BACKGROUND: While the importance of fluid dynamical conditions is well recognized in the growth of biofilms, their role during bacteremia is unknown. We examined the impact of physiological fluid shear forces on the development of multicellular aggregates of Klebsiella pneumoniae. METHODS: Wild-type and O-antigen or capsular mutants of K. pneumoniae were grown as broth culture in a Taylor-Couette flow cell configured to provide continuous shear forces comparable to those encountered in the human arterial circulation (ie, on the order of 1.0 Pa). The size distribution and antibiotic resistance of aggregates formed in this apparatus were determined, as was their ability to persist in the bloodstream of mice following intravenous injection. RESULTS: Unlike growth in shaking flasks, bacteria grown in the test apparatus readily formed aggregates, a phenotype largely absent in capsular mutants and to a lesser degree in O-antigen mutants. Aggregates were found to persist in the bloodstream of mice. Importantly, organisms grown under physiological shear were found to have an antibiotic resistance phenotype intermediate between that of fully planktonic and biofilm states. CONCLUSIONS: When grown under intravascular-magnitude fluid dynamic conditions, K. pneumoniae spontaneously develops into multicellular aggregates that are capable of persisting in the circulation and exhibit increased antibiotic resistance.
BACKGROUND: While the importance of fluid dynamical conditions is well recognized in the growth of biofilms, their role during bacteremia is unknown. We examined the impact of physiological fluid shear forces on the development of multicellular aggregates of Klebsiella pneumoniae. METHODS: Wild-type and O-antigen or capsular mutants of K. pneumoniae were grown as broth culture in a Taylor-Couette flow cell configured to provide continuous shear forces comparable to those encountered in the human arterial circulation (ie, on the order of 1.0 Pa). The size distribution and antibiotic resistance of aggregates formed in this apparatus were determined, as was their ability to persist in the bloodstream of mice following intravenous injection. RESULTS: Unlike growth in shaking flasks, bacteria grown in the test apparatus readily formed aggregates, a phenotype largely absent in capsular mutants and to a lesser degree in O-antigen mutants. Aggregates were found to persist in the bloodstream of mice. Importantly, organisms grown under physiological shear were found to have an antibiotic resistance phenotype intermediate between that of fully planktonic and biofilm states. CONCLUSIONS: When grown under intravascular-magnitude fluid dynamic conditions, K. pneumoniae spontaneously develops into multicellular aggregates that are capable of persisting in the circulation and exhibit increased antibiotic resistance.
Authors: Stephen P Dzul; Margaret M Thornton; Danial N Hohne; Elizabeth J Stewart; Aayush A Shah; David M Bortz; Michael J Solomon; John G Younger Journal: Appl Environ Microbiol Date: 2011-01-14 Impact factor: 4.792
Authors: Michael C Kreissl; Hsiao-Ming Wu; David B Stout; Waldemar Ladno; Thomas H Schindler; Xiaoli Zhang; John O Prior; Mayumi L Prins; Arion F Chatziioannou; Sung-Cheng Huang; Heinrich R Schelbert Journal: J Nucl Med Date: 2006-06 Impact factor: 10.057
Authors: Christina M Nypaver; Margaret M Thornton; Suellen M Yin; David O Bracho; Patrick W Nelson; Alan E Jones; David M Bortz; John G Younger Journal: Am J Respir Cell Mol Biol Date: 2009-12-11 Impact factor: 6.914
Authors: Peter B Lockhart; Michael T Brennan; Howell C Sasser; Philip C Fox; Bruce J Paster; Farah K Bahrani-Mougeot Journal: Circulation Date: 2008-06-09 Impact factor: 29.690
Authors: Travis J Wiles; J Paul Norton; Sara N Smith; Adam J Lewis; Harry L T Mobley; Sherwood R Casjens; Matthew A Mulvey Journal: PLoS Pathog Date: 2013-02-14 Impact factor: 6.823