|Academic Profile |
| || |
Asst Prof Kimberly Kline
Nanyang Assistant Professor (NRF)
School of Biological Sciences
College of Science
- PhD Northwestern University 2005
- MPH Northwestern University 2004
- BA Saint Olaf College 1996
|Kimberly Kline received her MPH and PhD from Northwestern University in Chicago, where she studied molecular mechanisms involved in pilus antigenic variation in Neisseria gonorrhoeae, the causative agent of gonorrhea. As a postdoctoral fellow at Washington University in St. Louis and at the Karolinska Institute in Stockholm, she developed novel mono- and poly-microbial urinary tract infection models to study the contribution of Gram positive bacterial surface structures to disease progression. Her lab investigates mechanisms by which Gram positive bacteria, such as Enterococcus faecalis, spatially and temporally organize surface structure assembly sites at a subcellular level. Her lab integrates these studies of fundamental cellular processes with in vivo infection models to study the contribution of localized surface structure biogenesis to disease progression.|
|Enterococci are one of the leading causes of hospital-acquired infections and cause a variety of disease states including endocarditis, bacteremia, meningitis, wound infections, and urinary tract infections. The ability to form biofilms in vivo and in the environment is critical for many enterococcus infections. Enterococcal and other Gram positive infections are increasingly problematic due to the rising prevalence of antibiotic resistance. Vancomycin-resistant enterococci (VRE) are of particular concern in hospital settings. Enterococcus faecalis can also share antibiotic resistance genes with methicillin-resistant Staphylococcus aureus (MRSA) resulting in bacterial infections that are exceptionally difficult to treat. Therefore, discovering new strategies to combat infections caused by these organisms is of utmost importance.|
E. faecalis must interact with other bacteria to transfer genetic material and with host cells to cause disease, and utilize extracellular proteins and polymers (pili) to mediate these processes. Thus, understanding protein secretion and the pathways that assemble and attach the extracellular proteins to the cell surface promotes our understanding of pathogenesis. We previously demonstrated that several E. faecalis surface proteins are secreted, polymerized, and anchored to the cell wall at distinct focal sites on the bacterial surface. Using a combination of genetics, genomics, biochemistry, and imaging, we are exploring the molecular mechanisms that dictate site selection, organization, and maintenance of localized virulence factor assembly sites in bacteria. We integrate studies of basic cellular processes with in vivo infection models to assess the contribution of localized surface structure biogenesis to disease progression. We have developed several urinary tract infection models to study the pathogenesis of Gram positive organisms. These and other models enable the study of in vivo biofilm formation, infection dynamics, and the host response.
Collectively, we assess the functional consequence of perturbing focal localization of virulence factor assembly at the single cell level, the bacterial population level, and in models of disease. The overarching goal of these studies is to understand new aspects of fundamental biological processes and to identify novel anti-infective and therapeutic targets.
- Academic Research Fund Tier 3 (2014-) [by Ministry of Education (MOE)]
- National Medical Research Council (2015-2018) [by National Medical Research Council (NMRC)]
- Singapore Centre on Environmental Life Sciences Engineering (SCELSE) (2016-) [by National Institutes of Health]
- Localized Virulence Factor Assembly in Gram Positive Bacteria: Mechanism of Coordination and Therapeutic Targeting
- Mechanisms of Enterococcal Niche Modulation during Polymicrobial Infection
- Novel antimicrobial hydrogel formulations for biomedical devices
- Selective Contact-Active Cationic Antimicrobial Biomacromolecules
- Selective contact-active antimicrobial bio-macromolecules
- Rashid R, Cazenave-Gassiot A, Gao IH, Nair ZJ, Kumar JK, Gao L, Kline KA, Wenk MR. (2017). Comprehensive analysis of phospholipids and glycolipids in the opportunistic pathogen Enterococcus faecalis. PLoS ONE, .
- Goh HM, Yong MH, Chong KK, Kline KA. (2017). Model systems for the study of Enterococcal colonization and infection. Virulence, .
- Damien Keogh, Wei Hong Tay, Yao Yong Ho, Jennifer L. Dale, Siyi Chen, Shivshankar Umashankar, Rohan B. H. Williams, Swaine L. Chen, Gary M. Dunny and Kimberly A. Kline. (2016). Enterococcal Metabolite Cues Facilitate Interspecies Niche Modulation and Polymicrobial Infection. Cell Host and Microbe, (20), 493-503.
- *Rousseau M, *Goh HM, Holec S, Albert ML, Williams RB, ^Ingersoll MA, ^Kline KA. (2016). Bladder catheterization increases susceptibility to infection that can be prevented by prophylactic antibiotic treatment. JCI insight, 1(15), e88178.
- Mitra SD, Afonina I, Kline KA. (2016). Right Place, Right Time: Focalization of Membrane Proteins in Gram-Positive Bacteria. Trends in Microbiology, .