Chelsie E. Armbruster PhD
Chelsie E. Armbruster
PhD
Assistant Professor
Department of Microbiology and Immunology
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Bacterial Pathogenesis; Infectious Disease; Microbial Pathogenesis; Microbiology
Professional Summary:
My laboratory is broadly focused on investigating microbe-microbe interactions, host-microbe interactions, and patient characteristics that influence disease severity. Our primary disease model is catheter-associated urinary tract infection (CAUTI), one of the most common healthcare-associated infections worldwide. Long-term use of indwelling catheters, which is common for management of certain conditions particularly in aging populations, results in continuous urine colonization by bacteria (bacteriuria) and can lead to infections of the bladder (cystitis), kidneys (pyelonephritis), and bloodstream (bacteremia).
My lab uses a combination of basic science and patient-oriented research, with the long-term goals of 1) identifying the uropathogen(s) most likely to cause symptomatic infection and adverse outcomes in patients, 2) utilizing an experimental model of infection to identify key virulence factors of these organisms, and 3) developing inhibitors of the identified virulence factors to reduce colonization and infection severity in vulnerable patient populations. As bacteriuria and CAUTI are frequently polymicrobial, which can influence the progression of the infection and the efficacy of antibiotic therapy, a major emphasis of this work is on understanding the contribution of polymicrobial colonization and microbe-microbe interactions to infection progression.
We recently identified the Gram-negative bacterium Proteus mirabilis as the most common cause of CAUTI in a cohort of nursing home residents, including cases of polymicrobial infection. P. mirabilis is well-known for its potent urease enzyme, which produces ammonia from the hydrolysis of urea in urine and leads to high urine pH, precipitation of polyvalent ions, and formation of urinary stones (urolithiasis). We determined that P. mirabilis urease activity can be modulated by other uropathogens in vitro and in vivo, contributing to the degree of tissue damage and risk of bacteremia. Enhancement of urease activity occurs with numerous isolates of P. mirabilis during co-culture with most of the other common uropathogens, including Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumoniae, while Morganella morganii dampens urease activity. Therefore, one project in the lab focuses on defining the underlying mechanism(s) of urease activity modulation and determining its potential as a therapeutic target.
Another focus of the lab is utilizing genome-wide screens to uncover new genes that contribute to pathogenesis during both monomicrobial and polymicrobial infection. We are using transposon insertion-site sequencing (Tn-Seq) to identify the full potential arsenal of P. mirabilis fitness and virulence factors during experimental CAUTI, including core factors that contribute to pathogenicity under all infection conditions tested, and accessory factors that are only required under certain infection conditions.
Education and Training:
- PhD, Microbiology and Immunology, Wake Forest University School of Medicine (2011)
- BS, Biotechnology, Rochester Institute of Technology, Honors (2007)
Employment:
- Assistant Professor, Microbiology and Immunology, State University of New York at Buffalo (2017-present)
- Research Investigator, Microbiology and Immunology, University of Michigan Medical School (2016–2017)
- Post Doctoral Fellow, Microbiology and Immunology, University of Michigan Medical School (2011–2016)
- Graduate Student, Microbiology and Immunology, Wake Forest University School of Medicine (2007–2011)
Awards and Honors:
- American Society for Microbiology Travel Award (2014)
- University of Michigan Department of Microbiology and Immunology Travel Award (2013)
- Mid-Atlantic Microbial Pathogenesis Meeting Travel Award (2011)
- Gordon A. Melson Outstanding Student Award Nominee/Runner-up (2011)
- NIH National Graduate Student Research Festival Travel Award (2010)
- CAP Student Travel Award (2009)
- Best Poster Award (2009)
- Outstanding Undergraduate Scholar (2006)
- Honors Program Scholarship (2004)
- Presidential Merit Scholarship (2003)
Research Expertise:
- Bacterial pathogens: Proteus mirabilis, Providencia stuartii, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis
- Motility: Swimming and swarming
- Polymicrobial infections: Urinary tract infection (UTI), catheter-associated urinary tract infection (CAUTI), bacteremia, otitis-media
- Urease: Enzymatic activity during co-culture of uropathogens, and contribution to pathogenesis
Grants and Sponsored Research:
- September 2019–May 2024
Conserved Proteus mirabilis genetic requirements for colonization of the catheterized urinary tract
National Institute of Diabetes and Digestive and Kidney Diseases
Role: Principal Investigator
$1,684,580 - June 2020–May 2022
Genetic susceptibility to mucosal infections with aging
NIAID-R21
Role: Co-Principal Investigator
$438,625 - September 2015–August 2017
Pathogenesis of Polymicrobial Catheter-Associated Urinary Tract Infection
National Institute of Diabetes and Digestive and Kidney Diseases
Role: Principal Investigator
$194,400 - August 2016–July 2017
Influence of aging on Proteus mirabilis urinary tract infection
University of Michigan Geriatrics Center
Role: Principal Investigator
$40,000 - June 2012–May 2015
Proteus mirabilis swarming: Initiation and role during urinary tract infection
National Institute of Allergy and Infectious Diseases
Role: Principal Investigator
$156,498 - April 2014–October 2014
Synergistic urease activity in polymicrobial catheter-associated urinary tract infections
University of Michigan Grants and Awards Program
Role: Co-Investigator
$12,360
Journal Articles:
- Armbruster CE, Forsyth-DeOrnellas V, Johnson AO, Smith SN, Zhao L, Wu W, Mobley HLT. Genome-wide transposon mutagenesis of Proteus mirabilis: Essential genes, fitness factors for catheter-associated urinary tract infection, and the impact of polymicrobial infection on fitness requirements. PLoS Pathog. 2017; 13(6).
- Armbruster CE, Smith SN, Johnson AO, DeOrnellas V, Eaton KA, Yep A, Mody L, Wu W, Mobley HL. The Pathogenic Potential of Proteus mirabilis Is Enhanced by Other Uropathogens during Polymicrobial Urinary Tract Infection. Infect Immun. 2017; 85(2).
- Armbruster CE, Prenovost K, Mobley HL, Mody L. How Often Do Clinically Diagnosed Catheter-Associated Urinary Tract Infections in Nursing Homes Meet Standardized Criteria? J Am Geriatr Soc. 2017; 65(2).
- Gaston JR, Andersen MJ, Johnson AO, Bair KL, Sullivan CM, Guterman LB, White AN, Brauer AL, Learman BS, Flores-Mireles AL, Armbruster CE. Enterococcus faecalis Polymicrobial Interactions Facilitate Biofilm Formation, Antibiotic Recalcitrance, and Persistent Colonization of the Catheterized Urinary Tract. Pathogens. 2020; 9(10).
- Brauer AL, Learman BS, Armbruster CE. Ynt is the primary nickel import system used by Proteus mirabilis and specifically contributes to fitness by supplying nickel for urease activity. Mol Microbiol. 2020.
- Johnson AO, Forsyth V, Smith SN, Learman BS, Brauer AL, White AN, Zhao L, Wu W, Mobley HLT, Armbruster CE. Transposon Insertion Site Sequencing of Providencia stuartii: Essential Genes, Fitness Factors for Catheter-Associated Urinary Tract Infection, and the Impact of Polymicrobial Infection on Fitness Requirements. mSphere. 2020; 5(3).
- Learman BS, Brauer AL, Eaton KA, Armbruster CE. A Rare Opportunist, Morganella morganii, Decreases Severity of Polymicrobial Catheter-Associated Urinary Tract Infection. Infect Immun. 2019; 88(1).
- Armbruster CE, Forsyth VS, Johnson AO, Smith SN, White AN, Brauer AL, Learman BS, Zhao L, Wu W, Anderson MT, Bachman MA, Mobley HLT. Twin arginine translocation, ammonia incorporation, and polyamine biosynthesis are crucial for Proteus mirabilis fitness during bloodstream infection. PLoS Pathog. 2019; 15(4).
- Brauer AL White AN Learman BS Johnson AO Armbruster CE. d-Serine Degradation by Proteus mirabilis Contributes to Fitness during Single-Species and Polymicrobial Catheter-Associated Urinary Tract Infection.. mSphere. 2019; 4(1).
- Forsyth VS, Mobley HLT, Armbruster CE. Transposon Insertion Site Sequencing in a Urinary Tract Model. Methods Mol Biol. 2019; 2021.
- Smith SN, Armbruster CE. Indwelling Urinary Catheter Model of Proteus mirabilis Infection. Methods Mol Biol. 2019; 2021.
- Armbruster CE. Testing the Ability of Compounds to Induce Swarming. Methods Mol Biol. 2019; 2021.
- Pang B, Armbruster CE, Foster G, Learman BS, Gandhi U, Swords WE. Autoinducer 2 (AI-2) Production by Nontypeable Haemophilus influenzae 86-028NP Promotes Expression of a Predicted Glycosyltransferase That Is a Determinant of Biofilm Maturation, Prevention of Dispersal, and Persistence In Vivo. Infect Immun. 2018; 86(12).
- Armbruster CE, Smith SN, Mody L, Mobley HLT. Urine cytokine and chemokine levels predict urinary tract infection severity independent of uropathogen, urine bacterial burden, host genetics, and host age. Infect Immun. 2018.
- Forsyth VS, Armbruster CE, Smith SN, Pirani A, Springman AC, Walters MS, Nielubowicz GR, Himpsl SD, Snitkin ES, Mobley HLT. Rapid Growth of UropathogenicEscherichia coliduring Human Urinary Tract Infection. MBio. 2018; 9(2).
- Forsyth VS, Armbruster CE, Smith SN, Pirani A, Springman AC, Walters MS, Nielubowicz GR, Himpsl SD, Snitkin ES, Mobley HLT. Rapid Growth of Uropathogenic Escherichia coli during Human Urinary Tract Infection. MBio. 2018; 9(2).
- Armbruster CE, Mobley HLT, Pearson MM. Pathogenesis of Proteus mirabilis Infection. EcoSal Plus. 2018; 8(1).
- Juneau RA, Pang B, Armbruster CE, Murrah KA, Perez AC, Swords WE. Peroxiredoxin-glutaredoxin and catalase promote resistance of nontypeable Haemophilus influenzae 86-028NP to oxidants and survival within neutrophil extracellular traps. Infect Immun. 2015; 83(1).
- Armbruster CE, Hodges SA, Smith SN, Alteri CJ, Mobley HL. Arginine promotes Proteus mirabilis motility and fitness by contributing to conservation of the proton gradient and proton motive force. Microbiologyopen. 2014; 3(5).
- Armbruster CE, Smith SN, Yep A, Mobley HL. Increased incidence of urolithiasis and bacteremia during Proteus mirabilis and Providencia stuartii coinfection due to synergistic induction of urease activity. J Infect Dis. 2014; 209(10).
- Armbruster CE, Hodges SA, Mobley HL. Initiation of swarming motility by Proteus mirabilis occurs in response to specific cues present in urine and requires excess L-glutamine. J Bacteriol. 2013; 195(6).
- Armbruster CE, Pang B, Murrah K, Juneau RA, Perez AC, Weimer KE, Swords WE. RbsB (NTHI_0632) mediates quorum signal uptake in nontypeable Haemophilus influenzae strain 86-028NP. Mol Microbiol. 2011; 82(4).
- Byrd MS, Pang B, Hong W, Waligora EA, Juneau RA, Armbruster CE, Weimer KE, Murrah K, Mann EE, Lu H, Sprinkle A, Parsek MR, Kock ND, Wozniak DJ, Swords WE. Direct evaluation of Pseudomonas aeruginosa biofilm mediators in a chronic infection model. Infect Immun. 2011; 79(8).
- Weimer KE, Juneau RA, Murrah KA, Pang B, Armbruster CE, Richardson SH, Swords WE. Divergent mechanisms for passive pneumococcal resistance to β-lactam antibiotics in the presence of Haemophilus influenzae. J Infect Dis. 2011; 203(4).
- Juneau RA, Pang B, Weimer KE, Armbruster CE, Swords WE. Nontypeable Haemophilus influenzae initiates formation of neutrophil extracellular traps. Infect Immun. 2011; 79(1).
- Weimer KE, Armbruster CE, Juneau RA, Hong W, Pang B, Swords WE. Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease. J Infect Dis. 2010; 202(7).
- Armbruster CE, Hong W, Pang B, Weimer KE, Juneau RA, Turner J, Swords WE. Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling. MBio. 2010; 1(3).
- Armbruster CE, Hong W, Pang B, Dew KE, Juneau RA, Byrd MS, Love CF, Kock ND, Swords WE. LuxS promotes biofilm maturation and persistence of nontypeable haemophilus influenzae in vivo via modulation of lipooligosaccharides on the bacterial surface. Infect Immun. 2009; 77(9).
Professional Memberships:
- Infectious Diseases Society of America (2016–present)
- American Society for Microbiology (2004–present)
Presentations:
- "Polymicrobial interactions modulate severity of catheter-associated urinary tract infection." Gordon Research Conference on Microbial Toxins and Pathogenesis (2018)
- "The interaction between pathogens in catheter-associated urinary tract infections in nursing homes" • ASM Microbe 2018 (2018)
- "Tn-Seq analysis of Providencia stuartii catheter-associated urinary tract infection (CAUTI) reveals newly identified virulence factors" ASM Microbe 2018 (2018)
- "Defining the role of Proteus mirabilis catalase activity during oxidative stress and biofilm formation" Witebsky Conference on Microbial Pathogenesis (2018)
- "Tn-Seq analysis of Providencia stuartii catheter-associated urinary tract infection (CAUTI) reveals newly identified virulence factors" Witebsky Conference on Microbial Pathogenesis (2018)
- "Relatedness of MRSA and VRE strains isolated from post-acute care patients and their environment: a longitudinal assessment" IDWeek, Infectious Diseases Society of America (2017)
- "Comparison of Methods for Estimating in vivo Growth Rate During Urinary Tract Infection" ASM Microbe 2017, American Society for Microbiology (2017)
- "Genome-Wide Transposon Mutagenesis of Proteus mirabilis: Essential Genes, Fitness Factors for Catheter-Associated Urinary Tract Infection, and the Impact of Polymicrobial Infection On Fitness Requirements" ASM Microbe 2017, American Society for Microbiology (2017)
- "Transposon Insertion Sequencing to Identify Providencia stuartii Essential Genes and Fitness Factors for Murine Catheter-Associated Urinary Tract Infection" ASM Microbe 2017, American Society for Microbiology (2017)
- "Burgeoning Short Stay Population: Impact on transmission of Multi-Drug Resistant Organisms (MDROs)" AGS 2017 Annual Meeting, American Geriatrics Society (2017)
- "Influence of Aging on Urinary Tract Infection Susceptibility and Severity" Claude D. Pepper Older Americans Independence Centers Annual Meeting, Claude D. Pepper Older Americans Independence Centers Annual Meeting (2017)
- "Multidrug-Resistant Organisms (MDRO) in Post-Acute Care: Dynamics From Admission Through Discharge" IDWeek, Infectious Diseases Society of America (2016)
- "Urease activity is enhanced during co-culture of common CAUTI pathogens and contributes to severity of disease in a murine infection model" IDWeek, Infectious Diseases Society of America (2016)
- "Urease Activity is Enhanced During Experimental Polymicrobial UTI And Promotes Tissue Damage and Bacteremia" Clinical and Scientific Advances in Urinary Tract Infections (2016)
- "Delineating the Role of Enhanced Urease Activity in Tissue Damage and Bacteremia During Polymicrobial Urinary Tract Infection" ASM Microbe 2016, American Society for Microbiology (2016)
- "Measuring Differential Growth Rates of Uropathogenic Escherichia coli Strains in vitro and During Experimental Murine Urinary Tract Infection" ASM Microbe 2016, American Society for Microbiology (2016)
- "Partners in Crime: Enhanced urease activity during co-culture of bacterial uropathogens" ASM Microbe 2016, American Society for Microbiology (2016)
- "Transposon Insertion Sequencing to Identify Proteus mirabilis Fitness Factors for Murine Catheter-Associated Urinary Tract Infection" ASM Microbe 2016, American Society for Microbiology (2016)
- "Klebsiella pneumoniae Catheter-Associated Urinary Tract Infections are Associated with Acute Changes in Mental Status" IDWeek, Infectious Diseases Society of America (2015)
- "Double Trouble: Coinfection with Proteus mirabilis and Providencia stuartii Enhances the Severity of Catheter-Associated Urinary Tract Infection" Molecular Pathogenesis: Mechanisms of Infectious Disease, Federation of American Societies for Experimental Biology (2015)
- "Contribution of Bacterial Urease to Enhanced Pathogenicity During Polymicrobial Urinary Tract Infection" ASM General Meeting, American Society for Microbiology (2015)
- "Synergistic urease activity in vitro and during experimental polymicrobial urinary tract infection" ASM General Meeting, American Society for Microbiology (2015)
- "Investigating Molecular Mechanisms of Enhanced Pathogenicity during Polymicrobial Urinary Tract Infection" 1st ASM Conference on Polymicrobial Infections, American Society for Microbiology (2014)
- "Polymicrobial Infections" 1st ASM Conference on Polymicrobial Infections, American Society for Microbiology (2014)
- "Synergistic urease activity during experimental polymicrobial urinary tract infection" 1st ASM Conference on Polymicrobial Infections, American Society for Microbiology (2014)
- "Synergistic urease activity and increased incidence of bacteremia and urolithiasis resulting from coinfection of the urinary tract" ASM General Meeting, American Society for Microbiology (2014)
- "Proteus mirabilis swarming occurs in response to factors present in urine and requires excess L-glutamine" Clinical and Scientific Advances in Urinary Tract Infections (2013)
- "Proteus mirabilis swarming occurs in response to factors present in urine and requires excess L-glutamine" ASM General Meeting, American Society for Microbiology (2013)
- "Proteus mirabilis swarming motility: influence of amino acids, polyamine synthesis, and metabolism" ASM General Meeting, American Society for Microbiology (2012)
- "Identification of factors that trigger Proteus mirabilis swarming motility" 18th Annual Midwest Microbial Pathogenesis Conference (2011)
Service Activities:
- Microbiology and Immunology Master's Program Curriculum Task Force; Three-member task force (with Tilman Baumstark and John Panepinto) to evaluate the current Master's program curriculum.; Member (2018–present)
- Peer Review; Infection, Disease & Health (Elsevier); Ad Hoc Reviewer (2017–present)
- Peer Review; Medical Microbiology and Immunology (Springer); Ad Hoc Reviewer (2017–present)
- Peer Review; Journal of Infection (Elsevier); Ad Hoc Reviewer (2016–present)
- Peer Review; Methods (Elsevier); Ad Hoc Reviewer (2016–present)
- Peer Review; Microbiology (Society for General Microbiology); Ad Hoc Reviewer (2015–present)
- Planning committee and primary organizer; Fall 2015 meeting of the Michigan branch of the American Society for Microbiology; Organizing Committee Member (2015)
- Peer Review; Clinical and Vaccine Immunology (American Society for Microbiology); Ad Hoc Reviewer (2015–present)
- President; University of Michigan Microbiology & Immunology Departmental Postdoctoral Association; President (2015)
- Peer Review; Infection and Immunity (ASM); Ad Hoc Reviewer (2014–present)
- Peer Review; Applied Environmental Microbiology (ASM); Ad Hoc Reviewer (2014–present)
- Peer Review; Antimicrobial Agents and Chemotherapy (ASM); Ad Hoc Reviewer (2014–present)
- Peer Review; Clinical Microbiology Reviews (ASM); Ad Hoc Reviewer (2013–present)
- Vice President; University of Michigan Microbiology & Immunology Departmental Postdoctoral Association; Vice President (2012)