Multi-Locus Sequence Analysis Reveals Profound Genetic Diversity among Isolates of the Human Pathogen Bartonella bacilliformis

Abstract

Bartonella bacilliformis is the aetiological agent of human bartonellosis, a potentially life threatening infection of significant public health concern in the Andean region of South America. Human bartonellosis has long been recognised in the region but a recent upsurge in the number of cases of the disease and an apparent expansion of its geographical distribution have re-emphasized its contemporary medical importance. Here, we describe the development of a multi-locus sequence typing (MLST) scheme for B. bacilliformis and its application to an archive of 43 isolates collected from patients across Peru. MLST identified eight sequence types among these isolates and the delineation of these was generally congruent with those of the previously described typing scheme. Phylogenetic analysis based on concatenated sequence data derived from MLST loci revealed that seven of the eight sequence types were closely related to one another; however, one sequence type, ST8, exhibited profound evolutionary divergence from the others. The extent of this divergence was akin to that observed between other members of the Bartonella genus, suggesting that ST8 strains may be better considered as members of a novel Bartonella genospecies.

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

“…Bartonella bacilliformis exhibits strong LD, corroborated by MLST, AFLP and Infrequent Restriction Site PCR (Chaloner et al, 2011). In this species, the MLG ST 1 has been sampled repeatedly at various places in Peru from 1960 to 2007.…”

“…In this species, the MLG ST 1 has been sampled repeatedly at various places in Peru from 1960 to 2007. ST8 has been sampled twice 150 km and 9 years apart, in spite of an inferred 'strong influence of recombination' (Chaloner et al, 2011).…”

Molecular Typing of “Candidatus Bartonella ancashi,” a New Human Pathogen Causing Verruga Peruana

“…B. bacilliformis infections are seen only in the Andes mountain region of Peru, Ecuador, and Columbia (2,500 to 8,000 feet above sea level) (3,4). Although B. bacilliformis was the first Bartonella species discovered, over 100 years ago, and is a pathogen causing significant morbidity and mortality, our understanding of this pathogen and the causes of Carrion's disease are rather limited (2,(4)(5)(6). Currently, B. bacilliformis is the only agent definitively identified to cause Carrion's disease, though Bartonella rochalimae caused an Oroya fever-like illness in a traveler returning from Peru (2,4,6).…”

“…To more fully characterize "Candidatus Bartonella ancashi," the initial isolate (20.00) and the second isolate (20.60) were subjected to gene sequencing, MLST, and MST. MLST and MST techniques are used in the differentiation of Bartonella species and strains (5,8,9). MLST is useful for the detection of novel Bartonella species, while MST is useful for uncovering genetic differences between strains (5, 8, 9).…”

“…ITS sequences are highly variable between strains of the same species and are able to provide more insight into the genetic diversity and relatedness of genotypes within a species (1). B. bacilliformis isolates cluster in close proximity to each other, with the exception of B. bacilliformis isolate LA6.3, which belongs to a highly divergent group of B. bacilliformis isolates, strain type 8 (5). "Candidatus Bartonella ancashi" is located on an isolated branch away from the B. bacilliformis isolates, including B. baciliformis isolate LA6.3, and away from B. isolates, Bartonella rochalimae, and the next-most-closely related Bartonella species, Bartonella clarridgeiae.…”