Physiological and regulatory mechanisms of methylglyoxal resistance in <em>enterobacteriaceae</em> Sara Ann Alexander

Format:

Book

Thesis/Dissertation

Author/Creator:

Alexander, Sara Ann, author.

Contributor:

University of Pennsylvania. Biology., degree granting institution.

Language:

English

Subjects (All):

Microbiology.

Physiology.

Cellular biology.

Molecular biology.

0410.

0379.

0307.

0719.

Local Subjects:

Microbiology.

Physiology.

Cellular biology.

Molecular biology.

0410.

0379.

0307.

0719.

Genre:

Academic theses

Physical Description:

1 online resource (141 pages)

Contained In:

Dissertations Abstracts International 87-12B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2026

Language Note:

English

Summary:

Methylglyoxal (MGO) is a toxic electrophile produced during cellular metabolism and by immune cells during infection. To cope with MGO stress, Escherichia coli employs the glyoxalase detoxification system and Kef-mediated potassium/proton antiport, yet the Kef system is insufficient for protection under potassium concentrations relevant to infection and colonization. In this work, we identify a regulatory phosphotransferase system as a mediator of MGO resistance through modulation of intracellular potassium and pH. Higher levels of PtsN phosphorylation results in increased YcgO antiport activity, which in turn confers resistance to MGO in potassium concentrations found in mammalian hosts. We further characterize this intracellular physiological state of low potassium/pH as an SOS response-independent protective mechanism specific to MGO stress that may reduce initial DNA damage. Additionally, we identify global changes in protein abundance and specific targets of glycation in response to MGO stress in E. coli using LC-MS/MS. We then expand our investigation into other Enterobacteriaceae and determine that clinical isolates of both E. coli and Klebsiella pneumoniae are highly resistant to MGO. In K. pneumoniae, we find that this increased MGO resistance also applies to other DNA damaging agents and does not depend on the multiple copies of the error-prone DNA polymerase genes umuDC that are present in most isolates. Finally, we show that despite surviving UV radiation significantly better than E. coli, K. pneumoniae sustains an equal amount of UV-mediated DNA damage. Together our results expand current models of bacterial survival during MGO stress and reveal a previously uncharacterized capacity for genotoxic stress tolerance in K. pneumoniae

Notes:

Source: Dissertations Abstracts International, Volume: 87-12, Section: B.

Advisors: Goulian, Mark Committee members: Shin, Sunny; Pohlschröder, Mechthild; Zackular, Joseph; Zhu, Jun

Ph.D. University of Pennsylvania 2026

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798247982791

Access Restriction:

Restricted for use by site license