Lambda Bacteriophage and Life Cycle Regulation - Online Tutor, Practice Problems & Exam Prep

Bacteriophages, specifically Lambda Bacteriophage, exhibit two life cycles: the lytic cycle, where the virus actively replicates and lyses the host cell, and the lysogenic cycle, where it integrates into the host genome and remains dormant. The decision between these cycles is regulated by proteins such as Cro and C1, influenced by environmental conditions. In favorable conditions, Cro promotes the lytic cycle, while in poor conditions, C1 activates the lysogenic cycle. Understanding these regulatory mechanisms is crucial for insights into viral behavior and gene expression.

Bacteriophage Life Cycle

Hi. In this video, I'm going to be talking to you about Lambda Bacteriophage and its life cycle regulation. Okay. So bacteriophages, these are just viruses. "Phage" means virus. So, bacteriophage is going to be a virus that infects bacteria. Therefore, a bacteriophage is a bacterial infecting virus. We are interested in this because it provides a great example of how viruses can regulate their life cycle. We're going to focus on a particular bacteriophage, the Lambda Bacteriophage.

Bacteriophages, in general, have two life cycles, one that we call the lytic cycle. We call it that because during the cycle, the virus is actively replicating. It's producing more of itself, and it actually fills up the cell to the point where the cell can't contain it anymore, and it bursts. Another word for burst is lysis, so we call that the lytic cycle. Now, the second life cycle is the lysogenic cycle, where the virus is not actively replicating. What it does is it infects the cell and it says, "Hey, I don't really want to burst the cell; I don't really want to produce more of myself," so it just hides in the genome. It integrates itself into the genome and sits there doing nothing, just waiting until it's ready to start producing more of itself, which will eventually burst the cell. So, we call it silent; it just sits there, hiding in the genome.

To control the entrance into the lytic or the lysogenic cycle, the bacteriophage actually has two sets of genes: one that will control the lytic cycle and one that will control the lysogenic cycle. How these genes are expressed and what regulates them determines which cycle the bacteriophage enters into. We'll talk about this regulation and all those genes in much more detail in the next few videos.

So, just looking here quickly at this example, we can see that we have a virus entering into the cell, infecting it, and introducing its DNA. It has two choices: it can continue with the lytic cycle by producing more of itself, and eventually, it produces so much of itself that it has to leave the cell, and it bursts or lyses the cell for the lytic cycle. Or, it can go through the lysogenic cycle where the DNA gets integrated into the genome, and then it just sits there, replicates with the cell DNA, and does not actively produce viruses, but it integrates and replicates. This coordination of genes is one of the more complicated aspects of this entire textbook.

I want to provide you with a cheat sheet right now so that if you get confused later, you can always come back here and reorient yourself to what's going on. When the virus infects a cell, which is filled with nutrients under healthy environmental conditions, it produces more of a protein called CRO. If there are good growth conditions and there's CRO protein, then that leads to the lytic cycle. Conversely, if a virus infects a cell and the cell is deficient in nutrients, indicating poor growth conditions, then the virus will produce more lambda protein, also known as the cI protein. If there are poor growth conditions and there's more lambda or cI protein, then that leads to the lysogenic cycle. This process will become much more complicated as we follow the pathway of each of these proteins, but for now, this cheat sheet covers what you need to know: good growth conditions with CRO lead to the lytic cycle; poor growth conditions with lambda lead to the lysogenic cycle. With that, let's move on and talk more about the nitty-gritty of this process.

Bacteriophage Regulation

Okay. So now let's talk about some of the introduction to the mechanism of regulation. The lytic cycle and the lysogenic cycle genes are actually physically separated on the chromosome. Now, keep in mind, this is a circular chromosome that we're talking about. And so, I'm showing it as linear, but just keep in mind that this is actually curved. Not that it really matters, other than just, like, making sure you're aware that, you know, bacterial chromosomes are circular. So the lytic cycle, promoting the lytic cycle, has the o, p, and q genes. And the lysogenic cycle has two genes called int and cI. And so, those are two important genes, but the genes that we're mainly going to be talking about are regulatory genes. And they sit in between the lytic and lysogenic cycles, and here they are. Each one of them has different functions and is super important. We'll go through each one individually. But, this is what it looks like. So you have the lysogenic cycle genes over here, the lytic cycle genes over here, and you have all these regulatory genes here. Now, keep in mind we've been talking about operons, and remember, what does every operon have? It has a promoter, an operator, a repressor, and the genes. So although this isn't technically an operon, some of these may be operators, but the regulatory genes aren't operators. But each one of these genes, even though I'm not showing it here, has a promoter, an operator, and is a gene itself. Right? Also, all of them have terminators, as well, which I don't mention a lot but terminate transcription. So there's a lot of factors here. So if I were to write all of these, it would get very confusing. Right? Because there would be a promoter, an operator, and a terminator, a promoter, an operator, and a terminator for every single one of them. And sometimes, it actually goes in the opposite direction depending on the gene. So I'm saving you this super confusing graph of promoter, operator, terminator for each of these genes. But during the regulation, some of them get activated or repressed, and so I'm going to be writing the ones we're talking about as we're going. So let's just get started and delve in. The first two mRNAs that are transcribed are controlled through different promoters. The first gene that's transcribed is n and the second is cI. So n cI. The n has its own promoter called p_L and it has a terminator called t_L. And the cro has a promoter called pR and it's terminated by a terminator called tR1. And these genes are actually transcribed in reverse of each other. So the other thing you need to know, I'm going to show you an image, but the other thing that you need to know is that the n protein is a special type of protein called the anti-terminator protein. Now this isn't an anti-terminator structure when we talked about the tryptophan operon. This is a protein, so it's completely different. But it has the same function. So as an anti-terminator, it allows transcription to take place. What it specifically does is it allows transcription to transcribe past the terminator. So remember, the n gene and the cro both have terminators, and the N protein, when there's a lot of it, will actually bind to these terminators and block them, allowing transcription to take place. So, what this looks like—and this is how this really gets started. So you have these two mRNAs, they get transcribed first. And I don't know, my pen isn't working. Anyway, you can kind of see. Oh, I don't know why it's not working. Anyway, so the n and the cI get transcribed first. And each one of them has a promoter. Right? You can't follow my thing. Each one has a promoter and a terminator. And I've labeled them different colors, so you can see. Now they're actually transcribed in different directions. Right? Because the promoter starts transcription. So the cI is transcribed this way, and the n is transcribed the other way, which I've shown by these arrows. Now, there is n and cI protein both produced. Right? So I'm only showing n here, but if I were to write Cro all down here, there's cI protein being produced. But really what happens is a lot of n protein gets produced, and those come in and bind to both terminators. So I've shown them here as the red and the big bolded red. They're binding to the terminators. What happens is that allows for this arrow, this transcription to transcribe all the way to the end. So all the way to the lytic cycle genes and all the way to the lysogenic cycle genes. But in the meantime, what it does is it allows for the transcription of these two proteins here, c₂ and c₃. And so I'm going to talk about, and then over the next pages, what c₂ and c₃ do to regulate about which one is chosen? Because right now, both are being transcribed, and that's not what we want. What we want is to choose one over the other. And so, c₂ and c₃ are going to help us choose which cycle is going, which genes are going to be graded. But essentially, this is the first thing that happens. n and cI are transcribed, and a lot of n is made, and that binds to the terminator and that causes transcription to occur past the terminator. So with that, let's now turn the page.

Decision Between Lytic and Lysogenic Cycles

Okay. So now we're going to talk about the decision to enter into either the lysogenic or the lytic cycle. And like I said before, this is kind of the summary c1 protein, which is also called the lambda protein, which you'll notice is right here in the middle, the c1 protein, is actually what determines entrance into the lysogenic cycle. So how this happens is where we were before is that we've created a lot of n protein, and it's bound to the terminators, and that blocks termination. And so, the c2 and c3 proteins are being created or transcribed, whatever you want to do. So the important one to know about is c2. This one, here. And so the c2 protein comes in and activates another promoter called the pre promoter, and it sits here, let me disappear, so I can kind of show you this image at the same time. So the c2 protein gets created, and it binds to this promoter down here that I'm just going to draw right now, just to save you some confusion. And the P_reg is really close to this terminator. And what happens is that when the p_re is activated by the c2 protein, c1 gets created because the transcriptions happen this way. Right? So that means that you're going to get 2 types of proteins. You're gonna get anti-cro because you're transcribing cro in the opposite direction, and that's called anti-cro. And then you also get the c1 protein or the lambda protein, which is transcribed this way right here. And this protein is what's responsible for entering into the lysogenic cycle. And let me tell you why. So this is what happens. Right? So we have our n, it's transcribing, it's blocking the terminator. C2 gets produced, you get lots of it. It binds to a promoter, and it creates antichro and c1. So what happens is when you get c1, it binds to 2 operators called OR and OL, and it inhibits them. And that means that it prohibits transcription of n and cro and the longer transcripts. So, what happens is, where we were is we had, like I said, this is so confusing. Right? But you had we already talked about the n, blocking trans or blocking the terminator, allowing transcription to occur. This created c2. C2 came down here, bound the PRE promoter, created anti-cro and c1. Now, we have a lot of c1, which here in green, and we have anti-cro, and you can see c1 is all around. So what happens is c1 does a couple of things. C1 comes in, it binds to these operator regions, and what that does is it blocks transcription of this whole entire region, this whole regulatory region that we talked about. It blocks it all. So the only thing that's being produced now is antichro and c1. Then c1 also does another thing and it comes over here and it binds the p1 promoter, and this p1 promoter activates the lysogenic cycle. So this is how the lambda or the c1, whichever one you want to call it, activates entrance into the lysogenic cycle. But what happens if you actually want to, enter into the lytic cycle? So what happens is, there's actually so what happens is there ends up being more cro around. And when there's more cro around, cro can bind to 2 operators, OL and OR. And when they are inhibited, they inhibit the 2 promoters, p_L and p_R. And so what this does is it lowers the amount of cI or lambda protein in the cell. And when there's a low amount of cI in the cell, it will not inhibit anything, and it won't activate the lysogenic cycle, which I showed you up here. Right? If cI is here, it's not inhibiting this. It's not activating this. And so when ci isn't present, that means that this transcription continues, and the lytic cycle genes are extremely, are more activated than before. So what happens is if you have a lot of cro here, this will block this, the cI production. It'll block these operators, and this results in, so no cI equals transcription of the lytic cycle genes. And you might say, okay. Like, even if you follow me to this point, and you understand how, you know, these different proteins regulate their cycles. You don't understand probably at this point, why would there be more cro? Why would there be more n? Right? Because those are the 2 proteins. We said if there's more n, something happens. If there's more cro, something else happens. Well, the reason that there would be more cro is actually dependent on the conditions in the environment the bacteria is growing in. And this is because the protein called Protease. So proteases, group of proteins, they destroy, specifically, in this case, the c2 protein. And this the presence of proteases destroying this protein is what controls entrance into either the lytic or the lysogenic cycle. So, like I said before, in good growth conditions, you the bacteriophage favors the lytic cycle. And it does this because in good growth conditions, there are a lot of c2 proteases and they degrade c2. When you have less c2, the p1 promoter is not activated, and therefore, the lytic cycle is promoted. In poor growth conditions, there are few c2 proteases, meaning that there are high levels of c2. When there are high levels of c2, it activates c1 and p1, and this leads to the lysogenic cycle. So, what this looks like, let me back up. So, when there are lots of proteases. Right? So if, and lots of proteases, that's going to degrade this protein here. When this protein is degraded, that means that this one isn't created. And if this one isn't created, it can't activate this. Whereas, let me reverse and talk about this in the opposite direction. Whereas in poor growth conditions, you get a lot of this created. Right? This gets created, that means you get c1 created and because that activates c1. And when you have c1, that's going to inhibit the lytic cycle and activate the lysogenic cycle. And so that is how the growth conditions and these the levels of these proteases affect the ability of the bacteriophage to enter into the lytic and the lysogenic. So I really highly I know this is confusing, and you're probably very confused. Wish I can there was any way I can make it simpler, but I do suggest maybe going back and reviewing this and making sure you understand, you know, okay, good growth conditions that produces those proteases, that means that there won't be a lot of c2. If there's not c2, c1 won't be created, and then cone can't activate the lysogenic. Whereas if, in poor growth conditions, there's not many of them, c2 is created, that creates c1, and c1 activates lysogenic. So if you can just, like, understand that pathway and really make sure you comprehend that pathway, this this will be a breeze. But you might need to go back and review some of this a few times in order to really get it down. So, with that, let's now move on.

In which of the following life cycles does a bacteriophage integrate itself into the host genome?

• A. Lysogenic cycle
• B. Integrative cycle
• C. Lytic cycle
• D. Subdue cycle

In good growth conditions the bacteriophage is more likely to enter into which life cycle?

• A. Lysogenic cycle
• B. Integrative cycle
• C. Lytic cycle
• D. Subdued cycle

Activation of which of the following genes leads to entrance into the lysogenic cycle?

• A. N, cro, and O genes
• B. O, P, and Q genes
• C. Int and xis genes
• D. cIII genes

The N protein is an anti-terminator. What does this mean?

• A. The N protein terminates transcription
• B. The N protein allows for transcription to occur
• C. The N protein terminates translation
• D. The N protein allows for translation to occur

Which of the following proteins is mainly responsible for entering the bacteriophage into the lysogenic cycle?

• A. N protein
• B. Cro protein
• C. cI (Lambda) protein
• D. cII proteases

Here’s what students ask on this topic:

What are the main differences between the lytic and lysogenic cycles in Lambda Bacteriophage?

The lytic and lysogenic cycles are two distinct life cycles of the Lambda Bacteriophage. In the lytic cycle, the virus actively replicates within the host cell, producing numerous viral particles until the cell bursts (lyses), releasing the new viruses. This cycle is characterized by the production of Cro protein, which promotes viral replication under favorable conditions. In contrast, the lysogenic cycle involves the integration of the viral DNA into the host genome, where it remains dormant. This cycle is regulated by the C1 protein (also known as the lambda repressor), which is favored under poor growth conditions. The viral DNA replicates along with the host cell's DNA without causing immediate harm to the host.

How do environmental conditions influence the decision between the lytic and lysogenic cycles in Lambda Bacteriophage?

Environmental conditions play a crucial role in determining whether the Lambda Bacteriophage enters the lytic or lysogenic cycle. In favorable growth conditions, where nutrients are abundant, the bacteriophage produces more Cro protein, which promotes the lytic cycle. This leads to active viral replication and eventual lysis of the host cell. Conversely, in poor growth conditions, the bacteriophage produces more C1 protein (lambda repressor), which activates the lysogenic cycle. The C1 protein integrates the viral DNA into the host genome, allowing the virus to remain dormant until conditions improve. This regulatory mechanism ensures the virus can adapt to varying environmental conditions for optimal survival.

What roles do the Cro and C1 proteins play in the life cycle regulation of Lambda Bacteriophage?

The Cro and C1 proteins are key regulators in the life cycle of Lambda Bacteriophage. Cro protein is associated with the lytic cycle. Under favorable conditions, Cro promotes the transcription of genes necessary for viral replication, leading to the production of new viral particles and the eventual lysis of the host cell. On the other hand, C1 protein, also known as the lambda repressor, is crucial for the lysogenic cycle. In poor growth conditions, C1 represses the transcription of lytic genes and promotes the integration of viral DNA into the host genome, allowing the virus to remain dormant. The balance between these proteins determines the virus's life cycle.

What is the function of the N protein in Lambda Bacteriophage regulation?

The N protein in Lambda Bacteriophage acts as an anti-terminator protein, playing a crucial role in the regulation of the virus's life cycle. It allows transcription to proceed past terminators, enabling the expression of downstream genes necessary for both the lytic and lysogenic cycles. Specifically, the N protein binds to terminators and prevents them from halting transcription, thereby facilitating the production of other regulatory proteins such as C2 and C3. These proteins further influence the decision between the lytic and lysogenic cycles by activating or repressing specific promoters. Thus, the N protein is essential for the initial steps of viral gene expression and regulation.

How do the C2 and C3 proteins influence the life cycle decision in Lambda Bacteriophage?

The C2 and C3 proteins are critical in determining whether the Lambda Bacteriophage enters the lytic or lysogenic cycle. The C2 protein activates the PRE promoter, leading to the production of C1 protein (lambda repressor) and anti-Cro. High levels of C1 promote the lysogenic cycle by repressing lytic genes and integrating viral DNA into the host genome. The C3 protein stabilizes C2, protecting it from degradation by proteases. In good growth conditions, proteases degrade C2, reducing C1 levels and favoring the lytic cycle. In poor conditions, fewer proteases mean more C2 and C1, promoting the lysogenic cycle. Thus, C2 and C3 are pivotal in the life cycle decision.