# Membrane Proteins ClcB, PtsI, and YcaM Mediate the Bactericidal Effects of Colistin in Escherichia coli

## TL;DR

This study identifies three membrane proteins in E. coli that play a role in the bactericidal effects of the antibiotic colistin.

## Contribution

The first evidence that ClcB, PtsI, and YcaM are involved in the cytotoxic pathway of polymyxin action in Gram-negative bacteria.

## Key findings

- Knockout of ClcB, PtsI, and YcaM affects E. coli susceptibility to colistin.
- The proteins are part of the cytotoxic pathway following polymyxin membrane intercalation.
- Findings were validated using growth assays, cytotoxic tests, and in vivo models.

## Abstract

Bacteria can be killed
very effectively by targeting their first
line of protection. The cell membranes (outer and inner membranes)
of Gram-negative bacteria are directly targeted by antibiotics, such
as polymyxins, via electrostatic interactions with their lipopolysaccharide
(LPS) fraction. The downstream effectspreceding the cell deathof
the disruptions of the bacterial membranes upon the intercalation
of these antibiotics are unknown. By screening a set of E. coli membrane protein knockouts, the absence of
three membrane transporters was shown to influence the susceptibility
to colistin. Their involvement was corroborated with growth assays
on gain-of-function strains, cytotoxic assays, and in vivo infections in an invertebrate animal model. This is the first-time
evidence that the disruption caused to membrane proteins, such as
the chloride channel ClcB, the sugar transport system component PtsI
and the hypothetical glutamate:GABA antiporter YcaM, is part of the
cytotoxic pathway that follows or is concomitant to the electrostatic
intercalations of polymyxins with the Gram-negative bacterial membrane.