Ana Lidia Flores-Mireles Hawk Assistant Professor

Research Interests:

Catheter-associated urinary tract infections (CAUTIs) are the most common cause of healthcare associated infection (HAI) worldwide, accounting for 40% of all HAIs with more than one million cases diagnosed annually in hospitals and nursing homes in the United States and Europe and it accounts for an annual cost of $340–370 million. Importantly, CAUTI often leads to secondary bloodstream infection with a seven day mortality rate of more than 30%. This becomes more troublesome since urinary catheters use is exceedingly common in health care facilities and it is estimated that 20-50% of all hospitalized patients receive a urinary catheter, which accounts for >30 million Foley catheters inserted annually in the United States, resulting in 1 million CAUTIs. The presence of a urinary catheter changes the bladder environment allowing several pathogens such as Enterococcus spp., Staphylococcus aureus, Candida spp., Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Group B Streptococcus, to colonize the bladder, something that otherwise would not occur (22, 23). From these groups of bacteria, Enterococcus spp. are the leading cause of CAUTI, have emerged as a frequent cause of HAIs, and their treatment are increasingly challenging due to their intrinsic and acquired resistance to antibiotics. Currently, 30% of all enterococcal HAI isolates are resistant to vancomycin, leading the CDC to classify VRE as a serious threat, recommending monitoring and the development of new therapeutic strategies. My lab is interested in understanding how urinary catheterization-induced inflammation renders the host susceptible to microbial infection of the urinary tract and subsequent dissemination. My lab is also interested in deciphering key host and pathogen determinants for infection and targeting them to develop novel antibiotic-sparing therapies.

Biography:

• Assistant Professor, Department of Biological Sciences, University of Notre Dame, Notre Dame, IN  2018 – Present
• Staff Research Scientist, Molecular Microbiology Department, Washington University School of Medicine, St. Louis, MO  2017 – 2018
• Postdoctoral Researcher, Molecular Microbiology Department, Washington University School of Medicine, St. Louis, MO  2012 – 2017
• PhD, Microbiology, Cornell University, Ithaca, NY  2011

Selected Publications:

• La Bella, A^@#., Andersen, A. J^@#., Gervais, N.C., Molina, J. J^@#., Molesan, A^#., Stuckey, P.V^@#., , Wensing, L., Nobile, C.J., Shapiro, R. S., Santiago-Tirado, F.H^#%., and Flores-Mireles, A. L^#%. 2023. The catheterized bladder environment promotes Efg1- and Als1-dependent Candida albicans infection. Science Advances. 3 Mar 2023. Vol 9, Issue 9. DOI: 10.1126/sciadv.ade7689 ^%Corresponding authors. IF: 14.14. Citations: 0.
• Nye, T.M. Tukenmez, H., Singh, P., Flores-Mireles AL^#, Obernuefemann C, Pinkner J, Sarkar, S., Bonde M, Lindgren A. E. G., Dodson, K. W., Johansson, J., Almqvist F, Caparon MG, Hultgren SJ. 2022. Ring-fused 2-pyridones effective against multidrug-resistant Gram-positive pathogens and synergistic with standard-of-care antibiotics. PNAS. 119(43):e2210912119. doi: 10.1073/pnas.2210912119. IF: 12.78. Citations: 0.
• Gervais, N.C., La Bella, A^@#., Wensing, L., Sharma, J., Acquaviva, V., Best, M., Cardena Lopes, R. O., Fogal, M., Uthayakumar, D., Chavez, A., Santiago-Tirado, F.H^#. Flores-Mireles, A. L^#, and Shapiro, R. S. 2022. Development and applications of a CRISPR activation system for facile genetic overexpression in Candida albicans. G3: Genes|Genomes|Genetics. 2023 Feb 9; 13(2):jkac301. doi: 10.1093/g3journal/jkac301. IF: 3.154. Citations: 0.
• Andersen, A. J^@#., Fong, J., La Bella, A^@#., Molina, J.J^@#., Molesan, A^#., Champion, M^#., Howell, C., and Flores-Mireles, A. L^#%. 2022.  Inhibiting host-protein deposition on urinary catheters reduces associated urinary tract infections. Elife. 2022 Mar 29;11:e75798. doi: 10.7554/eLife.75798. PMID: 35348114. ^%Corresponding author. IF: 8.713. Citations: 11.
  • Featured on “This Week in Microbiology” podcast sponsored by American Society of America.
  • Highlighted by Notre Dame College of Science, University of Notre Dame.
  • Highlighted in Immunology and Microbiology by Technology Networks. European magazine
  • Highlighted in NS Medical Devices magazine. March 15, 2022.
• Lam, L.N., Brunson, D. N., Molina, J.J^@#., Flores-Mireles, A.L. ^#, and Lemos, J. A. 2022.  The AdcACB/AdcAII system is Essential for Zinc Homeostasis and an Important Contributor of Enterococcus faecalis Virulence. Virulence. Dec;13(1):592-608. doi:10.1080/21505594.2022.2056965. PMID: 35341449. IF: 5.542. Citations: 3.
• Kundra, S., Lam, L.N., Kajfasz, J.K. Casella, L. G, Andersen, M.J ^@#., Abraches, J., Flores-Mireles, A.L. ^#%, and Lemos, J. A. 2021.  c-di-AMP is essential for the virulence of Enterococcus faecalis. Infect Immun. 2021 Oct 15;89(11):e0036521. doi: 10.1128/IAI.00365-21. Epub 2021 Aug 23.     PMID: 34424750. ^%Co-corresponding author. IF: 3.609. Citations: 6.
•  Vu HM⁺, Hammers D^@#, Liang, Nguyen GL^#, Benz ME^#, Moran T^@#, Higashi DL, Park CL, Ayinuola YA^#, Donahue DL^#, Flores-Mireles AL^#, Ploplis VA^#, Castellino FJ^# and Lee S^#. 2021. Group A Streptococcus-induced activation of human plasminogen is required for keratinocyte wound retraction and rapid clot dissolution. Frontiers in Cardiovascular Medicine- Thrombosis. June 10, 2121.  IF = 6.05. Citations = 4.
• Chambers JM^@#, Addiego A^#, Flores-Mireles AL^#, Wingert RA^#. 2020. Ppargc1a Controls Ciliated Cell Development by Regulating Prostaglandin Biosynthesis. Cell Rep. 2020 Nov 10;33(6):108370. doi: 10.1016/j.celrep.2020.108370. IF = 9.995. Citations = 13.
• Gaston, J., Andersen, MJ^@#., Johnson, A., White, A., Humby, M., Brauer, A., Learman, B., Flores-Mireles AL^#%. and C. E. Armbruster^%. 2020. Proteus mirabilis and Enterococcus faecalis persistently co-colonize the catheterized urinary tract and form recalcitrant polymicrobial biofilms with altered biofilm architecture. Pathogens.  IF = 4.41. Citations = 25. ^% Co-corresponding author.
• Russo B^@#, Ayinuola YA^#, Singh D^#, Carothers K^@#, Fischetti VA, Flores-Mireles AL^#., Lee SW^#, Ploplis VA^#, Liang Z^#, Castellino FJ^#. 2020. The M-protein of Streptococcus pyogenes strain AP53 retains cell surface functional plasminogen binding after inactivation of the sortase A gene. J Bacteriol. 2020 Mar 72. doi: 10.1128/JB.00096-20. PubMed PMID: 32123038. IF = 3.49. Citations = 8.
• Mursalin, H., Coburn, P.S., Livingston, E.T., Miller, F.C., Astley, R., Flores-Mireles, A.L^#. and Callegan, M. C. 2020. Bacillus S-Layer-Mediated Innate Interactions During Endophthalmitis. Front. Immunol. 12 February 2020 | https://doi.org/10.3389/fimmu.2020.00215 .  IF = 6.429. Citations = 15.
• Andersen, A. J^@#., and Flores-Mireles, A. L^#%. 2020. Urinary Catheter Coating Modifications: The Race against Catheter-Associated Infections. Coatings 2020, 10(1), 23. IF = 3.12. Citations = 50. ^% Corresponding author.
• Flores-Mireles, A. L. 2019^#. mSphere of Influence: Uncovering new ways to control multidrug resistances by dissecting essential cell processes. mSphere 4, e00648-00619, doi:10.1128/mSphere.00648-19. IF = 4.17. Citations = 2. ^% Corresponding author.
• Flores-Mireles, A. L^#%., Hreha, T. N., and Hunstad, D. A. 2019. Pathophysiology, treatment, and prevention of catheter-associated urinary. Topics in Spinal cord injury. 25(3):228-240. doi: 10.1310/sci2503-228. IF = 2.9. Citations = 98. ^%Corresponding author.
•  Colomer-Winter C, Lemos, J.A., and Flores-Mireles, A.L^#%. 2019. Biofilm assays on fibrinogen-coated silicone catheters and 96-well polystyrene plates. BioProtocols. 9(6). IF = 5.78. Citations = 30. ^%Corresponding author
• Walker J. N., Flores-Mireles, A. L. ^#*, Lynch, A.J.L., Pinkner, C., Caparon, M.G., Hultgren, S.J., and Desai, A. 2019. High Resolution Imaging Reveals Microbial Biofilms on Patient Urinary Catheters Despite Antibiotic Administration. World in Journal of Urology. 2019 Dec 2. doi: 10.1007/s00345-019-03027-8. IF = 2.981. Citations = 21.
  • * Co-lead author C. C.W. and A. L. F-M. equal contribution
• Colomer-Winter C, Flores-Mireles AL*, Kundra, S., Hultgren SJ and Lemos JA. 2019. (p)ppGpp and CodY promote Enterococcus faecalis virulence in a murine model of catheter-associated urinary tract infection. mSphere. 24;4(4):e00392-19. doi: 10.1128/mSphere.00392-19. IF = 4.17. Citations = 17.
  •  * Co-lead author C. C.W. and A. L. F-M. equal contribution
• Westfall, C., Flores-Mireles, A. L*, Robinson, J.I., Lynch, A. J. L., Hultgren, S., Henderson, J.P., Levin. P. A. 2019. The widely used antimicrobial triclosan induces high levels of antibiotic tolerance in vitro and reduces antibiotic efficacy up to 100-fold in vivo.  Antimicrobial Agents and Chemotherapy. 63(5). IF = 5.938. Citations = 64.
  •  * Co-lead author C. W. and A. L. F-M. equal contribution.
  • Highlighted by Record, the Washington University News Letter.
  • Highlighted by European magazine, Healthcare-in-Europe
  • Highlighted by GenBio, Science Daily and other magazines
  • Highlighted by St Louis Public Radio
• Di Venanzio, G., Flores-Mireles, A.L., Calix, J., Haurat, F. M., Scott, N., Palmer, L., Potter, R., Hibbing, M., Friedman, L., Wang, B., Dantas, G., Skaar, E., Hultgren, S. J., and Feldman, M. 2019. Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes. Nature Communication. Jun 24;10(1):2763. IF = 17.69. Citations = 64.  
• Colomer-Winter C, Flores-Mireles AL Baker SP, Frank KL, Lynch AJL, Hultgren SJ, Kitten T and Lemos JA. 2018. Manganese acquisition is essential for virulence of Enterococcus faecalis. PLOS Pathogens. 14(9). IF = 7.464. Citations = 62.
  • Nature Chemical Biology wrote a commentary on this work titled “Metal Enterococcus equipment” and selected as a researcher highlight in November 2018 issue.
  • Highlighted in Phy@Org
  • Highlighted in Science Daily
• Shen J, Walsh BJC, Flores-Mireles AL, Peng H, Zhang Y, Zhang Y, Trinidad JC, Hultgren SJ, Giedroc DP. 2018. Hydrogen Sulfide Sensing through Reactive Sulfur Species (RSS) and Nitroxyl (HNO) in Enterococcus faecalis. ACS Chem Biol. 2018 Jun 15;13(6):1610-1620. doi: 10.1021/acschembio.8b00230. IF = 4.634. Citations = 27.