Bose Lab


Staphylococcus aureus is a gram-positive bacteria found commonly in the nares of humans. However, it is also a prolific pathogen that can cause an array of infections, ranging from mild skin and soft tissue infections to severe diseases such as toxic shock syndrome, scalded skin syndrome, necrotizing pneumonia, necrotizing fasciitis, abscesses, and endocarditis. While once considered an opportunistic pathogen, the recent emergence of particular CA-MRSA strains that can infect otherwise healthy individuals has challenged this notion. In a very simplistic view, S. aureus infections can be grouped in two categories: 1) acute invasive disease dependent on the production of secreted factors such as toxins, and 2) chronic infections associated with biofilm formation which may or may not form on implanted medical devices. The research of my lab focuses on dissecting the molecular mechanisms behind the ability of this bacterium to cause disease. Specifically, we have two projects summarized below.

AtlA murein hydrolase: This project continues studies of the Atl murein hydrolase (enzyme which cleaves peptidoglycan). Atl is the major murein hydrolase of Staphylococci and is an important enzyme in maintaining proper peptidoglycan structure and daughter cell separation. In addition, we and others have shown that this bifunctional enzyme is required for biofilm formation. Our current studies are focused on how this enzyme is regulated, how mutations in AtlA alter cell physiology, and how AtlA contributes to biofilm formation.

VfrAB in virulence factor regulation:We identified the vfrAB operon during a transposon screen for mutants defective in production of the major virulence factor α-hemolysin. Previously a hypothetical protein of unknown function found in all gram-positive bacteria, we determined that VfrB controls the production of numerous virulence factors including α-hemolysin and proteases. Interestingly, the ΔvfrB mutant shows increased pathogenesis in a dermonecrosis model of infection. Further studies revealed that VfrB is a fatty acid kinase that is required for the uptake of exogenous fatty acids. VfrB (also called FakA) works with two partners FakB1 and FakB2. We are currently dissecting the role of VfrB in virulence factor regulation, cellular metabolism, and virulence.

New tools for the research community: While a lot of recent successes have enhanced our ability to genetically manipulate Staphylococcus to make mutants or track gene/protein expression, more tools are necessary. To accomplish our studies, we are heavily invested in the development of new genetic tools for studying S. aureus and closely related bacteria.

Select related publications:

  1. Krute, C.N., K.C Rice and J.L. Bose. 2017. VfrB is a key activator of the Staphylococcus aureus SaeRS two-component system. Journal of Bacteriology. PMID 28031278
  2. Krute, C.N., K.L. Krausz, M.A. Markiewicz, J.A. Joyner, S. Pokhrel, P.R. Hall, and J.L. Bose. 2016. Generation of a stable plasmid for in vitro and in vivo studies of Staphylococcus species. Applied and Environmental Microbiology. PMID: 27637878
  3. Krausz, K.L., and J.L Bose. 2014. Rapid Isolation of DNA from Staphylococcus. In J.L. Bose (ed), Genetic Manipulation of Staphylococci: Methods and Protocols. Springer Science + Business Media, LLC, New York, NY
  4. Krausz, K.L., and J.L Bose. 2014. Bacteriophage transduction in Staphylococcus aureus: broth-based method.  In J.L. Bose (ed), Genetic Manipulation of Staphylococci: Methods and Protocols. Springer Science + Business Media, LLC, New York, NY
  5. Bose, J.L. 2014. Chemical and UV Mutagenesis.  In J.L. Bose (ed), Genetic Manipulation of Staphylococci: Methods and Protocols. Springer Science + Business Media, LLC, New York, NY
  6. Moormieir, D., J.L. Bose, A.R. Horwsill, and K.W. Bayles. 2014. Temporal and stochastic control of Staphylococcus aureus biofilm development. mBio 5:e01341-14
  7. Parsons, J.B., T.C. Broussard, J.L. Bose, J.W. Rosch, P. Jackson, C. Subramanian, and C.O. Rock. 2014. Identification of a two-component fatty acid kinase responsible for host fatty acid incorporation by Staphylococcus aureus. PNAS 111:10532-10537
  8. Bose, J.L., S.M. Daly, P.R. Hall, and K.W. Bayles. 2014. Identification of the vfrAB operon in Staphylococcus aureus: a novel virulence factor regulatory locus. Infect. Immun. 5(82):1813-1822. doi: 10.1128/IAI.01655-13
  9. Bose, J.L. 2014. Genetic manipulation of Staphylococci. In P.D. Fey (ed.), Staphylococcus epidermidis: Methods and Protocols. Springer Science + Business Media, LLC, New York, NY
  10. Gries, C.M., J.L. Bose, A.S. Nuxoll, P.D, Fey, and K.W. Bayles. 2013. The Ktr potassium transport system in Staphylococcus aureus and its role in cell physiology, antimicrobial resistance, and pathogenesis. Mol. Microbiol. 89:760-773.
  11. Bose, J.L., P.D. Fey, and K.W. Bayles. 2013. Genetic tools to enhance the study of gene function and regulation in Staphylococcus aureus. Appl. Environ. Microbiol. 79:2218-2224.
  12. Fey, P.D., J.L. Endres, V.K. Yajjala, T.J. Widhelm, R.J. Boissy, J.L. Bose, and K.W. Bayles. 2013. A Genetic Resource for rapid and comprehensive screening of nonessential Staphylococcus aureus genes. mBio. 4(1):doi:10.1128/mBio.00537-12.
  13. Bose, J.L., M.K. Lehman, P.D Fey, and K.W. Bayles. 2012. Contribution of the Staphylococcus aureus AtlA AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation. PloS ONE 7:e42244.
  14. Kaplan, J.B., E.A. Izano, P. Gopal, M.T. Karwacki, S. Kim, J.L. Bose, K.W. Bayles, and A.R. Horswill. 2012. Low-levels of β-lactam antibiotics induce extracellular DNA release and biofilm formation in Staphylococcus aureus. mBio 3:e00198-12.