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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 ?-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, whereas 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.

SUBMITTER: Keasey SL 

PROVIDER: S-EPMC6442359 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Decreased Antibiotic Susceptibility Driven by Global Remodeling of the <i>Klebsiella pneumoniae</i> Proteome.

Keasey Sarah L SL   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 <i>Klebsiella pneumoniae</i> that was isolated from a lethal outbreak within laboratory colonies of <i>Chlorocebus aethiops sabaeus</i> monkeys. Bacterial responses to the ribosomal synthesis inhibitors streptomycin and doxycycline re  ...[more]

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