Role of the Two Component Signal Transduction System CpxAR in Conferring Cefepime and Chloramphenicol Resistance in Klebsiella pneumoniae NTUH-K2044

Autor: Govindan Rajamohan, Vasanth Vaidyanathan, Vijaya Bharathi Srinivasan, Amitabha Mondal
Rok vydání: 2012
Předmět:
Bacterial Diseases
Nosocomial Infections
Klebsiella pneumoniae
Antibiotics
lcsh:Medicine
Electrophoretic Mobility Shift Assay
Chloramphenicol Resistance
Molecular Cell Biology
lcsh:Science
Cefepime
Genetics
Multidisciplinary
Protein Kinase Signaling Cascade
biology
Reverse Transcriptase Polymerase Chain Reaction
Klebsiella Pneumonia
Enterobacteriaceae
Signaling Cascades
Anti-Bacterial Agents
RNA
Bacterial
Infectious Diseases
Medicine
Signal transduction
Research Article
Signal Transduction
Bacterial Outer Membrane Proteins
medicine.drug
DNA
Bacterial
medicine.drug_class
Blotting
Western
Molecular Sequence Data
Microbial Sensitivity Tests
Real-Time Polymerase Chain Reaction
beta-Lactam Resistance
Bacterial genetics
Microbiology
Bacterial Proteins
Osmotic Pressure
Operon
medicine
Amino Acid Sequence
RNA
Messenger
Biology
Base Sequence
Sequence Homology
Amino Acid
lcsh:R
Computational Biology
Molecular Development
biology.organism_classification
Signaling
Klebsiella Infections
Cephalosporins
Multiple drug resistance
Oxidative Stress
Chloramphenicol
lcsh:Q
Protein Kinases
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 4, p e33777 (2012)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0033777
Popis: BACKGROUND: Klebsiella pneumoniae is a gram-negative, non-motile, facultative anaerobe belonging to the Enterobacteriaceae family of the γ-Proteobacteria class in the phylum Proteobacteria. Multidrug resistant K. pneumoniae have caused major therapeutic problems worldwide due to emergence of extended-spectrum β-lactamase producing strains. Two-component systems serve as a basic stimulus-response coupling mechanism to allow organisms to sense and respond to changes in many different environmental conditions including antibiotic stress. PRINCIPAL FINDINGS: In the present study, we investigated the role of an uncharacterized cpxAR operon in bacterial physiology and antimicrobial resistance by generating isogenic mutant (ΔcpxAR) deficient in the CpxA/CpxR component derived from the hyper mucoidal K1 strain K. pneumoniae NTUH-K2044. The behaviour of ΔcpxAR was determined under hostile conditions, reproducing stresses encountered in the gastrointestinal environment and deletion resulted in higher sensitivity to bile, osmotic and acid stresses. The ΔcpxAR was more susceptible to β-lactams and chloramphenicol than the wild-type strain, and complementation restored the altered phenotypes. The relative change in expression of acrB, acrD, eefB efflux genes were decreased in cpxAR mutant as evidenced by qRT-PCR. Comparison of outer membrane protein profiles indicated a conspicuous difference in the knock out background. Gel shift assays demonstrated direct binding of CpxR(KP) to promoter region of ompC(KP) in a concentration dependent manner. CONCLUSIONS AND SIGNIFICANCE: The Cpx envelope stress response system is known to be activated by alterations in pH, membrane composition and misfolded proteins, and this systematic investigation reveals its direct involvement in conferring antimicrobial resistance against clinically significant antibiotics for the very first time. Overall results displayed in this report reflect the pleiotropic role of the CpxAR signaling system and diversity of the antibiotic resistome in hyper virulent K1 serotype K. pneumoniae NTUH-K2044.
Databáze: OpenAIRE
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