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Mol Cell Proteomics. 2019 Jan 7. pii: mcp.RA118.000739. doi: 10.1074/mcp.RA118.000739. [Epub ahead of print]

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

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USAMRIID, United States of America.
Frederick National Laboratory for Cancer Research.
Frederick National Laboratory for Cancer Research, United States.
USAMRMC, United States of America.
United States Army Medical Research Institute of Infectious Diseases, United States of America


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.


Bacteria; Drug resistance; Mass Spectrometry; Pathogens; Systems biology*

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