| dc.description.abstract | Uropathogenic Escherichia coli (UPEC) is one of the most prevalent human pathogens, causing about 80% of urinary tract infections (UTI) in the world. To establish an infection in the bladder, UPEC must survive in the gastrointestinal tract and genitourinary tract. These bodily niches present significant stresses to UPEC, including acidic pH stress. UPEC are equipped with multiple different acid resistance mechanism, however, the role these systems play during UTI has not been elucidated.In this work, I describe a new acid resistance mechanism in UPEC that utilizes serine deamination. I determine that loss of serine deamination leads to reduced survival in acidic media conditions. I show that serine is imported by UPEC under acidic media conditions. I also show that serine deamination is also important for the activation of a cross regulating two-component system, BtsS-YpdB. Through RNAseq analyses, I show that BtsS-YpdB is involved in regulating cysteine metabolism in acidic conditions, providing additional evidence of how acidic conditions impact cell metabolism. Additionally, through systematic deletion of UPEC’s acid resistance mechanism genes, I determine that lysine decarboxylation plays a key role in early bladder colonization. During bladder cell infection, the lysine decarboxylase, cadA, is upregulated in UPEC. Deletion of cadA reduces UPEC’s ability to survive within bladder cells compared to wildtype strains. Collectively, this work helps to elucidate how UPEC utilizes its acid resistance mechanisms during infection and identify lysine decarboxylation as a critical mechanism for early bladder colonization. | |
