The Gomez-Simmonds Lab | UC Davis Health

The Gomez-Simmonds Lab

The Gomez-Simmonds lab in the Division of Infectious Diseases at UC Davis was established in August of 2024 with the goals of linking together the fields of bacterial genomics, clinical microbiology, and hospital epidemiology to conduct clinically-relevant, translational infectious diseases research.

Antimicrobial resistance has increasingly challenged our ability to successfully use antibiotics to treat infections and is now considered a critical threat to human health. Foremost among the pathogens of greatest concern are Enterobacterales and other Gram-negative bacteria that have acquired resistance to broad-spectrum beta-lactam antibiotics. These bacteria primarily infect hospitalized patients, where they are associated with worse clinical outcomes, prolonged hospital stays, and increased costs. However, proliferation of certain types of multidrug-resistant (MDR) bacteria (e.g. extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales) in the community has further heightened concern.

The main focus of our lab is to characterize the genomic epidemiology and mechanisms of resistance of multidrug-resistant (MDR) Gram-negative bacteria. Putting together whole genome sequencing, epidemiologic, and clinical data, we aim to determine how these bacteria evolve and disseminate within hospital settings. We have a particular interested in understanding the genetic context of antibiotic resistance genes and how plasmids and other mobile genetic elements contribute to their transmission. Current projects include using nanopore long-read sequencing for genomic surveillance and to detect hospital reservoirs for MDR Gram-negative bacteria and multidrug-resistance plasmids. We are also interested in determining how antibiotic resistance phenotypes are shaped by the presence of different genetic resistance determinants, and how we can best use whole genome sequencing and machine learning to develop genomic prediction models for antibiotic resistance. Ultimately, our long-term goal is to harness whole genome sequencing to optimize surveillance, infection control and prevention, and treatment strategies to mitigate the impact of these important pathogens.

Clinical and genomic epidemiology of ESBL-producing and carbapenem-resistant Gram-negative bacteria

  • The cornerstone of our laboratory’s work involves characterizing the population structure and mechanisms of resistance of MDR Gram-negative bacteria using molecular typing and whole genome sequencing. This work involves identifying and characterizing evolving bacterial strains and plasmids associated with the dissemination of antibiotic resistance genes as well as how they contribute to clinical outcomes. The goal of this research is to support surveillance efforts and inform treatment selection for antibiotic resistant infections.

Genetic factors associated with beta-lactam resistance in ESBL-producing Gram-negative bacteria

  • ESBL-producing Enterobacterales represent a serious public health threat because they are resistant to many beta-lactam antibiotics and have spread rapidly worldwide. Predicting antibiotic resistance using whole genome sequencing-based methods may enable rapid, culture-free identification of effective treatment options for multidrug-resistant bacteria. Using whole genome sequencing to comprehensively characterize bacterial genomes, our lab has been investigating how different genetic determinants contribute to antibiotic resistance in thse organisms and how to best account for them in genomic prediction models to improve model accuracy. 

Plasmids harboring broad-spectrum beta-lactam resistance genes 

  • An important focus of our research is investigating plasmid-mediated beta-lactamase genes in Gram-negative bacteria, including how plasmids contribute to the diversification and spread of CRE. The goals of this work are to determine the incidence of horizontal transfer of plasmids in the hospital, characterize the population structure of plasmid families associated with multispecies spread of beta-lactamase genes, and elucidate plasmid dynamics leading to the emergence of novel resistance phenotypes. 

Environmental reservoirs for MDR Gram-negative bacteria and resistance plasmids

  • Hospital environments are important contributors to the persistence and spread of MDR Gram-negative bacteria. Importantly, prior studies have demonstrated poor responsiveness of indirect transmission to enhanced infection control measures, signaling a need to better understand environmental transmission of these organism. Using whole genome sequencing, one of our goals is to determine how environmental colonization contributes to the spread of antibiotic resistance in the hospital.

Dr. Angela Gomez-Simmonds

Principal Investigator and Bug-Drug enthusiast

Kim Olsen

Lab Manager

Arena Shafeque, M.D.

Clinical Infectious Diseases Fellow

Nadia Burciaga

Undergraduate Student

Selected Recent Publications and Presentations:

  • Gomez-Simmonds A, Annavajhala MK, Seeram D, Hokunson TW, Park H, Uhlemann AC. Genomic epidemiology of carbapenem-resistant Enterobacterales at a New York City hospital over a ten-year period reveals complex plasmid-clone dynamics and evidence for frequent horizontal transfer of blaKPC. Genome Res. 2024:gr.279355.124. doi: 10.1101/gr.279355.124.
  • Hokunson TW*, Hernandez EM*, Annavajhala MK, Uhlemann AC, Gomez-Simmonds A (*contributed equally).  Genetic factors associated with piperacillin/tazobactam and cefepime resistance in clinical extended-spectrum beta-lactamase-producing Enterobacterales isolates from the intensive care unit. Poster, IDWeek 2024, Los Angeles CA.
  • Annavajhala MK, Hokunson TW, Uhlemann AC, Gomez-Simmonds A. Genomic surveillance of the hospital environment reveals persistence and spread of multidrug resistant Gram-negative bacteria and plasmids across two inpatient units. Poster, ASM 2024, Atlanta GA.
  • DeLaurentis C, Hokunson T, Nelson B, Annavajhala MK, Uhlemann AC, Gomez-Simmonds A. Piperacillin-Tazobactam or Cefepime for Treatment of Third Generation Cephalosporin Resistant Pneumonia in Intensive Care Unit Patients. Poster, IDWeek 2023, Boston MA.
  • Gomez-Simmonds A, Annavajhala MK, Tang N, Rozenberg FD, Ahmad M, Park H, Lopatkin AJ, Uhlemann AC. Population structure of blaKPC-harbouring IncN plasmids at a New York City medical centre and evidence for multi-species horizontal transmission. Journal of Antimicrobial Chemotherapy 2022;77:1873-1882. doi: 10.1093/jac/dkac114.
  • Zucker J*, Gomez-Simmonds A*, Purpura LJ, Shoucri S, LaSota E, Morley NE, Sovic BW, Castellon MA, Theodore DA, Bartram LL, Miko BA, Scherer ML, Meyers KA, Turner WC, Kelly M, Pavlicova M, Basaraba CN, Baldwin MR, Brodie D, Burkart KM, Bathon J, Uhlemann AC, Yin MT, Castor D*, Sobieszczyk ME* (*contributed equally). Supervised machine learning approach to identify early predictors of poor outcome in patients with COVID-19 presenting to a large quaternary care hospital in New York City. Journal of Clinical Medicine 2021;10:3523. doi: 10.3390/jcm10163523.
  • Gomez-Simmonds A, Annavajhala MK, McConville TH, Dietz DE, Shoucri SM, Laracy JC, Rozenberg FD, Nelson B, Greendyke WG, Furuya EY, Whittier S, Uhlemann AC. Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital. Journal of Antimicrobial Chemotherapy 2021;76:380-384. doi: 10.1093/jac/dkaa466.
  • Nelson BC, Laracy J, Shoucri S, Dietz D, Zucker J, Patel N, Sobieszczyk ME, Kubin CJ, Gomez-Simmonds A. Clinical outcomes associated with methylprednisolone in mechanically ventilated patients with COVID-19. Clinical Infectious Diseases 2021;72:e367-72. doi: 10.1093/cid/ciaa1163.
  • Gomez-Simmonds A, Annavajhala MK, McConville TH, Dietz DE, Shoucri SM, Laracy JC, Nelson B, Whittier S, Uhlemann AC. Cluster of carbapenemase-producing Enterobacterales secondary infections during the COVID-19 crisis at a New York City hospital. Poster, IDWeek 2020, Virtual.

Center for Immunology and Infectious Diseases, Room 2069

University of California, Davis

Email: agomezsimmonds@ucdavis.edu