Wolfe Lab - Research Overview

Protein acetylation in bacteria and its impact on transcription and other cellular processes

My laboratory is composed of two groups. One group investigates protein acetylation and its influence on bacterial physiology with an emphasis on transcription. The other group studies the female bladder microbiome and its impact on women’s health and disease. Both groups interact often.

Protein acetylation in bacteria and its impact on transcription
The global nature of reversibly lysine acetylation of proteins in bacteria is newly discovered. The regulation and impact - both global and local - of this posttranslational modification is not understood. Homologs of the enzymes that catalyze protein acetylation are widely conserved and distributed in bacteria, but with few exceptions their functions and targets remain unknown. Members of my laboratory have begun to fill in the gaps. For example, we have identified several growth conditions that dramatically alter the protein acetylation profile, suggesting that bacterial acetylation is regulated. This regulation appears to be quite sophisticated. For example, we have learned that RNA polymerase (RNAP), the complex biological machine that transcribes DNA into messenger RNA, can be acetylated on dozens of lysines on the surfaces of several RNAP subunits. Furthermore, subtle changes in environmental or genetic conditions can alter the pattern of acetylation with consequences on output. We propose that acetylation of RNAP and some of its transcription factors can exert a global impact on transcription and, thus, on diverse aspects of bacterial physiology.

The female urinary microbiome and its role in health and disease
The number of women with at least 1 pelvic floor disorder (e.g. urinary incontinence (UI) or pelvic organ prolapse (POP) is predicted to increase from 28.1 million in 2010 to 43.8 million in 2050. During this period, the number of women with UI will increase 55% from 18.3 million to 28.4 million and the number of women with POP will increase 46% from 3.3 to 4.9 million. Unfortunately for these women, the causes of UI, POP and other lower pelvic disorders remain unknown. The Group on Urinary Microbiome and its collaborators propose a novel hypothesis - the normal urinary tract is colonized by bacteria and that perturbations in the normal pattern of colonization either cause or influence the progression of certain lower pelvic disorders. This hypothesis is novel, primarily because the urinary tract has long been considered sterile. While urine cultures have been the gold standard for assessment of bacteria in the urinary tract, evidence exists that urine may not be sterile & that certain clinical conditions of the lower urinary tract may result from an imbalance in the composition of the bacteria that normally colonize the lower urinary tract. We are using 16S rRNA Next Generation Pyrosequencing to survey urine samples taken from POP/UI patients and controls. Our preliminary results suggest (1) that the urine of POP/UI patients is generally not sterile; (2) that these bacterial communities are diverse; and (3) that the composition often differs between patients. These results also suggest the possibility that the female urinary tract can become colonized by normal and abnormal vaginal flora.