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"Researchers have used an imaging technique which relies on touch instead of light to show how a last-line antibiotic causes the outer armour of bacteria to bubble, distort and shed away.
The findings could help make polymycins – a last resort treatment for infections caused by gram-negative bacteria – more effective.
“Polymyxins are an important line of defence against Gram-negative bacteria, which cause many deadly drug-resistant infections. It is important we understand how they work,” ...
“Through capturing these incredible images of single cells, we’ve been able to show that this class of antibiotics only work with help from the bacterium, and if the cells go into a hibernation-like state, the drugs no longer work – which is very surprising.” ...
They found the antibiotic caused gram-negative bacterial cells to produce more of their outer membrane and then shed it. This left gaps in their defences allowing antibiotic to enter and kill them.
However, this did not happen when the cells were in a dormant state. ...
Polymyxin B was able to kill the dormant cells but only 15 minutes after they were provided with a food source – sugar. ..."
From the abstract:
"Polymyxin antibiotics target lipopolysaccharides (LPSs) in both membranes of the bacterial cell envelope, leading to bacterial killing through a poorly defined mechanism.
Here we demonstrate that metabolic activity [of the bacteria] is essential for the lethality of clinically relevant doses of polymyxin B (PmB) and leverage this insight to determine its mode of action.
PmB killed exponential-phase Escherichia coli but did not eliminate stationary-phase cells unless a carbon source was available.
Antibiotic lethality correlated with surface protrusions visible by atomic force microscopy and LPS loss from the outer membrane via processes that required LPS synthesis and transport but that were blocked by the MCR-1 polymyxin resistance determinant.
While energy-dependent outer-membrane disruption was not directly lethal, it facilitated PmB access to the inner membrane, which the antibiotic permeabilized in an energy-independent manner, leading to cell death.
This work reveals how metabolic inactivity confers tolerance of an important, membrane-targeting antibiotic."
Fig. 1: PmB lethality requires metabolic activity and is associated with significant morphological changes to the cell surface.
Composite image of Escherichia coli exposed to the polymyxin antibiotic. The images show the changes to the outer layer of armour over time. From left to right: untreated bacterium; bacterium after 15 minutes; after 30 minutes; after 60 minutes; after 90 minutes. The white scale bar is 250 nanometres across.
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