Identification of potentially involved proteins in levofloxacin resistance mechanisms in Coxiella burnetii.
The etiological agent of Q fever, Coxiella burnetii, is an obligate intracellular bacterium that multiplies within a phagosome-like parasitophorous vacuole. Fluoroquinolones have been used as an alternative therapy for Q fever. Resistance to fluoroquinolones can arise via several mechanisms utilized by pathogens to avoid killing. Until today, genome-based studies have shown that the main mechanism of C. burnetii to resist inhibition by fluoroquinolones is based on mutations in quinolone-resistance-determining region (QRDR). In this study, in a broader search at the protein level for C. burnetii mechanisms that confer resistance to fluoroquinolones, the proteomes of in vitro developed fluoroquinolone resistant bacteria and susceptible bacteria were compared using the MS-driven combined fractional diagonal chromatography (COFRADIC) proteomics technique. Quantitative comparison of the 381 proteins identified in both strains indicated the different expression of 15 bacterial proteins. These proteins are involved in different cellular processes indicating that the antibiotic resistance mechanism of the bacterium is a multifaceted process.
Department of Clinical Bacteriology, Parasitology, Zoonoses and Geographical Medicine, Medical School, University of Crete, Heraklion, Greece.
Iosif
I
Vranakis
Pieter-Jan
PJ
De Bock
Anastasia
A
Papadioti
Yannis
Y
Tselentis
Kris
K
Gevaert
Georgios
G
Tsiotis
Anna
A
Psaroulaki
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000032:analysis / Q000378:metabolism*; D002522:Chlorocebus aethiops; D016997:Coxiella burnetii / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000502:physiology; D064704:Levofloxacin; D013058:Mass Spectrometry; D015242:Ofloxacin / Q000494:pharmacology*; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics; D015854:Up-Regulation / Q000187:drug effects; D014709:Vero Cells
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D020543:Proteome; D064704:Levofloxacin; D015242:Ofloxacin