Intruders below the Radar: Molecular Pathogenesis of Bartonella spp.
01 Jan 2012-Clinical Microbiology Reviews (American Society for Microbiology)-Vol. 25, Iss: 1, pp 42-78
TL;DR: Current knowledge on the molecular processes underlying both the infection strategy and pathogenesis of Bartonella are compiled and their connection to the clinical presentation of human patients is discussed, which ranges from minor complaints to life-threatening disease.
Abstract: Bartonella spp. are facultative intracellular pathogens that employ a unique stealth infection strategy comprising immune evasion and modulation, intimate interaction with nucleated cells, and intraerythrocytic persistence. Infections with Bartonella are ubiquitous among mammals, and many species can infect humans either as their natural host or incidentally as zoonotic pathogens. Upon inoculation into a naive host, the bartonellae first colonize a primary niche that is widely accepted to involve the manipulation of nucleated host cells, e.g., in the microvasculature. Consistently, in vitro research showed that Bartonella harbors an ample arsenal of virulence factors to modulate the response of such cells, gain entrance, and establish an intracellular niche. Subsequently, the bacteria are seeded into the bloodstream where they invade erythrocytes and give rise to a typically asymptomatic intraerythrocytic bacteremia. While this course of infection is characteristic for natural hosts, zoonotic infections or the infection of immunocompromised patients may alter the path of Bartonella and result in considerable morbidity. In this review we compile current knowledge on the molecular processes underlying both the infection strategy and pathogenesis of Bartonella and discuss their connection to the clinical presentation of human patients, which ranges from minor complaints to life-threatening disease.
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TL;DR: It is proposed that biofilm formation is a critical step in the formation of vegetative masses during Bartonella-mediated endocarditis and represents a potential reservoir for persistence by these bacteria.
Abstract: Since the reclassification of the genus Bartonella in 1993, the number of species has grown from 1 to 45 currently designated members. Likewise, the association of different Bartonella species with human disease continues to grow, as does the range of clinical presentations associated with these bacteria. Among these, blood-culture-negative endocarditis stands out as a common, often undiagnosed, clinical presentation of infection with several different Bartonella species. The limitations of laboratory tests resulting in this underdiagnosis of Bartonella endocarditis are discussed. The varied clinical picture of Bartonella infection and a review of clinical aspects of endocarditis caused by Bartonella are presented. We also summarize the current knowledge of the molecular basis of Bartonella pathogenesis, focusing on surface adhesins in the two Bartonella species that most commonly cause endocarditis, B. henselae and B. quintana. We discuss evidence that surface adhesins are important factors for autoaggregation and biofilm formation by Bartonella species. Finally, we propose that biofilm formation is a critical step in the formation of vegetative masses during Bartonella-mediated endocarditis and represents a potential reservoir for persistence by these bacteria.
153 citations
Cites background from "Intruders below the Radar: Molecula..."
...of inoculation of a reservoir host by Bartonella species (223, 224)....
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...stealthy nature of these pathogens (223)....
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TL;DR: A One Health approach to bartonellosis and other zoonotic infections is needed to properly address animal health, public health, and environmental factors that influence the distribution and transmission of these bacteria.
Abstract: In recent years, an increasing number of Bartonella species have been identified as zoonotic pathogens, transmitted by animal bites, scratches, arthropods and even by needle sticks. Considering the diversity of newly discovered Bartonella species and subspecies and the large number and ecologically diverse animal reservoir hosts and the evolving spectrum of arthropod vectors that can transmit these bacteria among animals and humans, the clinical and diagnostic challenges posed by Bartonella transmission in nature are presumably much more complex than is currently appreciated by diagnosticians, vector biologists, ecologists, physicians, or veterinarians. Historically the term "bartonellosis" was attributed to infections with Bartonella bacilliformis, transmitted by sandflies in the Peruvian Andes. Currently, however, bartonellosis now includes infections caused by any Bartonella sp. anywhere in the world. Potentially, because Bartonella spp. can infect erythrocytes, endothelial cells, pericytes, CD34(+) progenitor cells, and various macrophage-type cells, including microglial cells, dendritic cells, and circulating monocytes in vitro, the clinical and pathological manifestations of bartonellosis appear to be very diverse in both sick animals and human patients. Because 75% of emerging infectious diseases are zoonoses, many of which are vector-transmitted by an arthropod, a One Health approach to bartonellosis and other zoonotic infections is needed to properly address animal health, public health, and environmental factors that influence the distribution and transmission of these bacteria. The One Health concept encourages a spirit of cooperation among animal, environmental, and human health professionals and promotes developing integrated solutions for complex problems that impact the health of animals, humans, and the planet. Importantly, substantial research is needed to define the medical importance of this genus as a cause of animal and human illnesses.
116 citations
Cites background or result from "Intruders below the Radar: Molecula..."
...Studies from Christoph Dehio’s research group have shown that a laterally acquired type IV secretion system (T4SS; Trw) diversified among the Bartonella lineages to facilitate host-restricted adhesion to erythrocytes in a wide range of mammals (Harms and Dehio 2012)....
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...may establish infection internal to red blood cells in a species-specific manner, but the ability to invade other cell types does not appear to be as restrictive (Harms and Dehio 2012; Houchaima et al. 2013)....
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...Seventeen Bartonella spp. have been associated with an expanding spectrum of animal and human diseases (Breitschwerdt et al. 2010a; Harms and Dehio 2012; Kaiser et al. 2011)....
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...berkhoffii to induce the production of VEGF and resultant vasoproliferation of endothelial cells (Beerlage et al. 2012; Harms and Dehio 2012; Kaiser et al. 2011)....
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...…immune response by remaining undetectable 54 ILAR Journal by guest on June 17, 2014 http://ilarjournal.oxfordjournals.org/ D ow nloaded from by Toll-like receptor 4, which, when activated by LPS from other Gram-negative bacteria, results in a strong inflammatory response (Harms and Dehio 2012)....
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TL;DR: The present review explores the interrelations within the Bartonella-rodent-flea system and the role of the latter two components is emphasized.
Abstract: Epidemiological studies worldwide have reported a high prevalence and a great diversity of Bartonella species, both in rodents and their flea parasites. The interaction among Bartonella, wild rodents, and fleas reflects a high degree of adaptation among these organisms. Vertical and horizontal efficient Bartonella transmission pathways within flea communities and from fleas to rodents have been documented in competence studies, suggesting that fleas are key players in the transmission of Bartonella to rodents. Exploration of the ecological traits of rodents and their fleas may shed light on the mechanisms used by bartonellae to become established in these organisms. The present review explores the interrelations within the Bartonella–rodent–flea system. The role of the latter two components is emphasized.
111 citations
Cites background from "Intruders below the Radar: Molecula..."
...Through an apparent double niche, infecting erythrocytes and endothelial cells, bartonellae establish long-term infections in mammalian reservoirs with a silent strategy that prevents their rapid clearance by the host’s immune system (Harms and Dehio 2012)....
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...It has been proposed that these cyclic bacteremic waves are the result of an apparent clearance of the bacteria by the immune system, followed by a new bacterial input from the primary niche to the bloodstream (Harms and Dehio 2012)....
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TL;DR: The recovery of unique clades, uniting Bartonella genotypes from bat flies and bats, supports previous ideas of these flies potentially being vectors for Bartonellae, and suggests vertical transmission across developmental stages.
98 citations
Cites background from "Intruders below the Radar: Molecula..."
...The genus Bartonella comprises facultative intracellular, Gram-negative bacteria, which parasitize erythrocytes or epithelial cells across a range of mammalian hosts, including humans (Mogollon-Pasapera et al., 2009; Chomel and Kasten, 2010; Harms and Dehio, 2012)....
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..., Bartonella quintana [Trench Fever]) (Harms and Dehio, 2012)....
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TL;DR: The culture and characterization of an alphaproteobacterium of the order Rhizobiales, isolated from the gut of the honey bee Apis mellifera, and its close phylogenetic position suggest that strain PEB0122T represents a novel species within the genus Bartonella.
Abstract: Here, we report the culture and characterization of an alphaproteobacterium of the order Rhizobiales, isolated from the gut of the honey bee Apis mellifera. Strain PEB0122T shares >95 % 16S rRNA gene sequence similarity with species of the genus Bartonella, a group of mammalian pathogens transmitted by bloodsucking arthropods. Phylogenetic analyses showed that PEB0122T and related strains from the honey bee gut form a sister clade of the genus Bartonella. Optimal growth of strain PEB0122T was obtained on solid media supplemented with defibrinated sheep blood under microaerophilic conditions at 35-37 °C, which is consistent with the cultural characteristics of other species of the genus Bartonella. Reduced growth of strain PEB0122T also occurred under aerobic conditions. The rod-shaped cells of strain PEB0122T had a mean length of 1.2-1.8 μm and revealed hairy surface structures. Strain PEB0122T was positive for catalase, cytochrome c oxidase, urease and nitrate reductase. The fatty acid composition was comparable to those of other species of the genus Bartonella, with palmitic acid (C16 : 0) and isomers of 18- and 19-carbon chains being the most abundant. The genomic DNA G+C content of PEB0122T was determined to be about 45.5 mol%. The high 16S rRNA gene sequence similarity with species of Bartonella and its close phylogenetic position suggest that strain PEB0122T represents a novel species within the genus Bartonella, for which we propose the name Bartonella apis sp. nov. The type strain is PEB0122T ( = NCIMB 14961T = DSM 29779T).
82 citations
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