摘要

The prevalence of infections caused by multidrug-resistant gram-negative Acinetobacter baumannii strains and the lack of novel antibiotics under development are posing a global dilemma, forcing a resurgence of the last-line antibiotic colistin. Our aim was to use atomic force microscopy (AFM) to investigate the morphology and topography of paired colistin-susceptible and -resistant cells from colistin-heteroresistant A. baumannii strains as a function of bacterial growth phase and colistin exposure. An optimal AFM bacterial sample preparation protocol was established and applied to examine three paired strains. Images revealed rod-shaped colistin-susceptible cells (1.65 /- 0.27 mu m by 0.98 /- 0.07 mu m) at mid-logarithmic phase, in contrast to spherical colistin-resistant cells (1.03 /- 0.09 mu m); the latter were also more diverse in appearance and exhibited a rougher surface topography (7.05 /- 1.3 nm versus 11.4 /- 2.5 nm for susceptible versus resistant, respectively). Cellular elongation up to similar to 18 mu m at stationary phase was more commonly observed in susceptible strains, although these "worm-like" cells were also observed occasionally in the resistant population. The effects of colistin exposure on the cell surface of colistin-susceptible and -resistant cells were found to be similar; topographical changes were minor in response to 0.5 mu g/ml colistin; however, at 4 mu g/ml colistin, a significant degree of surface disruption was detected. At 32 mu g/ml colistin, cellular clumping and surface smoothening were evident. Our study has demonstrated for the first time substantial morphological and topographical differences between colistin-susceptible and -resistant cells from heteroresistant A. baumannii strains. These results contribute to an understanding of colistin action and resistance in regard to this problematic pathogen.

  • 出版日期2009-12
  • 单位CSIRO