistance to the initial drug concentration, it ventures across the line, spreading outward into the formerly lethal band until it meets and begins competing with other resistant mutants that have independently sprouted along the same front.

Upon reaching the next boundary—the 10x antibiotic zone—the front stalls once again. The bacteria pause at the threshold until new genetic variations arise that grant tolerance to the ten-fold higher dose. This sequential cycle repeats at the 100x boundary. Remarkably, after roughly 11 days of continuous growth and selection, the bacteria cross into the middle band and thrive in 1,000 times the concentration of antibiotic that would have killed the ancestral wild-type strain. Reflecting on the broader implications of the demonstration, the narrator summarizes: “And so we can see by this process of accumulating successive mutations that bacteria which are normally sensitive to an antibiotic can evolve resistance to extremely high concentrations in a short period of time.”

- **Initial colonization**: Bacteria cover the non-antibiotic territory up to the exact threshold where the drug inhibits wild-type survival. - **Mutant emergence**: Novel resistant variants break through the boundary and expand until encountering competing mutant lineages. - **Staged adaptation**: Each successive tenfold jump (1x, 10x, 100x, 1,000x) requires a distinct pause at the perimeter to accumulate compensatory and resistance mutations. - **Timeline to 1,000x resistance**: Approximately 11 days from start to complete penetration of the maximum concentration zone.

## Notable quotes > [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) And so we can see by this process of accumulating successive mutations that bacteria which are normally sensitive to an antibiotic can evolve resistance to extremely high concentrations in a short period of time.

## Mentioned Kishony Lab, Harvard Medical School, Technion, E. coli

## Video description In a creative stroke inspired by Hollywood wizardry, scientists from the Kishony Lab at HMS and Technion (www.technion.ac.il/en/) have designed a simple way to observe how bacteria move as they become impervious to drugs. The experiments are thought to provide the first large-scale glimpse of the maneuvers of bacteria as they encounter increasingly higher doses of antibiotics and adapt to survive—and thrive—in them.

Read the full story at https://hms.harvard.edu/news/bugs-film

Version that includes an audio description: https://youtu.be/_aASQd0Hwgw

Like Harvard Medical School on Facebook: https://goo.gl/4dwXyZ Follow on Twitter: https://goo.gl/GbrmQM Follow on Instagram: https://goo.gl/s1w4up Follow on LinkedIn: https://goo.gl/04vRgY

Website: https://hms.harvard.edu

[Source](https://www.youtube.com/watch?v=plVk4NVIUh8)

中文简报

哈佛研究显示细菌在11天内克服千倍药物剂量对抗生素敏感的细菌可在短短11天内通过连续的基因突变，进化出对1000倍致死剂量的耐受性。为了在宏观尺度上研究耐药性，研究人员构建了一个2x4英尺的“巨型培养皿”（Mega-Plate），其包含九个区域，抗生素浓度对称递增，从边缘的零逐渐增加到中心的1000倍致死剂量。培养皿表面覆有添加黑色墨水的软琼脂，便于对游动的白色细菌在表面蔓延的过程进行拍摄记录。虽然推进中的细菌前沿最初会在各个药物阈值处停滞，但耐药突变株很快便会涌现，并争相在原先的致死区域中定植。通过这种连续的突变累积，普通细菌在大约11天内便适应并生长于1000倍浓度的抗生素环境中。哈佛医学院与以色列理工学院的研究人员制作了一个划分为九个区域的2x4英尺“巨型培养皿”，以直观展示大规模细菌进化与耐药性。 (0:01) 该培养皿具有对称的抗生素浓度梯度，从外边缘的零递增至中心区域对标准大肠杆菌致死剂量的1000倍。 (0:01) 细菌通过连续突变适应了每次十倍增加的抗生素浓度，在穿透下一个区域之前，它们会在边界处停顿，直至获得耐药性。 (0:45) 在大约11天的时间里，细菌从野生型的敏感状态进化到能够在基线致死剂量1000倍的抗生素中生存并繁衍。 (0:45)

Reading summary

Using a two-by-four-foot 'Mega-Plate' Petri dish, researchers at Harvard Medical School demonstrated that standard bacteria can evolve resistance to 1,000 times their lethal antibiotic threshold in approximately 11 days through a stepwise process of mutation and competition. Designing the Macroscopic Antibiotic Gradient (0:01) To observe evolutionary dynamics at a visible scale, researchers constructed an experimental platform measuring 2 feet by 4 feet, divided into nine parallel bands. The foundation utilized standard-thickness agar containing a symmetrical antibiotic gradient arranged from the outer rims toward the center. The outermost bands contained no antibiotic, the adjacent interior bands were set to 1x the survival threshold for standard E. coli, and subsequent bands escalated by powers of ten to 10x, 100x, and a maximum of 1,000x the lethal concentration at the center. To allow bacterial movement across these zones, the team layered a thin, softer agar over the base so the organisms could swim and expand. The base was darkened with black ink, producing a high-contrast background that allowed white bacterial colonies to be visually tracked on camera as they progressed across the plate. Staged Adaptation and Lineage Competition (0:45) After inoculation at the plate's drug-free edges, bacteria spread quickly until hitting the boundary of the 1x zone, where the drug halted their forward progress. Expansion resumed only after a mutant acquiring drug resistance emerged and ventured across the line, eventually competing with other independently arisen mutant lineages expanding along the same front. This pattern of stalling and breakthrough repeated at each subsequent concentration jump. The bacteria paused at the 10x and 100x borders to accumulate new genetic variations conferring tolerance to the higher doses. Within roughly 11 days of continuous growth, bacterial lineages penetrated the central band and flourished in 1,000 times the antibiotic concentration that would have killed the ancestral wild-type strain. The Kishony Lab demonstration shows that normally drug-sensitive bacteria can rapidly evolve resistance to extreme antibiotic concentrations when exposed to stepped, escalating spatial gradients that allow successive mutations to accumulate.

精炼阅读摘要

哈佛医学院Kishony实验室通过构建名为“巨型培养皿”（Mega-Plate）的宏观实验平台，直观展示了细菌如何在药物边界积累突变并快速演化出极端抗药性。巨型培养皿的设计与抗生素梯度构建 (0:01) 为了在宏观尺度上清晰观察细菌适应和产生抗药性的过程，研究人员设计并制造了一个尺寸达2英尺乘4英尺（约合0.6米乘1.2米）的矩形培养皿。该培养皿被划分为9个对称的平行条带，底层灌注含有不同浓度抗生素的标准厚度琼脂。抗生素浓度从培养皿边缘向中心逐级递增：最外侧为无抗生素区（0倍），向内依次为大肠杆菌刚好无法耐受的临界浓度（1倍）、10倍、100倍，而最中央区域的抗生素浓度则高达致死剂量的1,000倍。在含有浓度梯度的底层琼脂之上，团队铺设了一层质地更软的薄琼脂层，为细菌提供游动和扩散的物理空间。为了使细菌的移动路径能够被摄像设备清晰记录，研究人员在底盘中添加了黑色墨水，与扩散过程中呈现鲜明白色的细菌菌落形成强烈的明暗对比，便于直观追踪菌群前沿的演进轨迹。突变积累与多谱系在药物边界的竞争 (0:45) 实验开始时，接种在培养皿最外缘的野生型细菌迅速繁殖并占领零抗生素区域。当菌落行进至1倍抗生素区域的边界时，由于药物阻断了野生型菌株的生存，前锋线被迫停滞。随后，右侧区域率先演化出具有耐药突变的突变株。由于获得了抵御初始浓度的遗传优势，该谱系突破了边界进入原本致命的区域，并在扩张过程中与沿同一边界独立产生的其他抗药性突变株相遇并展开生存竞争。随着种群推进到更高浓度的10倍和100倍抗生素边界，相似的停顿与突破过程重复上演。每次细菌前锋在接触更高浓度阈值时都会暂时停止扩散，直到种群内产生能够耐受十倍剂量的新遗传变异。经历大约11天的持续生长与自然选择，细菌最终攻入中心区域，在足以杀死原始野生型菌株1,000倍剂量的抗生素环境中繁衍开来。研究人员指出，该演示直接证明了细菌可以通过连续积累基因突变的方式，在约11天的较短时间内从对药物敏感的状态演化出对极高浓度抗生素的耐药性。

Detailed notes — zh

## Background 该视频由哈佛医学院（Harvard Medical School）于 2016 年 9 月 9 日发布在 YouTube 平台上。视频简介介绍，哈佛医学院及以色列理工学院的 Kishony 实验室受好莱坞视觉创意的启发，设计了一种名为“MEGA-Plate”的简易装置，首次在大尺度空间下直观展示了细菌在遭遇越来越高剂量抗生素时如何移动、适应并蓬勃生长的演化全过程。 ## TL;DR 研究人员打造了一个长 4 英尺、宽 2 英尺的巨型培养皿，将其划分为 9 个对称条带，抗生素浓度从外缘的 0 倍向中央递增至致死量的 1000 倍。实验中，原本对抗生素极其敏感的大肠杆菌在外侧无药区域迅速蔓延，并在遭遇药物屏障时停滞，直到自发突变产生耐药株冲破防线。在随后的进程中，不同突变株相互竞争，并在每一次撞击更高浓度的边界时再次停滞并积累继发突变。整场演化仅历时约 11 天，细菌便成功攻占了浓度高达最初致死阈值 1000 倍的中心区域，生动揭示了细菌在极短时间内产生超级耐药性的机制。 ## Atmosphere & style 视频整体呈现出一种严谨、沉稳且极具视觉冲击力的科学纪录片质感。黑色底色衬托下白色菌群如潮水般层层推移，配合解说员平静清晰的画外音，营造出一种既震撼又略带惊悚的观感——观众仿佛亲眼目睹生命的演化被按下快进键，在短短两分钟内目睹耐药性如何在无形中突破人类筑起的药物防线。 ## Bulletin - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) 哈佛医学院与以色列理工学院的 Kishony 实验室设计了一个长 4 英尺、宽 2 英尺的巨型培养皿（MEGA-Plate），首次大规模直观展示细菌在药物梯度压力下的空间演化。 - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) 培养皿被划分为 9 个对称条带，抗生素浓度由外向内阶梯式跃升，从零浓度一直递增至野生型大肠杆菌致死浓度的 1000 倍。 - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) 细菌在遭遇每一道浓度边界时均经历“停滞、突变、突围与相互竞争”的周期，仅历时约 11 天便成功演化出耐受千倍致死浓度的超强耐药性。 ## Key takeaways - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) 研究团队开发了尺寸达 2x4 英尺的巨型培养皿（MEGA-Plate），提供观察细菌迁移与药物适应的大尺度空间。 - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) 培养皿底部被分成 9 个平行条带，抗生素浓度呈现由两翼向正中对称递增的阶梯式分布。 - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) 浓度阶梯设计极为悬殊，从最外侧的无抗生素区，依次跃升至微量阈值、10 倍、100 倍，中央核心带高达野生型极限的 1000 倍。 - [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) 装置采用双层琼脂结构，底层含有不同抗生素浓度及黑色墨水，表层薄琼脂利于细菌自由游移，提供了极高的黑白对比可视化效果。 - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) 实验开始后，大肠杆菌首先迅速占满无抗生素区域，但在接触到无法耐受的抗生素边界时被完全阻挡。 - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) 在浓度交界处停滞一段时间后，自发产生的耐药突变株率先突破防线，并开始与周围其他突变株竞争生长空间。 - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) 面对 10 倍与 100 倍等更高浓度的边界，细菌群体重复经历“边缘停顿、积累继发突变、向前突破”的阶梯式演化进程。 - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) 仅耗时约 11 天，最初对药物高度敏感的大肠杆菌便跨越全部防线，成功侵入并繁衍于 1000 倍致死浓度的中央区域。 - [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) 实验证明，在连续的抗生素梯度选择压力下，敏感细菌能够在极短的时间内连续积累突变，演化出对超高浓度药物的耐药性。 ## Detailed walkthrough ### [00:01](https://www.youtube.com/watch?v=plVk4NVIUh8&t=1s) 巨型培养皿（MEGA-Plate）的构造与抗生素浓度梯度设计为了直观观察细菌在抗生素压力下的演变与移动过程，研究团队设计并制作了一个规格极其特殊的培养装置。这实质上是一个尺寸被放大到 2 英尺宽、4 英尺长（约 60 厘米乘 120 厘米）的巨型培养皿。整个平皿底部被划分成 9 个平行条带，每个条带底层都铺设了具有常规培养皿厚度的琼脂层，并添加了浓度梯度不同的抗生素。条带中的药物浓度呈对称且由外向内阶梯式递增分布：最外侧两侧的条带完全不含抗生素；紧挨着向内的一层，抗生素浓度略微超过普通大肠杆菌（E. coli）的生存极限；再向内一层抗生素浓度直接跃升至前一阶段的 10 倍；更向内一层为 100 倍；最核心的中央条带抗生素浓度则高达野生型致死浓度的 1000 倍。在这些厚琼脂条带之上，研究人员整体浇筑了一层薄琼脂覆盖层，以便细菌能够在表面自由游动。为了形成强烈的视觉对比，平皿底层添加了黑色墨水作为背景，使生长扩散的细菌菌群呈现为清晰醒目的白色。 - **装置尺寸**：长 4 英尺、宽 2 英尺的大型长方形培养皿。 - **条带结构与浓度梯度**：共设 9 个条带，自两翼至正中分别为：0 倍（无抗生素）、微量（略高于野生型存活阈值）、10 倍、100 倍，中央区域为 1000 倍抗生素浓度。 - **双层琼脂与视觉呈现**：底层为含有不同抗生素浓度及黑色墨水的厚琼脂，表层为便于细菌游移的薄琼脂，白色菌群在黑色底色衬托下高度可视化。 ```mermaid flowchart LR accTitle: MEGA-Plate Antibiotic Concentration Gradient accDescr: Diagram showing the symmetrical gradient of antibiotic concentrations from outer edges to center. subgraph Plate["巨型培养皿 (2x4 英尺) 浓度分布"] direction LR L0["外侧: 0x (无抗生素)"] --> L1["微过量 (阈值浓度)"] L1 --> L10["10x 浓度"] L10 --> L100["100x 浓度"] L100 --> C1000["中心带: 1000x 浓度 (致死量千倍)"] R100 <-- L1000[" "] R100["100x 浓度"] --> C1000 R10["10x 浓度"] --> R100 R1["微过量 (阈值浓度)"] --> R10 R0["外侧: 0x (无抗生素)"] --> R1 end ``` --- ### [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) 连续突变的演化进程与超高浓度耐药性的快速形成实验启动后，首先可以观察到细菌迅速在完全没有抗生素的外侧区域扩散蔓延，直至触碰并止步于它们无法耐受的抗生素边界。在边界停滞一段时间后，画面右侧率先出现了一个关键的耐药突变株。正如解说所描述的：“它具有抗生素耐药性。它不断扩散，直到开始与周围的其他突变株展开竞争。” 随着这些初代耐药菌株继续推进并撞上更高浓度的下一道边界，它们同样必须再次停下脚步，在边缘经历选择并积累新的基因突变，进而冲破屏障侵入 10 倍浓度的抗生素区域。各路突变株在 100 倍浓度边界前反复上演这一“暂停、突变、突围”的过程。历经大约 11 天的时间，细菌最终成功跨越了所有防线，侵入到抗生素浓度高达野生型极限 1000 倍的中央区域。正如研究人员最终总结指出的：“通过这种连续积累突变的过程，我们能够看到，通常对抗生素敏感的细菌可以在极短的时间内演化出对极高浓度药物的耐药性。” - **突变扩散特征**：细菌先填满零抗生素区，在边界停顿直至自发耐药突变产生，随后新突变株形成扇形前锋向前推进，并与其他突变株争夺生长空间。 - **阶梯式跃迁**：每一次跨越浓度屏障（从阈值到 10 倍、再到 100 倍），细菌群落都需要再次停滞并产生继发突变。 - **演化时间与耐药倍数**：仅耗时约 11 天，最初对药物极其敏感的大肠杆菌便演化出了能够承受 1000 倍原致死浓度的超强耐药能力。 ## Notable quotes > [00:45](https://www.youtube.com/watch?v=plVk4NVIUh8&t=45s) 通过这种连续积累突变的过程，我们能够看到，通常对抗生素敏感的细菌可以在极短的时间内演化出对极高浓度药物的耐药性。 — 研究人员 ## Mentioned 巨型培养皿 (MEGA-Plate), 大肠杆菌 (E. coli), Kishony Lab, Harvard Medical School (HMS), Technion ## Video description In a creative stroke inspired by Hollywood wizardry, scientists from the Kishony Lab at HMS and Technion (www.technion.ac.il/en/) have designed a simple way to observe how bacteria move as they become impervious to drugs. The experiments are thought to provide the first large-scale glimpse of the maneuvers of bacteria as they encounter increasingly higher doses of antibiotics and adapt to survive—and thrive—in them. Read the full story at https://hms.harvard.edu/news/bugs-film Version that includes an audio description: https://youtu.be/_aASQd0Hwgw Like Harvard Medical School on Facebook: https://goo.gl/4dwXyZ Follow on Twitter: https://goo.gl/GbrmQM Follow on Instagram: https://goo.gl/s1w4up Follow on LinkedIn: https://goo.gl/04vRgY Website: https://hms.harvard.edu [Source](https://www.youtube.com/watch?v=plVk4NVIUh8)

Source quotes

[0:45] 研究人员: 通过这种连续积累突变的过程，我们能够看到，通常对抗生素敏感的细菌可以在极短的时间内演化出对极高浓度药物的耐药性。

Source quotes

[0:45] And so we can see by this process of accumulating successive mutations that bacteria which are normally sensitive to an antibiotic can evolve resistance to extremely high concentrations in a short period of time.

Original transcript

[0:01] So what we ended up building was basically a Petri dish, except that it's 2 feet by 4 feet. [0:06] And the way we set it up is that there are nine bands, and at the base of [0:11] each of these bands we put a normal Petri-dish-thick agar with different [0:15] amounts of antibiotic. On the outside there's no antibiotic; just in from that [0:21] there's barely more than the E. coli can survive; inside of that, there's 10 [0:26] times as much; a 100 times; and then finally the middle band has a thousand [0:30] times as much antibiotic. And then across the top of it [0:34] we pour some thin agar that bacteria can move around in. The background is black [0:38] because there's ink in it, and the bacteria appear as white. [0:45] First you see they spread in the area where there's no antibiotic up until the [0:50] point that can no longer survive. Then a mutant appears on the right. [0:57] It's resistant to the antibiotic. It spreads until it starts to compete with other mutants around it. [1:05] When these mutants hit the next boundary, they too have to pause and [1:09] develop new mutations to make it into 10 times as much antibiotic. [1:18] And then you see the different mutants repeat this at 100, [1:27] and after about 11 days, they finally make it into 1000 times as much [1:33] antibiotic as the wild-type can survive. And so we can see by this process of [1:39] accumulating successive mutations that bacteria which are normally sensitive to [1:45] an antibiotic can evolve resistance to extremely high concentrations in a short period of time.