Multilocus Sequence Typing of Borrelia burgdorferi Suggests Existence of Lineages with Differential Pathogenic Properties in Humans

Abstract

The clinical manifestations of Lyme disease, caused by Borrelia burgdorferi, vary considerably in different patients, possibly due to infection by strains with varying pathogenicity. Both rRNA intergenic spacer and ospC typing methods have proven to be useful tools for categorizing B. burgdorferi strains that vary in their tendency to disseminate in humans. Neither method, however, is suitable for inferring intraspecific relationships among strains that are important for understanding the evolution of pathogenicity and the geographic spread of disease. In this study, multilocus sequence typing (MLST) was employed to investigate the population structure of B. burgdorferi recovered from human Lyme disease patients. A total of 146 clinical isolates from patients in New York and Wisconsin were divided into 53 sequence types (STs). A goeBURST analysis, that also included previously published STs from the northeastern and upper Midwestern US and adjoining areas of Canada, identified 11 major and 3 minor clonal complexes, as well as 14 singletons. The data revealed that patients from New York and Wisconsin were infected with two distinct, but genetically and phylogenetically closely related, populations of B. burgdorferi. Importantly, the data suggest the existence of B. burgdorferi lineages with differential capabilities for dissemination in humans. Interestingly, the data also indicate that MLST is better able to predict the outcome of localized or disseminated infection than is ospC typing.

A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

“…Central nervous system manifestations can imitate a broad range of neuropsychiatric syndromes (3), in rare cases even be indistinguishable from acute schizophrenia (4). Borreliosis is caused by a variety of species of Borrelia burgdorferi sensu lato complex, some of which show distinct differences in their pathogenic properties in the human host (5). Borrelia species have a highly complex genomic structure and genetic variation may account for a large proportion of the variability of pathogenicity (6).…”

Lyme Borreliosis - the Utility of Improved Real-Time PCR Assay in Detection of Borrelia burgdorferi Infections

“…Infections of Borrelia burgdorferi sensu lato reveal clinical manifestations affecting numerous organs and tissues, dependent on the different species of Borrelia [3][4][5][6]. The group of spirochetes, usually called Borrelia burgdorferi sensu lato, includes 11 different genospecies, from which 3 are frequently observed in Europe: B. burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii [7,8]. All 3 genospecies of Borrelia are pathogenic in Europe and can be a potential infection agent for specific high risk subjects such as foresters [6,8,9].…”

“…The group of spirochetes, usually called Borrelia burgdorferi sensu lato, includes 11 different genospecies, from which 3 are frequently observed in Europe: B. burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii [7,8]. All 3 genospecies of Borrelia are pathogenic in Europe and can be a potential infection agent for specific high risk subjects such as foresters [6,8,9]. The most common clinical manifestation (80% of infected subjects) of early infection of Borrelia burgdorferi sensu lato is localized erythema migrans, which may be followed by disseminated infection affecting the skin, nervous system, heart or joints before late infection [1,4,10,11].…”

Evolutionary Aspects of Emerging Lyme Disease in Canada

“…Possible mechanisms include genospecies-specific tissue tropism, proliferation, and elicitation of pathology-causing immune responses Arrows indicate pathogenicity as follows: red, STs always (to date) associated with disseminated LD; orange, STs sometimes associated with disseminated LD; green, STs not associated with disseminated LD. Red circles surround clonal complexes of STs that mostly cause disseminated LD, orange circles surround clonal complexes of STs that sometimes cause disseminated LD, and green circles surround clonal complexes of STs that do not (to our current knowledge) cause disseminated LD (27). (64,65,66).…”

“…Second, there is currently no vaccine for humans, and effective public health actions resulting in tick avoidance/infection prevention, targeted at those who are at risk, are paramount for reducing the impact of emerging LD in Canada (26). As the clinical impacts of LD and postinfection immunity are strain specific (21,27), the strain structure of B. burgdorferi in a particular locality will determine the extent to which a local population is at risk from disseminated LD and can suffer multiple reinfections year after year. The ability to identify which strains cause disseminated LD, and to be able to predict their occurrence in Canada by understanding any associations with environmental factors or animal hosts, would permit implementation of preventive public health actions that are "smarter" by targeting the greatest effort at protecting the populations at the greatest risk from severe LD.…”