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Colistin resistance in Escherichia coli

ABSTRACT: Colistin resistance in human faecal Escherichia coli as the result of two distinct evolutionary pathways in France

PROVIDER: PRJEB28020 | ENA |

REPOSITORIES: ENA

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Proteomic changes of Klebsiella pneumoniae in response to colistin treatment and crrB mutation-mediated colistin resistance

Project description:Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.

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Aminocandin versus Aminocandin plus Colistin

Project description:We found that the antibiotic colistin acts synergistically with antifungals of the echinocandin class (e.g. aminocandin) on C. albicans cells. In order to elucidate the mode of action of colistin in fungi we performed microarray analysis of samples treated with only aminocandin (0.00125µg/ml) or treated with aminocandin (0.00125µg/ml) and colistin (5µg/ml). We compared: (A). untreated cells to cells treated with aminocandin only; (B). cells treated with aminocandin to cells treated with aminocandin and colistin (which is the focus of this experiment). By comparing those datasets it should be possible to identify genes differentially expressed in response to aminocandin and in response to both drugs. And subsequently to be able to interpret where in the cell colistin acts. (See related experiment in ArrayExpress: E-MEXP-3437 for comparison between untreated cells vs cells treated with aminocandin only.)

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