Profiles
Alan J. Wolfe, PhD
Professor
Research Interests
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.
Publications
Primary Peer Reviewed Research, Reviews, Book Chapters, Commentaries,
and Editorials
Brubaker L, Gourdine J-PF, Siddiqui NY, Holland A, Halverson T, Limeria R, Pride D, Ackerman L, Forster CS, Jacobs KM, Thomas-White KJ, Putonti C, Dong Q, Weinstein M, Lukacz ES, Karstens L, Wolfe AJ. Forming consensus to advance urobiome research. mSystems 6:e01371-20. https://doi.org/10.1128/mSystems.01371-20.
Hoffman C, Siddiqui NY, Fields I, Gregory WT, Simon HM, Mooney MA, Wolfe AJ, Karstens L.mSystems. 2021, Species-Level Resolution of Female Bladder Microbiota from 16S rRNA Amplicon Sequencing. Sep 14:e0051821. doi: 10.1128/mSystems.00518-21. Online ahead of print.PMID: 34519534
Gilbert NM, Choi B, Du J, Collins C, Lewis AL, Putonti C, Wolfe AJ. 2021. A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection. Biol Open. 2021 Aug 15;10(8):bio058931. doi: 10.1242/bio.058931. Epub 2021 Aug 13. PMID: 3438731
Kachroo N, Lange D, Penniston KL, Stern J, Tasian G, Bajic P, Wolfe AJ, Suryavanshi M, Ticinesi A, Meschi T, Monga M, Miller AW. 221. Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition. mBio. 2021 Aug 10:e0200721. doi: 10.1128/mBio.02007-21. Online ahead of print. PMID: 34372696
Abdul-Rahim O, Wu Q, Price TK, Pistone G, Diebel K, Bugni TS, Wolfe AJ. 2021. Phenyl-lactic acid is an active ingredient in bactericidal supernatants of Lactobacillus crispatus. J Bacteriol. 2021 Jul 19:JB0036021. doi: 10.1128/JB.00360-21. Online ahead of print. PMID: 34280003
Barnes HC, Wolff B, Abdul-Rahim O, Harrington A, Hilt EE, Price TK, Halverson T, Hochstedler BR, Pham T, Acevedo-Alvarez M, Joyce C, Fitzgerald CM, Schreckenberger PC, Brubaker L,Wolfe AJ, Mueller ER. 2021. A Randomized Clinical Trial of Standard Versus Expanded Cultures to Diagnose Urinary Tract Infections in Women. .J Urol. 2021 Jun 29:101097JU0000000000001949. doi: 10.1097/JU.0000000000001949. Online ahead of print. PMID: 34184930
Mormando R,Wolfe AJ, Putonti C. 2021. Discriminating between JCPyV and BKPyV in Urinary Virome Data Sets. . May 31;13(6):1041. doi: 10.3390/v13061041.PMID: 34072839
Zandbergen LE, Halverson T, Brons JK, Wolfe AJ, de Vos MG. 2021. The Good and the Bad: Ecological Interaction Measurements Between the Urinary Microbiota and Uropathogens. J.Front Microbiol. May 10;12:659450. doi: 10.3389/fmicb.2021.659450. eCollection 2021.PMID: 34040594.
Burnett LA, Hochstedler BR, Weldon K, Wolfe AJ, Brubaker L. 2021. Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women. .Neurourol Urodyn. 2021 May 26. doi: 10.1002/nau.24707. Online ahead of print.PMID: 34036621
Putonti C, Thomas-White K, Crum E, Hilt EE, Price TK, Wolfe AJ. 2021. Genome Investigation of Urinary GardnerellaStrains and Their Relationship to Isolates of the Vaginal Microbiota. .mSphere. May 12;6(3):e00154-21. doi: 10.1128/mSphere.00154-21.PMID: 33980674
Hochstedler BR, Burnett L, Price TK, Jung C,Wolfe AJ, Brubaker L. 2021. Urinary microbiota of women with recurrent urinary tract infection: collection and culture methods. Int Urogynecol J. 2021 Apr 14. doi: 10.1007/s00192-021-04780-4. Online ahead of print PMID:
Kachroo N, Lange D, Penniston KL, Stern J, Tasian G, Bajic P,Wolfe AJ, Suryavanshi M, Ticinesi A, Meschi T, Monga M, Miller AW. 2021. Standardization of microbiome studies for urolithiasis: an international consensus agreement. Nat Rev Urol. 2021 Mar 29. doi: 10.1038/s41585-021-00450-8. PMID: 33782583
Brubaker L, Putonti C, Dong Q, Wolfe AJ. The human urobiome. Mamm Genome. 2021 Mar 2. doi: 10.1007/s00335-021-09862-8. Online ahead of print. PMID: 33651197
Ene A, Miller-Ensminger T, Mores CR, Giannattasio-Ferraz S,Wolfe AJ, Abouelfetouh A, Putonti C. 2021. Examination of Staphylococcus aureus Prophages Circulating in Egypt. 2021 Feb 22;13(2):337. doi: 10.3390/v13020337. PMID: 33671574
Mores CR, Price TK, Wolff B, Halverson T, Limeira R, Brubaker L, Mueller ER, Putonti C, Wolfe AJ. 2021. Genomic relatedness and clinical significance of Streptococcus mitisstrains isolated from the urogenital tract of sexual partners. Microb Genom. 2021 Feb 25. doi: 10.1099/mgen.0.000535. Epub 2021 Feb 25. PMID: 33629947
Bajic P, Wolfe AJ. 2021. The Microbiome of Male Infertility: Paving the Road Ahead. Eur Urol. 16:S0302-2838(21)00093-2. doi:10.1016/j.eururo.2021.02.009 PMID: 33608155
Écija-Conesa A, Gallego-Jara J, Lozano Terol G, Browning DF, Busby SJW, Wolfe AJ, Cánovas Díaz M, de Diego Puente T. 2020. An ideal spacing is required for the control of Class II CRP-dependent promoters by the status of CRP K100. FEMS Microbiol Lett. 2020 Nov 11;367(20):fnaa164. doi:10.1093/femsle/fnaa164.PMID: 33095239
Garretto A, Miller-Ensminger T, Ene A, Merchant Z, Shah A, Gerodias A, Biancofiori A, Canchola S, Canchola S, Castillo E, Chowdhury T, Gandhi N, Hamilton S, Hatton K, Hyder S, Krull K, Lagios D, Lam T, Mitchell K, Mortensen C, Murphy A, Richburg J, Rokas M, Ryclik S, Sulit P, Szwajnos T, Widuch M, Willis J, Woloszyn M, Brassil B, Johnson J, Mormando R, Maskeri L, Batrich M, Stark N, Shapiro JW, Montelongo Hernandez C, Banerjee S, Wolfe AJ and Putonti C. 2020 Genomic Survey of coli From the Bladders of Women With and Without Lower Urinary Tract Symptoms Frontiers in Microbiology 11:2094 doi: 10.3389/fmicb.2020.02094
Zamora M, Ziegler CA, Freddolino PL, Wolfe AJ. A Thermosensitive, Phase-Variable Epigenetic Switch: pap Revisited. September 2020 Volume 84 Issue 3 e00030-17 DOI:10.1128/MMBR.00030-17.
Putonti C, Shapiro JW, Ene A, Tsibere O, Wolfe AJ. 2020. Comparative genomic study of Lactobacillus jensenii and the newly defined Lactobacillus mulieris species identifies species-specific functionality. mSphere. 5(4):e00560-20. doi: 10.1128/mSphere.00560-20. PMID: 32817455
Wolfe AJ, Brubaker L. 2020. ‘Ur-ine Old Age: Urinary Microbiome of Older Community Dwelling Women. Cell Host Microbe. 2020 Aug 12;28(2):149-151. doi: 10.1016/j.chom.2020.07.012.PMID: 32791105
Vollstedt A, Baunoch D, Wolfe A, Luke N, Wojno KJ, Cline K, Belkoff L, Milbank A, Sherman N, Haverkorn R, Gaines N, Yore L, Shore N, Opel M, Korman H, Kelly C, Jafri M, Campbell M, Keating P, Hazelton D, Makhlouf B, Wenzler B, Sabry M, Burks F, Penaranda M, Smith DE, Cacdac P, Sirls L. 2020. Bacterial Interactions as Detected by Pooled Antibiotic Susceptibility Testing (P-AST) in Polymicrobial Urine Specimens. Journal of Surgical Urology. J Sur urology: JSU-101. DOI: 10.29011/JSU-101.100001
Christensen DG, Xie X, Basisty N, Byrnes J, McSweeney S, Schilling B, Wolfe AJ. 2019. Posttranslational Protein Acetylation: An elegant Mechanism for Bacteria to Dynamically Regulate Metabolic Functions. Front Microbiol. 2019 Jul 12;10:1604. doi: 10.3389/fmicb.2019.01604. eCollection 2019. PMC6640162.
Miller-Ensminger T, Mormando R, Maskeri L, Shapiro JW, Wolfe AJ, Putonti C. Introducing Lu-1, a Novel Lactobacillus jensenii Phage Abundant in the Urogenital Tract. PLoS One. 2020 Jun 11;15(6):e0234159. doi: 10.1371/journal.pone.0234159. eCollection 2020.PMID: 32525961
Price TK, Lin H, Gao X, Thomas-White KJ, Hilt EE, Mueller ER, Wolfe AJ, Dong Q, Brubaker L. Bladder Bacterial Diversity Differs In Continent and Incontinent Women: A Cross-Sectional Study. Am J Obstet Gynecol. 2020 May 4:S0002-9378(20)30512-3. doi: 10.1016/j.ajog.2020.04.033.
Highlighted in Urotoday’s Beyond the Abstract
Price TK, Wolff B, Halverson T, Limeira R, Brubaker L, Dong Q, Mueller ER, Wolfe AJ. Temporal Dynamics of the Adult Female Lower Urinary Tract Microbiota. mBio. 2020 Apr 21;11(2):e00475-20. doi: 10.1128/mBio.00475-20.PMID: 32317321
Brassil B, Mores CR, Wolfe AJ, Putonti C. 2020. Characterization and Isolation of Temperate Streptococcus anginosus phages from the Urinary Tract. Journal of General Virology. Apr 21. doi: 10.1099/jgv.0.001407. [Epub ahead of print] PMID:32310742
Hilt EE, Putonti C, Thomas-White K, Lewis AL, Visick KL, Gilbert NM, Wolfe AJ. Aerococcus urinae isolated from women with lower urinary tract symptoms: in vitro aggregation and genome analysis. J Bacteriol. 2020 Apr 13. pii: JB.00170-20. doi: 10.1128/JB.00170-20. [Epub ahead of print] PMID:32284319
Highlighted in Urotoday’s Beyond the Abstract
Jacobs KM, Price TK, Thomas-White K, Halverson T, Davies A, Myers DL, Wolfe AJ. Cultivable Bacteria in Urine of Women With Interstitial Cystitis: (Not) What We Expected. Female Pelvic Med Reconstr Surg. 2020 Apr 6. doi: 10.1097/SPV.0000000000000854. [Epub ahead of print] PMID:32265402
Chen YB, Hochstedler B, Pham TT, Acevedo Alvarez M, Mueller ER, Wolfe AJ. The Urethral Microbiota - A Missing Link in the Female Urinary Microbiota. J Urol. 2020 Mar 2:101097JU0000000000000910. doi: 10.1097/JU.0000000000000910. [Epub ahead of print] PMID:32118507
Wolff BJ, Price TK, Joyce CJ, Wolfe AJ, Mueller ER. 2019. Oral probiotics and the female urinary microbiome: a double-blinded randomized placebo-controlled trial. Int Urol Nephrol. Dec;51(12):2149-2159. doi: 10.1007/s11255-019-02282-3. Epub 2019 Sep 18. PMID:31535332
Jung CE, Chopyk J, Shin JH, Lukacz ES, Brubaker L, Schwanemann LK, Knight R, Wolfe AJ, Pride DT. 2019. Benchmarking urine storage and collection conditions for evaluating the female urinary microbiome. Sci Rep. 2019 Sep 16;9(1):13409. doi: 10.1038/s41598-019-49823-5. PMID:31527753
Price TK, Hilt EE, Thomas-White K, Mueller ER, Wolfe AJ, Brubaker L. 2019. The urobiome of continent adult women: a cross-sectional study. BJOG. an;127(2):193-201. doi: 10.1111/1471-0528.15920. Epub 2019 Oct 9. PMID:31469215
Karstens L., Asquith M, Davin S, Fair D, Gregory WT, Wolfe AJ, Braun J, McWeeney S. 2019. Controlling for contaminants in low biomass 16S rRNA gene sequencing experiments. mSystems. 2019 Jun 4;4(4). pii: e00290-19. doi: 10.1128/mSystems.00290-19. PMC6550369.
Dornbier RA, Bajic P, Van Kuiken M, Jardaneh A, Lin H, Gao X, Knudsen B, Dong Q, Wolfe AJ, Schwaderer AL. 2019. The microbiome of calcium-based urinary stones. Urolithiasis. 2019 Jun 25. doi: 10.1007/s00240-019-01146-w. [Epub ahead of print] PMID:31240349
Filippova EV, Weigand,S, Kiryukhina, O, Wolfe AJ, Anderson WF. 2019. Analysis of crystalline and solution states of ligand-free spermidine N-acetyltransferase (SpeG) from Escherichia coli. Acta Cryst. D. 2019 Jun 1;75(Pt 6):545-553. doi: 10.1107/S2059798319006545. Epub 2019 May 28. PMC6580228.
Garretto A, Miller-Ensminger T, Wolfe AJ, Putonti C. 2019. Bacteriophages of the Lower Urinary Tract. Nature Reviews Urology 2019 May 9. doi: 10.1038/s41585-019-0192-4. [Epub ahead of print] PMID:31073244
Dornbier R, Bajic P, Wolfe AJ, Schwaderer A. 2019. The Role of Bacteria in Non-infection Stone Formation. In The Role of Bacteria in Urology. BH Chew and D Lange (ed) Springer.
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