The contribution of proteomics towards deciphering the enigma of Coxiella burnetii

Abstract

Coxiella burnetii, the causative agent of Q fever, is an intracellular bacterium and a potential weapon for bioterrorism. The widespread throughout the world, zoonosis is manifested clinically as a self-limited febrile illness, as pneumonia (acute Q fever) or as a chronic illness with endocarditis being its major complication. The recent Netherlands Q fever outbreak has driven the bacterium from a relatively cryptic, underappreciated, "niche" microorganism on the sideline of bacteriology, to one of possibly great impact on public health. Advances in the study of this microorganism proceeded slowly, primarily due to the, until recently, obligatory intracellular nature of the pathogen that in its virulent phase I must be manipulated under biosafety level-3 conditions. Proteomic studies, in particular, have generated a vast amount of information concerning several aspects of the bacterium such as virulence factors, detection/diagnostic and immunogenic biomarkers, inter-/intraspecies variation, resistance to antibiotics, and secreted effector proteins with significant clinical impact. The phenomenon observed following the genomics era, that of generation and accumulation of huge amount of data that ultimately end up unexploited on several databases, begins to emerge in the proteomics field as well. This review will focus on the advances in the field of C. burnetii proteomics through MS, attempting in parallel to utilize some of the proteomics findings by suggesting future directions for the improvement of Q fever diagnosis and therapy.

MALDI-TOF mass spectrometry: an emerging technology for microbial identification and diagnosis

“…Conventionally, organisms which pose severe threats as agents of bioterrorism have been identified by phenotypic, genotypic, and immunological identification systems which are slow, cumbersome and pose significant risk to the laboratory personnel. Recently various researchers reported MALDI-TOF MS as a simple, rapid and reliable approach to identify highly pathogenic organisms like Brucella spp., Coxiella burnetti , Bacillus anthracis, Francisella tularensis , and Y. pestis ( Shaw et al, 2004 ; Pierce et al, 2007 ; Lasch et al, 2009 ; Ayyadurai et al, 2010 ; Seibold et al, 2010 ; Lista et al, 2011 ; Vranakis et al, 2013 ).…”

Recent progress in glycomics and proteomics of the Q fever bacterium Coxiella burnetii

“…In summary, as many as 822 uniquely identified proteins which represent 45% of all ORFs of C. burnetii were identified in the proteomic studies mentioned here. Given the fact that no organism expresses its entire proteome potential at a given time, the identification of almost half of the bacterium΄s proteome can be considered as a success (Vranakis et al, 2013). So far, proteomic studies have generated a vast amount of infor- Workflow of protein identification using LC-MS/MS analysis mation on several aspects of the bacterium such as virulence factors, detection/diagnostic and immunogenic biomarkers, inter/intra-species variation, resistance to antibiotics, SAPs and secreted effector proteins with significant clinical impact.…”

“…Sixty of the proteins are cell envelope related and 52 proteins with post-translational modification, degradation, or protein turnover. Due to the resistant nature of the bacterium, other functional categories of particular interest comprise proteins involved in pathogenesis 17, toxin production and resistance (13), adaptation to atypical conditions (11), and detoxification (6) (Vranakis et al, 2013). Thus, the identified proteins provide an additional insight into the pathogenesis and immunity of Q fever.…”

Identification ofCoxiella burnetiisurface-exposed and cell envelope associated proteins using a combined bioinformatics plus proteomics strategy

“…The glycolytic enzymes, chaperones, elongation factor Tu (EF‐Tu), ribosomal proteins, membrane proteases, and cell division proteins are common among this group of proteins (Table ). Some of these proteins have been identified as effector proteins translocated by the Type IV secretion system . Glycolytic proteins with moonlighting activities have been found at the surface of many bacteria .…”

“…Understanding the surface proteome of C. burnetii is of special importance because it can reveal the complexity of biological processes taking place at the interface between the bacterium and the external milieu . These environment‐accessible, surface‐exposed and cell envelope associated proteins (SECEP), are not only involved in the uptake of nutrients and the release of waste, but they also support physical interactions of the bacteria with living surfaces and serve as sensors for extracellular signals .…”