MvfR Controls Tolerance to Polymyxin B by Regulating rfaD in Pseudomonas aeruginosa

Abstract

Antibiotic resistance imposes a considerable challenge for the treatment of P. aeruginosa infections. Polymyxins are the last-resort antibiotics for the treatment of multidrug-resistant P. aeruginosa infections.

Widespread fungal–bacterial competition for magnesium lowers bacterial susceptibility to polymyxin antibiotics

“…Hypermutation is a hallmark of antibiotic-resistance acquisition that has been observed in several previous experimental evolution studies [ 56 ]. As a result of hypermutation, each monoculture population acquired hundreds of fixed mutations ( Fig 4D ), including mutations previously shown to confer colistin resistance, in genes such as pmrB [ 57 ], ptsP [ 58 , 59 ], pqsR [ 58 ], colS [ 60 , 61 ], porins [ 58 ], and proteins related to bacterial motility [ 62 ] ( Fig 4E and S3 Table ). In contrast, none of the co-culture-evolved populations became hypermutators; each only harbored 6 to 8 fixed mutations ( Fig 4D ), primarily in other targets for colistin resistance, such as genes in LPS biosynthesis [ 63 ] and an outer-membrane protein oprH [ 52 ] (Figs 4E and S18 and S3 Table ).…”

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“…Hypermutation is a hallmark of antibiotic-resistance acquisition that has been observed in several previous experimental evolution studies [56]. As a result of hypermutation, each monoculture population acquired hundreds of fixed mutations (Fig 4D ), including mutations previously shown to confer colistin resistance, in genes such as pmrB [57], ptsP [58,59], pqsR [58], colS [60,61], porins [58], and proteins related to bacterial motility [62] (Fig 4E and S3 Table ). In contrast, none of the co-culture-evolved populations became hypermutators; each only harbored 6 to 8 fixed mutations (Fig 4D ), primarily in other targets for colistin resistance, such as genes in LPS biosynthesis [63] and an outer-membrane protein oprH [52] (Figs 4E and S18 and S3 Table ).…”

Untitled

“…Hypermutation is a hallmark of antibiotic-resistance acquisition that has been observed in several previous experimental evolution studies [56]. As a result of hypermutation, each monoculture population acquired hundreds of fixed mutations (Fig 4D ), including mutations previously shown to confer colistin resistance, in genes such as pmrB [57], ptsP [58,59], pqsR [58], colS [60,61], porins [58], and proteins related to bacterial motility [62] (Fig 4E and S3 Table ). In contrast, none of the co-culture-evolved populations became hypermutators; each only harbored 6 to 8 fixed mutations (Fig 4D ), primarily in other targets for colistin resistance, such as genes in LPS biosynthesis [63] and an outer-membrane protein oprH [52] (Figs 4E and S18 and S3 Table ).…”