Decreased antibiotic susceptibility driven by global remodeling of the Klebsiella pneumoniae proteome
Collections
Author/Creator ORCID
Date
Type of Work
Department
Program
Citation of Original Publication
Sarah L Keasey, Moo-Jin Suh, Sudipto Das, Candace D Blancett, Xiankun Zeng, Thorkell Andresson, Mei G Sun and Robert G. Ulrich , Decreased antibiotic susceptibility driven by global remodeling of the Klebsiella pneumoniae proteome, Molecular & Cellular Proteomics January 7, 2019,https://doi.org/10.1074/mcp.RA118.000739
Rights
This work was written as part of one of the author's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.
This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
Public Domain Mark 1.0
This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
Public Domain Mark 1.0
Abstract
Bacteria can circumvent the effect of antibiotics by transitioning to a poorly understood physiological state that does not involve conventional genetic elements of resistance. Here we examine antibiotic susceptibility with a Class A β-lactamase+ invasive strain of Klebsiella pneumoniae that was isolated from a lethal outbreak within laboratory colonies of Chlorocebus aethiops sabaeus monkeys. Bacterial responses to the ribosomal synthesis inhibitors streptomycin and doxycycline resulted in distinct proteomic adjustments that facilitated decreased susceptibility to each antibiotic. Drug-specific changes to proteomes included proteins for receptor-mediated membrane transport and sugar utilization, central metabolism, and capsule production, while mechanisms common to both antibiotics included elevated scavenging of reactive oxygen species and turnover of misfolded proteins. Resistance to combined antibiotics presented integrated adjustments to protein levels as well as unique drug-specific proteomic features. Our results demonstrate that dampening of Klebsiella pneumoniae susceptibility involves global remodeling of the bacterial proteome to counter the effects of antibiotics and stabilize growth.