answer as if in an exam: Giving examples describe how two component regulatory systems can be used by bacteria to regulate transcription.

intro Regulation of Transcription by Bacterial Two-Component Regulatory Systems

Two-component regulatory systems (TCSs) are ubiquitous signal transduction mechanisms in bacteria that enable them to sense and respond to a wide range of environmental stimuli by altering gene expression.

A typical TCS is composed of two proteins:

a sensor kinase (SK) and a response regulator (RR).

Upon sensing a signal, the SK undergoes autophosphorylation on a conserved histidine residue using ATP.

This phosphate is then transferred to a conserved aspartate residue on the RR, activating it to regulate transcription.

These systems are highly prevalent in bacteria—Pseudomonas aeruginosa, for instance, employs over 100 different TCSs—and are relatively rare in eukaryotes, making them attractive targets for antimicrobial therapy.

intro Regulation of Transcription by Bacterial Two-Component Regulatory Systems

Two-component regulatory systems (TCSs)

are ubiquitous signal transduction mechanisms

in bacteria

that enable them to sense and respond to a wide range of environmental stimuli

by altering gene expression.

intro Regulation of Transcription by Bacterial Two-Component Regulatory Systems

A typical TCS is composed of two proteins:

a sensor kinase (SK) and a response regulator (RR).

intro Regulation of Transcription by Bacterial Two-Component Regulatory Systems

Upon sensing a signal,

the SK undergoes autophosphorylation on a conserved histidine residue using ATP.

Regulation of Transcription by Bacterial Two-Component Regulatory Systems

This phosphate is then

transferred to a conserved aspartate residue on the RR, activating it to regulate transcription.

Regulation of Transcription by Bacterial Two-Component Regulatory Systems

These systems are highly prevalent in?

bacteria

intro

Regulation of Transcription by Bacterial Two-Component Regulatory Systems

example

Pseudomonas aeruginosa,

employs over 100 different TCSs

and are relatively rare in eukaryotes, making them attractive targets for antimicrobial therapy.

main point 1

Once phosphorylated,

the RR often functions as

a DNA-binding transcription factor.

main point 1

Once phosphorylated,

the RR

It binds to

specific promoter regions of target genes,

influencing transcription initiation through several mechanisms:

• Recruitment of RNA polymerase (RNAP)

• Direct interaction with RNAP

• Differential DNA-binding affinity,

• In some cases, repression,

main point 1

Once phosphorylated,

the RR often functions as a DNA-binding transcription factor. It binds to specific promoter regions of target genes, influencing transcription initiation through several mechanisms:

• Recruitment of RNA polymerase (RNAP)

• to the promoter, increasing the likelihood of transcription initiation.

main point 1

Once phosphorylated,

the RR often functions as a DNA-binding transcription factor. It binds to specific promoter regions of target genes, influencing transcription initiation through several mechanisms:

• Direct interaction with RNAP,

• as in the case of the Bordetella pertussis BvgA regulator, which interacts with both the DNA and RNAP simultaneously.

main point 1

Once phosphorylated,

the RR often functions as a DNA-binding transcription factor. It binds to specific promoter regions of target genes, influencing transcription initiation through several mechanisms:

Differential DNA-binding affinity,

allowing genes to be regulated based on RR phosphorylation levels (e.g., early vs. late gene activation).

main point 1

Once phosphorylated,

the RR often functions as a DNA-binding transcription factor. It binds to specific promoter regions of target genes, influencing transcription initiation through several mechanisms:

In some cases, repression,

either directly or via activation of repressor genes.

examples

BvgAS System in Bordetella pertussis

PhoPQ and SsrB Systems in Salmonella enterica

Example 1: BvgAS System in Bordetella pertussis
The BvgAS system is

a global regulator of virulence genes.

Example 1: BvgAS System in Bordetella pertussis

BvgS is

a hybrid sensor kinase that initiates a phosphorelay upon activation.

Example 1: BvgAS System in Bordetella pertussis

The phosphorylated response regulator,

BvgA~P,

binds to promoters of over 100 virulence-associated genes.

Example 1: BvgAS System in Bordetella pertussis

Gene expression is tiered into

four classes based on BvgA~P levels

Example 1: BvgAS System in Bordetella pertussis

Gene expression is tiered into four classes based on BvgA~P levels:

• Class 1 (late).

• Class 2 (early)

• Class 3 (intermediate)

• Class 4

Example 1: BvgAS System in Bordetella pertussis

Gene expression is tiered into four classes based on BvgA~P levels:

• Class 1

• (late) genes require high BvgA~P concentrations.

Example 1: BvgAS System in Bordetella pertussis

Gene expression is tiered into four classes based on BvgA~P levels:

Class 2

(early) genes require low levels.

Example 1: BvgAS System in Bordetella pertussis

Gene expression is tiered into four classes based on BvgA~P levels:

class 3

(intermediate) genes are activated at low but repressed at high BvgA~P.

Example 1: BvgAS System in Bordetella pertussis

Gene expression is tiered into four classes based on BvgA~P levels:

Class 4 genes

are repressed by the BvgAS system.
This system acts more like a rheostat than a binary switch,

enabling fine-tuned regulation of virulence factors.

Example 2: PhoPQ and SsrB Systems in Salmonella enterica
This organism uses

multiple interconnected TCSs to regulate virulence in response to host environments.

Example 2: PhoPQ and SsrB Systems in Salmonella enterica

he PhoPQ system

senses low Mg²⁺ levels

activates numerous virulence genes,

including the SsrAB TCS,

which controls genes on the SPI-2 pathogenicity island

required for intracellular survival.

Example 2: PhoPQ and SsrB Systems in Salmonella enterica

Additionally, transcription of ssrA/ssrB requires

input from the EnvZ/OmpR TCS.

Example 2: PhoPQ and SsrB Systems in Salmonella enterica

Additionally, transcription of ssrA/ssrB requires input from the EnvZ/OmpR TCS.

listed

• OmpR~P

• SsrB~P

Example 2: PhoPQ and SsrB Systems in Salmonella enterica

Additionally, transcription of ssrA/ssrB requires input from the EnvZ/OmpR TCS.

OmpR~P

binds upstream of ssrA/ssrB.

Example 2: PhoPQ and SsrB Systems in Salmonella enterica

Additionally, transcription of ssrA/ssrB requires input from the EnvZ/OmpR TCS.

SsrB~P

binds downstream,

may autoregulate the system through overlapping DNA interactions.
This multi-layered regulation enables S. enterica to survive hostile conditions within macrophages and fine-tune its virulence gene expression.

Conclusion:

Bacterial TCSs are fundamental to transcriptional regulation, allowing cells to sense external cues and coordinate appropriate gene expression responses. Through mechanisms like DNA binding, RNA polymerase recruitment, and integration of multiple signals, TCSs enable bacteria to adapt, survive, and in many cases, become pathogenic.

Conclusion:
Bacterial TCSs are fundamental to

transcriptional regulation,

allowing cells to sense external cues and coordinate appropriate gene expression responses.

Conclusion:

Through mechanisms like ? TCSs enable bacteria to adapt, survive, and in many cases, become pathogenic.

DNA binding, RNA polymerase recruitment, and integration of multiple signals,

Conclusion:

TCSs enable bacteria to

adapt, survive, and in many cases, become pathogenic.

Silly Kangaroos Really Respond Pretty Greatly

• Silly → Sensor kinase (SK)

  • Detects environmental signal and autophosphorylates on a histidine residue.

• Kangaroos → Kinase Transfers

  • SK transfers phosphate to response regulator (RR) on an aspartate residue.

• Really → Response Regulator (RR)

  • Activated RR becomes a transcription factor.

• Respond → Regulation of transcription

  • Binds DNA, recruits or interacts with RNA polymerase, turns genes on or off.

• Pretty → Phosphorylation level-dependent control

  • Some genes require low RR~P, some high RR~P (e.g., BvgA classes).

• Greatly → Global regulation

  • One system can control dozens to hundreds of genes (e.g., PhoPQ, BvgAS).

What are two-component regulatory systems (TCSs)

TCSs are bacterial signal transduction mechanisms composed of a sensor kinase (SK) and a response regulator (RR) that regulate gene expression in response to environmental stimuli.

How does a sensor kinase (SK) function in a TCS

It autophosphorylates on a conserved histidine residue using ATP upon sensing a signal.

What happens after the sensor kinase is phosphorylated

The phosphate is transferred to a conserved aspartate on the response regulator (RR), activating it.

What is the role of a phosphorylated response regulator (RR~P)

It acts as a DNA-binding transcription factor to regulate gene expression.

How do RRs influence transcription

By recruiting RNA polymerase, interacting directly with RNAP, altering DNA-binding affinity, or repressing gene expression.

What is the BvgAS system

A TCS in Bordetella pertussis that regulates over 100 virulence-associated genes.

What are the four classes of genes regulated by BvgA~P

Class 1 (late, high BvgA~P), Class 2 (early, low BvgA~P), Class 3 (intermediate, activated at low and repressed at high BvgA~P), and Class 4 (repressed).

How does the BvgAS system function in terms of regulation

It acts like a rheostat, providing fine-tuned regulation rather than a binary switch.

What does the PhoPQ system in Salmonella sense

Low Mg²⁺ levels.

What is the role of the SsrAB TCS in Salmonella

It regulates genes on the SPI-2 pathogenicity island for intracellular survival.

Which TCS is involved in activating ssrA/ssrB transcription in Salmonella

The EnvZ/OmpR system.

How do OmpR~P and SsrB~P interact with the ssrA/ssrB promoter

OmpR~P binds upstream, and SsrB~P binds downstream, potentially autoregulating the system.

Why are TCSs considered important in bacterial pathogenesis

They allow bacteria to sense external cues and precisely regulate virulence gene expression.

Why are TCSs attractive antimicrobial targets

Because they are common in bacteria but rare in eukaryote