Proteomic Investigation of the Signal Transduction Pathways Controlling Colistin Resistance in Klebsiella pneumoniae
| Autor: | Ching Hei Phoebe Cheung, Kate J. Heesom, Punyawee Dulyayangkul, Matthew B. Avison |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proteomics
Operon Klebsiella pneumoniae Mutant Microbial Sensitivity Tests medicine.disease_cause Microbiology 03 medical and health sciences Bacterial Proteins Mechanisms of Resistance Drug Resistance Bacterial Protein biosynthesis medicine Pharmacology (medical) 030304 developmental biology Pharmacology 0303 health sciences Mutation biology 030306 microbiology Chemistry Colistin biochemical phenomena metabolism and nutrition biology.organism_classification Anti-Bacterial Agents Infectious Diseases Regulon bacteria Signal transduction medicine.drug Signal Transduction |
| Zdroj: | Antimicrob Agents Chemother Phoebe Cheung, C H, Dulyayangkul, P, Heesom, K J & Avison, M B 2020, ' Proteomic Investigation of the Signal Transduction Pathways Controlling Colistin Resistance in Klebsiella pneumoniae ', Antimicrobial Agents and Chemotherapy . https://doi.org/10.1128/AAC.00790-20 |
| Popis: | Colistin resistance in Klebsiella pneumoniae is predominantly caused by mutations that increase expression of the arn (also known as pbg or pmrF) operon. Expression is activated by the PhoPQ and PmrAB two-component systems. Constitutive PhoPQ activation occurs directly by mutation or following loss of MgrB. PhoPQ may also cross-activate PmrAB via the linker protein PmrD. Using proteomics, we show that MgrB loss causes a wider proteomic effect than direct PhoPQ activation, suggesting additional targets for MgrB. Different mgrB mutations cause different amounts of Arn protein production, which correlated with colistin MIC. Disruption of phoP in an mgrB mutant had a reciprocal effect to direct activation of PhoQ in a wild-type background, but the regulated proteins showed almost total overlap. Disruption of pmrD or pmrA slightly reduced Arn protein production in an mgrB mutant, but production was still high enough to confer colistin resistance; disruption of phoP conferred wild-type Arn production and colistin MIC. Activation of PhoPQ directly, or through mgrB mutation did not significantly activate PmrAB or PmrC production but direct activation of PmrAB by mutation did, and also activated Arn production and conferred colistin resistance. There was little overlap between the PmrAB and PhoPQ regulons. We conclude that under the conditions used for colistin susceptibility testing, PhoPQ-PmrD-PmrAB cross-regulation is not significant and that independent activation of PhoPQ or PmrAB is the main reason that Arn protein production increases above the threshold required for colistin resistance. |
| Databáze: | OpenAIRE |
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