Proteomics

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Decreased antibiotic susceptibility driven by global remodeling of the Klebsiella pneumoniae proteome


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.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Klebsiella pneumoniae  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Not Available

SUBMITTER: Moo-Jin Suh  

LAB HEAD: Suh, Moo-Jin

PROVIDER: PXD010244 | Pride | 2019-03-14

REPOSITORIES: Pride

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Publications

Decreased Antibiotic Susceptibility Driven by Global Remodeling of the Klebsiella pneumoniae Proteome.

Keasey Sarah L SL   Suh Moo-Jin MJ   Suh Moo-Jin MJ   Das Sudipto S   Blancett Candace D CD   Zeng Xiankun X   Andresson Thorkell T   Sun Mei G MG   Ulrich Robert G RG  

Molecular & cellular proteomics : MCP 20190107 4


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 dist  ...[more]

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