insight - Cellular Biology - # Role of the Essential Cell Division Protein Aeg1 in the Assembly of the Bacterial Divisome

Identification of a Novel Essential Cell Division Protein Aeg1 in the Pathogenic Bacterium Acinetobacter baumannii

Q: What are the potential mechanisms by which Aeg1 recruits and activates FtsN to coordinate the assembly of the divisome?

Aeg1 likely plays a crucial role in the early stages of Z-ring assembly by anchoring to the division site along with ZipA, where it recruits FtsN. The interaction between Aeg1 and FtsN is essential for the activation of FtsQLB and FtsA, which are key components in the regulation of the divisome. By forming a complex with ZipA and FtsN, Aeg1 acts as a dynamic scaffold for recruiting downstream Fts proteins. Once FtsN is recruited to the divisome, it activates both FtsA and the FtsQLB complex, leading to the activation of FtsWI for septal peptidoglycan synthesis. This coordinated recruitment and activation process ensures the proper assembly and function of the divisome during bacterial cell division.

Q: How do the suppressor mutations in FtsA, FtsB, FtsL, and FtsW bypass the requirement of Aeg1, and what does this reveal about the hierarchical organization and regulation of the divisome?

The suppressor mutations in FtsA, FtsB, FtsL, and FtsW allow the bypass of the requirement of Aeg1 by A. baumannii by either directly activating downstream components or compensating for the absence of Aeg1 in the cell division process. For example, mutations like FtsAE202K in FtsA and FtsBE65A in FtsB can directly activate the proteins, enabling them to perform their functions without the need for Aeg1. Similarly, mutations in FtsL and FtsW can also compensate for the absence of Aeg1 by promoting the activation of downstream components in the divisome. These suppressor mutations reveal the hierarchical organization and regulation of the divisome, indicating that Aeg1 functions upstream of these proteins in the cell division process. The ability of these mutations to rescue the growth defect caused by Aeg1 depletion suggests that Aeg1 plays a critical role in coordinating the assembly and activation of the divisome components. The hierarchical organization of the divisome ensures that each component is recruited and activated in a specific order to facilitate proper cell division.

Q: Given the essentiality of Aeg1 for A. baumannii viability, how could this knowledge be leveraged to develop novel antimicrobial strategies targeting this pathogen?

The essentiality of Aeg1 for A. baumannii viability presents a promising target for the development of novel antimicrobial strategies. By understanding the role of Aeg1 in coordinating the assembly and activation of the divisome, researchers can explore potential inhibitors or disruptors of Aeg1 function to inhibit bacterial cell division and growth. One approach could involve the design of small molecule inhibitors that target the interaction between Aeg1 and FtsN, disrupting the recruitment and activation of downstream divisome components. Another strategy could focus on developing compounds that mimic the suppressor mutations in FtsA, FtsB, FtsL, and FtsW to bypass the requirement of Aeg1 and inhibit bacterial growth. Additionally, targeting Aeg1 could potentially lead to the development of combination therapies that disrupt multiple essential pathways in A. baumannii, reducing the likelihood of resistance development. Overall, leveraging the essentiality of Aeg1 for antimicrobial targeting could open up new avenues for the development of effective treatments against this pathogen.

Conceitos Básicos

Aeg1 is a previously unrecognized core component of the Acinetobacter baumannii divisome that interacts with multiple cell division proteins, including FtsN, to recruit and activate the septal peptidoglycan synthase FtsWI.

Resumo

The content describes the identification and characterization of Aeg1, a previously unrecognized essential cell division protein in the pathogenic bacterium Acinetobacter baumannii. Key highlights:

Using a conditional gene deletion method, the authors identified three previously annotated "hypothetical" genes, including aeg1 (A1S_3387), as essential for A. baumannii viability on rich medium.
Depletion of Aeg1 caused cell elongation, a phenotype associated with defects in cell division. Suppressor mutations that bypassed the requirement of Aeg1 mapped to the cell division gene ftsA, suggesting Aeg1 participates in the cell division process.
The authors demonstrated that Aeg1 interacts with multiple core divisome proteins, including ZipA, FtsK, FtsL, FtsB, and FtsN. Aeg1 colocalized with these divisome proteins at the division site.
Depletion of Aeg1 prevented the localization of these divisome proteins to the midcell, indicating Aeg1 is required for their proper recruitment.
Constitutively active mutants of FtsB, FtsL, and FtsW were able to bypass the need for Aeg1, suggesting Aeg1 functions upstream of these proteins to activate the septal peptidoglycan synthase FtsWI.
The authors propose a model in which Aeg1 acts as a scaffold to recruit FtsN, which in turn activates the FtsQLB complex and FtsA to induce the septal peptidoglycan synthesis by FtsWI, thereby playing a critical role in the assembly of the bacterial divisome.

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Estatísticas

Depletion of Aeg1 caused more than 96% of A. baumannii cells to become elongated with cell lengths ranging from 5 μm to over 10 μm.
Expression of the FtsAE202K mutant allowed the Δaeg1 strain to grow in the absence of Aeg1, while wild-type FtsA could not.
Aeg1 interacted strongly with ZipA and FtsN in the bacterial two-hybrid assay.
Expression of the FtsBE65A, FtsLQ70K, FtsWM254I, and FtsWS274G mutants bypassed the requirement of Aeg1 in A. baumannii.

Citações

"Aeg1 is a cell division protein that arrives at the division site to initiate cell division by recruiting FtsN, which activates FtsQLB and FtsA to induce the septal peptidoglycan synthase FtsWI."
"The discovery of the new essential cell division protein has provided a new target for the development of antibacterial agents."

Principais Insights Extraídos De

A unique cell division protein critical for the assembly of the bacterial divisome

by Chu,X., Wang... às www.biorxiv.org 04-25-2023

https://www.biorxiv.org/content/10.1101/2023.04.24.538182v7

Perguntas Mais Profundas

What are the potential mechanisms by which Aeg1 recruits and activates FtsN to coordinate the assembly of the divisome?

Aeg1 likely plays a crucial role in the early stages of Z-ring assembly by anchoring to the division site along with ZipA, where it recruits FtsN. The interaction between Aeg1 and FtsN is essential for the activation of FtsQLB and FtsA, which are key components in the regulation of the divisome. By forming a complex with ZipA and FtsN, Aeg1 acts as a dynamic scaffold for recruiting downstream Fts proteins. Once FtsN is recruited to the divisome, it activates both FtsA and the FtsQLB complex, leading to the activation of FtsWI for septal peptidoglycan synthesis. This coordinated recruitment and activation process ensures the proper assembly and function of the divisome during bacterial cell division.

How do the suppressor mutations in FtsA, FtsB, FtsL, and FtsW bypass the requirement of Aeg1, and what does this reveal about the hierarchical organization and regulation of the divisome?

The suppressor mutations in FtsA, FtsB, FtsL, and FtsW allow the bypass of the requirement of Aeg1 by A. baumannii by either directly activating downstream components or compensating for the absence of Aeg1 in the cell division process. For example, mutations like FtsAE202K in FtsA and FtsBE65A in FtsB can directly activate the proteins, enabling them to perform their functions without the need for Aeg1. Similarly, mutations in FtsL and FtsW can also compensate for the absence of Aeg1 by promoting the activation of downstream components in the divisome.
These suppressor mutations reveal the hierarchical organization and regulation of the divisome, indicating that Aeg1 functions upstream of these proteins in the cell division process. The ability of these mutations to rescue the growth defect caused by Aeg1 depletion suggests that Aeg1 plays a critical role in coordinating the assembly and activation of the divisome components. The hierarchical organization of the divisome ensures that each component is recruited and activated in a specific order to facilitate proper cell division.

Given the essentiality of Aeg1 for A. baumannii viability, how could this knowledge be leveraged to develop novel antimicrobial strategies targeting this pathogen?

The essentiality of Aeg1 for A. baumannii viability presents a promising target for the development of novel antimicrobial strategies. By understanding the role of Aeg1 in coordinating the assembly and activation of the divisome, researchers can explore potential inhibitors or disruptors of Aeg1 function to inhibit bacterial cell division and growth.
One approach could involve the design of small molecule inhibitors that target the interaction between Aeg1 and FtsN, disrupting the recruitment and activation of downstream divisome components. Another strategy could focus on developing compounds that mimic the suppressor mutations in FtsA, FtsB, FtsL, and FtsW to bypass the requirement of Aeg1 and inhibit bacterial growth.
Additionally, targeting Aeg1 could potentially lead to the development of combination therapies that disrupt multiple essential pathways in A. baumannii, reducing the likelihood of resistance development. Overall, leveraging the essentiality of Aeg1 for antimicrobial targeting could open up new avenues for the development of effective treatments against this pathogen.