Alan J. Wolfe, PhD

Alan J. Wolfe, PhD

Professor

Microbiologist

Major Research Interests: Bacterial protein acetylation and the urinary microbiome

 

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

The female urinary microbiome and its role in health and disease A broad range of lower urinary tract (LUT) diagnoses affect women; these include urinary tract infections (UTI), bladder pain syndromes, urinary incontinence (UI) and overactive bladder (OAB). LUT problems are common and costly. At least 50% of women experience a UTI during their lifetime and a critical subgroup of UTI patients experiences recurrent UTIs. Bladder pain syndromes are poorly understood and thus poorly treated, despite significant research investment. UI and OAB are also highly prevalent with substantial economic costs, accounting for >$20 billion/year in the US, and affecting 30-60% of middle-aged and older women in the general population.

The Wolfe lab is an integral part of the Loyola Urinary Education and Research Collaborative [LUEREC], a multidisciplinary translational research team co-directed by Dr. Wolfe. In 2012, LUEREC reported the first definitive evidence that bacteria colonize the normal female urinary tract, an observation subsequently confirmed by others. These results overturn the longstanding dogma that urine is sterile. This recent documentation that the FUM exists provides an opportunity to advance our understanding of the etiology of diverse LUT disorders.

Indeed, we recently reported that the bacteria that comprise the FUM are distinct from those that cause overt clinical UTI, that the FUM of women with UI differs from that of women with no LUT symptoms, and that the FUM has clinical relevance, linking it to clinical symptoms and outcomes, including associations with urinary symptom levels, treatment response, and UTI risk.

Protein acetylation in bacteria
Nε-lysine (protein) acetylation in bacteria has recently emerged as an abundant and stoichiometrically relevant post-translational modification in diverse bacteria, including both Gram-negatives and Gram-positives. There are two known mechanisms by which protein acetylation occurs. The first is the canonical enzymatic reaction catalyzed by an acetyltransferase that uses acetyl-CoA as an acetyl donor. The second mechanism is non-enzymatic acetylation that uses the small, high-energy central metabolite acetyl phosphate (acP) as the acetyl donor. As such, bacterial protein acetylation resembles eukaryotic protein acetylation, including non-enzymatic acetylation, which occurs in mitochondria. We infer that acetylation in bacteria works much like it does in eukaryotes and that it exerts a similar impact on protein function and cellular physiology.

In this context, we submit that the most important outstanding questions in this new field are the following: (i) how do bacteria regulate acetylation, (ii) does acetylation affect bacterial protein function, (iii) how does altered function affect cellular physiology and (iv) can we develop approaches to facilitate future studies? To answer these questions, we have formed a multidisciplinary collaboration with chemists, structural biologists, and chemical engineers.

Primary Peer Reviewed Research, Reviews, Book Chapters, Commentaries, and Editorials
 

1.     Bresler L, Price TK, Hilt EE, Joyce C, Fitzgerald CM, Wolfe AJ. 2019. Female lower urinary tract microbiota do not associate with IC/PBS symptoms: a case-controlled study. Int Urogynecol J. 2019 Apr 16.  doi: 10.1007/s00192-019-03942-9. [Epub ahead of print] PMID: 30993388

2.     Christensen DG, Baumgartner JT, Xie X, Jew KM, Basisty N, Schilling B, Kuhn ML, Wolfe AJ. 2019. Mechanisms, Detection, and Relevance of Protein Acetylation in Prokaryotes. MBio. 2019 Apr 9;10(2). pii: e02708-18. doi: 10.1128/mBio.02708-18. Review. PMID: 30967470

3.     Christensen DG, Meyer JG, Baumgartner JT, D'Souza AK, Nelson WC, Payne SH, Kuhn ML, Schilling B, Wolfe AJ. 2019. Identification of Novel Protein Lysine Acetyltransferases in Escherichia coli. MBio. 2019 Apr 9;10(2). pii: e00592-19. doi: 10.1128/mBio.00592-19. PMID:30967468

4.     Shannon MB, Limeira R, Johansen D, Gao X, Lin H, Dong Q, Wolfe AJ, Mueller ER. 2019. Bladder urinary oxygen tension is correlated with urinary microbiota composition. Int Urogynecol J. 2019 Mar 27. Doi: 10.1007/s00192-019-03931-y. [Epub ahead of print] PMID: 30918980

5.     Southworth E, Hochstedler B, Price TK, Joyce C, Wolfe AJ, Mueller ER. 2019.A Cross-sectional Pilot Cohort Study Comparing Standard Urine Collection to the Peezy Midstream Device for Research Studies Involving Women. Female Pelvic Med Reconstr Surg. 2019 Mar/Apr;25(2):e28e33doi:10.1097/SPV.0000000000000693.PMID:30807432

6.     Schilling B, Basisty N, Christensen DG, Sorensen D, Orr JS, Wolfe AJ, Rao CV. Global Lysine Acetylation in Escherichia coli Results from Growth Conditions That Favor Acetate Fermentation. J Bacteriol. 2019 Apr 9;201(9). pii: e00768-18. doi: 10.1128/JB.00768-18. Print 2019 May 1. PMID:30782634

7.     Bajic P, Wolfe AJ, Gupta GN. 2019. Old instillations and new implications for bladder cancer: the urinary microbiome and intravesical BCG. BJU Int. 2019 Jan 21. doi: 10.1111/bju.14683. [Epub ahead of print] PMID: 30663202

8.     Bajic P, Wolfe AJ, Gupta GN. The Urinary Microbiome: Implications in Bladder Cancer Pathogenesis and Therapeutics. Urology. 2019 Jan 4. pii: S0090-4295(19)30006-8. doi: 10.1016/j.urology.2018.12.034. [Epub ahead of print] PMID:30615894

9.     Hu LI, Filippova EV, Dang J, Pshenychnyi S, Ruan J, Kiryukhina O, Anderson WF, Kuhn ML, Wolfe AJ. 2018. The spermidine acetyltransferase SpeG regulates transcription of the small RNA rprA. PLoS One. 2018 Dec 18;13(12):e0207563. doi: 10.1371/journal.pone.0207563. eCollection 2018. PMID: 30562360

10.  Moody KJ, Tinklepaugh J, Obert E, Grohn K, DeRosa JR, Lumen E, Moyer BS, Campbell S, Wolfe AJ, Sleeper MB, Bianchi AH, Fisher C, Applegate J, Leary E, LeClair N, Wortel D, Doyle RP, Rohrer B, Blanden AR. 2018. Recombinant Manganese Peroxidase Reduces A2E Burden in Age-Related and Stargardt's Macular Degeneration Models. Rejuvenation Res. 2018 Dec;21(6):560-571. doi: 10.1089/rej.2018.2146. PMID: 30516450

11.  Wolfe AJ, Brubaker L. Urobiome updates: advances in urinary microbiome research. Nat Rev Urol. 2018 Dec 3. doi: 10.1038/s41585-018-0127-5. [Epub ahead of print] PMID:30510275

12.  Christensen DG, Meyer JG, Baumgartner JT, D'Souza AK, Nelson WC, Payne SH, Kuhn ML, Schilling B, Wolfe AJ. 2018. Identification of Novel Protein Lysine Acetyltransferases in Escherichia coli. MBio. 2018 Oct 23;9(5). pii: e01905-18. doi: 10.1128/mBio.01905-18. Erratum in: MBio. 2019 Apr 9;10(2):.PMID: 30352934

13.  Orr JS, Christensen DG, Wolfe AJ, Rao CV. Extracellular Acidic pH Inhibits Acetate Consumption by Decreasing Gene Transcription of the Tricarboxylic Acid Cycle and the Glyoxylate Shunt. J Bacteriol. 2018 Dec 20;201(2). pii: e00410-18. doi: 10.1128/JB.00410-18. Print 2019 Jan 15. PMID: 30348831

14.   Abelson B, Sun D, Que L, Nebel RA, Baker D, Popiel P, Amundsen CL, Chai T, Close C, DiSanto M, Fraser MO, Kielb SJ, Kuchel G, Mueller ER, Palmer MH, Parker-Autry C, Wolfe AJ, Damaser MS. 2018. Sex differences in lower urinary tract biology and physiology. Biol Sex Differ. 2018 Oct 22;9(1):45. doi: 10.1186/s13293-018-0204-8. Review. PMID:30343668

15.   Thomas-White KJ, Gao X, Lin H, Fok CS, Ghanayem K, Mueller ER, Dong Q, Brubaker L, Wolfe AJ. 2018. Urinary microbes and postoperative urinary tract infection risk in urogynecologic surgical patients. Int Urogynecol J. 2018 Dec;29(12):1797-1805. doi: 10.1007/s00192-018-3767-3. Epub 2018 Sep 28.PMID:30267143

16.  Wolfe AJ, Gugel JF, Chen M, Movileanu L. Kinetics of Membrane Protein-Detergent Interactions Depend on Protein Electrostatics. J Phys Chem B. 2018 Oct 18;122(41):9471-9481. doi: 10.1021/acs.jpcb.8b07889. Epub 2018 Oct 5. PMID:30251852

17.  Male Bladder Microbiome Relates to Lower Urinary Tract Symptoms. 2018. Bajic P, Van Kuiken ME, Burge BK, Kirshenbaum EJ, Joyce CJ, Wolfe AJ, Branch JD, Bresler L, Farooq AV. Eur Urol Focus. 2018 Aug 21. pii: S2405-4569(18)30220-7. doi: 10.1016/j.euf.2018.08.001. [Epub ahead of print] PMID:30143471

18.  Fok CS, Gao X, Lin H, Thomas-White KJ, Mueller ER, Wolfe AJ, Dong Q, Brubaker L. 2018. Urinary symptoms are associated with certain urinary microbes in urogynecologic surgical patients. Int Urogynecol J. 2018 Dec;29(12):1765-1771. doi: 10.1007/s00192-018-3732-1. Epub 2018 Aug 16. PMID:30116843

19.  Garretto A, Thomas-White K, Wolfe AJ, Putonti C. 2018. Detecting viral genomes in the female urinary microbiome. J Gen Virol. 2018 Aug;99(8):1141-1146. doi: 10.1099/jgv.0.001097. Epub 2018 Jun 11. PMID:29889019

20.  DeRosa JR, Moyer BS, Lumen E, Wolfe AJ, Sleeper MB, Bianchi AH, Crawford A, McGuigan C, Wortel D, Fisher C, Moody KJ, Blanden AR. 2018. RPtag as an Orally Bioavailable, Hyperstable Epitope Tag and Generalizable Protein Binding Scaffold. Biochemistry. 2018 May 29;57(21):3036-3049. doi: 10.1021/acs.biochem.8b00170. Epub 2018 May 15.

21.  Thomas-White K, Forster SC, Kumar N, Van Kuiken M, Putonti C, Stares MD, Hilt EE, Price TK, Wolfe AJ, Lawley TD. 2018. Culturing of female bladder bacteria reveals an interconnected urogenital microbiota. Nat Commun. 2018 Apr 19;9(1):1557. doi: 10.1038/s41467-018-03968-5. PMID:29674608

22.   Kramer H, Kuffel G, Thomas-White K, Wolfe AJ, Vellanki K, Leehey DJ, Bansal VK, Brubaker L, Flanigan R, Koval J, Wadhwa A, Zilliox MJ. 2018. Diversity of the midstream urine microbiome in adults with chronic kidney disease. Int Urol Nephrol. 2018 Jun;50(6):1123-1130. doi: 10.1007/s11255-018-1860-7. Epub 2018 Apr 12. PMID:29651696

23.  Wolfe AJ, Gugel JF, Chen M, Movileanu L. 2018. Detergent Desorption of Membrane Proteins Exhibits Two Kinetic Phases. J Phys Chem Lett. 2018 Apr 19;9(8):1913-1919. doi: 10.1021/acs.jpclett.8b00549. Epub 2018 Apr 2. PMID:29595981

24.  Dickinson JM, D'Lugos AC, Naymik MA, Siniard AL, Wolfe AJ, Curtis DR, Huentelman MJ, Carroll CC. 2018. Transcriptome response of human skeletal muscle to divergent exercise stimuli. 2018. J Appl Physiol (1985). 2018 Jun 1;124(6):1529-1540. doi: 10.1152/japplphysiol.00014.2018. Epub 2018 Mar 15. PMID:29543133

25.  Filippova EV, Zemaitaitis B, Aung T, Wolfe AJ, Anderson WF. 2018. Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB. MBio. 2018 Feb 27;9(1). pii: e01993-17. doi: 10.1128/mBio.01993-17. PMID:29487239

26.  Miller-Ensminger T, Garretto A, Brenner J, Thomas-White K, Zambom A, Wolfe AJ, Putonti C. 2018. Bacteriophages of the Urinary Microbiome. J Bacteriol. 2018 Mar 12;200(7). pii: e00738-17. doi: 10.1128/JB.00738-17. Print 2018 Apr 1. PMID:29378882

27.  Price TK, Hilt EE, Dune TJ, Mueller ER, Wolfe AJ, Brubaker L. 2017. Urine trouble: should we think differently about UTI? Int Urogynecol J. 29(2):205-210 PMID:29279968

28.  Nakayasu ES, Burnet MC, Walukiewicz HE, Wilkins CS, Shukla AK, Brooks S, Plutz MJ, Lee BD, Schilling B, Wolfe AJ, Müller S, Kirby JR, Rao CV, Cort JR, Payne SH. 2017. Ancient Regulatory Role of Lysine Acetylation in Central Metabolism.MBio. 2017 Nov 28;8(6). pii: e01894-17. doi: 10.1128/mBio.01894-17. PMID:29184018

29.  Davis R, Écija-Conesa A, Gallego-Jara J, de Diego T, Filippova EV, Kuffel G, Anderson WF, Gibson BW, Schilling B, Canovas M, Wolfe AJ. 2018. An acetylatable lysine controls CRP function in E. coli. Mol Microbiol. 2018 Jan;107(1):116-131. doi: 10.1111/mmi.13874. Epub 2017 Nov 23. PMID:29105190

30.  Wolfe AJ, Si W, Zhang Z, Blanden AR, Hsueh YC, Gugel JF, Pham B, Chen M, Loh SN, Rozovsky S, Aksimentiev A, Movileanu L. 2017. Quantification of Membrane Protein-Detergent Complex Interactions. J Phys Chem B. 2017 Nov 9;121(44):10228-10241. doi: 10.1021/acs.jpcb.7b08045. Epub 2017 Oct 31. PMID:29035562

31.  Jacobs KM, Thomas-White KJ, Hilt EE, Wolfe AJ, Waters TP. 2017. Microorganisms Identified in the Maternal Bladder: Discovery of the Maternal Bladder Microbiota.AJP Rep. 2017 Jul;7(3):e188-e196. doi: 10.1055/s-0037-1606860. Epub 2017 Sep 29.PMID:28970961

32.  Dune TJ, Price TK, Hilt EE, Thomas-White KJ, Kliethermes S, Brincat C, Brubaker L, Schreckenberger P, Wolfe AJ, Mueller ER. 2017. Urinary Symptoms and Their Associations with Urinary Tract Infections in Urogynecologic Patients. Obstet Gynecol. 2017 Oct;130(4):718-725. doi: 10.1097/AOG.0000000000002239. PMID:28885414

33.  Losada L, Amundsen CL, Ashton-Miller J, Chai T, Close C, Damaser M, DiSanto M, Dmochowski R, Fraser MO, Kielb SJ, Kuchel G, Mueller ER, Parker-Autry C, Wolfe AJ, Mallampalli MP. Expert Panel Recommendations on Lower Urinary Tract Health of Women Across Their Life Span. J Womens Health (Larchmt). Nov;25(11):1086-1096. PMID:27285829

34.   Brubaker L, and Wolfe AJ. 2017. The Female Urinary Microbiota/Microbiome: Clinical and Research Implications. Rambam Maimonides Med J. Apr 28;8(2). PMID:28467757

35.  Brubaker  L, and Wolfe AJ. 2017. Year in Review 2016: The Female Urinary Microbiota. Nature Reviews Urology. 4(2):72-74. PMID:28050013
 

36. Mueller E, Wolfe AJ, and Brubaker L. 2017. The Female Urinary Microbiota. Current Op in Urology review. May;27(3):282-286. PMID:28234750
 

37. Brubaker L, and Wolfe AJ. 2017. The Female Urinary Microbiota, Urinary Health and Common Urinary Disorders. Annals of Translational Medicine. 5(2):34. PMID:28217699
 

38. Schwaderer  AL, and Wolfe AJ. 2017. The Association Between Bacteria and Urinary Stones. Annals of Translational Medicine. 5(2):32. PMID:28217697
 

39. Brubaker L and Wolfe AJ. 2016. The Urinary Microbiota: A Paradigm Shift for Bladder Disorders? Current Opinions in Obstretrics and Gynecology. Oct;28(5):407-12.
 

40. Losada L, Amundsen CL, Ashton-Miller J, Chai T, Close C, Damaser M, DiSanto M, Dmochowski R, Fraser MO, Kielb SJ, Kuchel G, Mueller ER, Parker-Autry C, Wolfe AJ, Mallampalli MP. Expert Panel Recommendations on Lower Urinary Tract Health of Women Across Their Life Span. J Womens Health (Larchmt). Nov;25(11):1086-1096. PMID:27285829
 

41.  Thomas-White K, Brady M, Wolfe AJ, Mueller ER. 2016. The Bladder is Not Sterile: History and Current Discoveries on the Urinary Microbiome. Curr Bladder Dysfunct Rep. Mar;11(1):18-24. Epub 2016 Jan 30. PMID:27182288

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