Multiple drug resistant Acinetobacter baumannii chloramphenicol resistance requires an inner membrane permease [PublishAheadOfPrint]

Acinetobacter baumannii is a Gram negative organism that is a cause of hospital acquired multidrug resistant (MDR) infections. A. baumannii has a unique cell surface compared to many other Gram-negative pathogens in that it can live without LPS and it has a high content of cardiolipin in the outer membrane. Therefore, to better understand the cell envelope and mechanisms of A. baumannii MDR, we screened a transposon library for mutants with defective permeability barrier function, as defined as a deficiency in the ability to exclude the phosphatase chromogenic substrate, 5-Bromo-4-chloro-3-indolyl phosphate (XP). We identified multiple mutants in the gene ABUW_0982, predicted to encode a permease broadly present in A. baumannii isolates, with increased susceptibility to the ribosome targeting antibiotic chloramphenicol (CHL). Moreover, when compared to other known CHL resistance genes such as chloramphenicol acyl-transferases, we find ABUW_0982 is the primary determinant of intrinsic CHL resistance in A. baumannii strain 5075, an important isolate responsible for severe MDR infections in humans. Finally, studies measuring the efflux of chloramphenicol and expression of ABUW_0982 in CHL-susceptible E. coli support the conclusion that ABUW_0982 encodes a single-component efflux protein with specificity for small, hydrophobic molecules, including CHL.

https://ift.tt/2JwMFyU