자료유형  

 학위논문

Control Number  

0017160437

International Standard Book Number  

9798383481936

Dewey Decimal Classification Number  

576

Main Entry-Personal Name  

Gwin, Celena M.

Publication, Distribution, etc. (Imprint  

[S.l.] : Yale University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

263 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-01, Section: B.

General Note  

Advisor: Rego, Hesper.

Dissertation Note  

Thesis (Ph.D.)--Yale University, 2024.

Summary, Etc.  

요약From dividing labor within communities to having a flexible response to environmental insults, phenotypic heterogeneity provides numerous benefits to microorganisms. Mycobacteria create this heterogeneity, in part, by their unique pattern of asymmetric growth and division, which generates a population of cells that varies in size, growth rate, and antibiotic susceptibility (1). The deletion of a single gene conserved exclusively in mycobacteria, known as lamA, abrogates a significant amount of this heterogeneity (2). We set out to characterize this protein of relatively unknown function using a combination of genetics, biochemistry, live cell time-lapse microscopy, and super-resolution microscopy.We show that LamA coordinates multiple proteins responsible for growth of new cell envelope material and division of daughter cells. LamA helps maintain the uneven distribution of cell envelope proteins including Wag31, MmpL3, MurJ, and the previously uncharacterized PgfA. Investigation of PgfA through time-lapse microscopy and lipid profiling, demonstrated that outer membrane synthesis drives elongation at the old pole, that PgfA is responsible for trafficking the outer membrane lipid TMM, and that altering TMM levels shifts the dependance to other lipid moieties for envelope integrity. Next, we describe that regulation of many key growth and division proteins is accomplished by differential localization via phosphorylation state, thereby altering the dynamics of cell wall biogenesis.We also found that LamA functionally interacts with proteins in the electron transport chain, despite these proteins being excluded from the tips of the cell. We demonstrate that deletion of lamA leads to more uniformity in the localization of respiratory complexes, membrane potential, and ATP concentration between daughter cells. Together, our data support a model in which LamA functions to spatiotemporally coordinate two essential systems: cell growth and respiration. Through this coupling, LamA represents a key factor in mycobacterial physiology, and further characterization of its role may broaden our understanding of why mycobacteria are outliers amongst other rod-shaped bacteria.

Subject Added Entry-Topical Term  

Microbiology.

Index Term-Uncontrolled  

Mycobacteria

Index Term-Uncontrolled  

Mycomembrane

Index Term-Uncontrolled  

Phenotypic heterogeneity

Added Entry-Corporate Name  

Yale University Microbiology

Host Item Entry  

Dissertations Abstracts International. 86-01B.

Electronic Location and Access  

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Control Number  

joongbu:654479