How many Bb strains?

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
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lou
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How many Bb strains?

Post by lou » Fri 24 Jan 2014 15:21

Frequently it is said that there are 100 strains in the U.S., with 300 worldwide. Where is this information cataloged? I have been unable to find it, and don't know how this is determined. In reading various papers, it seems all that exists is individual groups found in one or more geographic locations, and characterized by various means. It is not even clear that the same method of typing gets used, and they produce different results.

Anyone know?

RitaA
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Re: How many Bb strains?

Post by RitaA » Fri 24 Jan 2014 19:04

lou,

To the best of my recollection, the longest list of Borrelia burgdorferi strains that I’ve come across can be found here:

http://www.pasteur.fr/recherche/borreli ... ecies.html

"Strains listed alpha-numerically" points to this link:

http://www.pasteur.fr/recherche/borreli ... betic.html
Alphanumeric list of Borrelia burgdorferi sensu lato strains
A quick count shows there are about 185 entries in that table. Since the table is undated, there could well be a more up-to-date/complete list published elsewhere:

lou
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Re: How many Bb strains?

Post by lou » Fri 24 Jan 2014 21:47

One list at that website shows 31 strains in the U.S. Another shows 43. Since we supposedly only have Bb ss, those numbers ought to match up. And still not anywhere near 100. Seems like the Pasteur site may not be up to date.

I wonder where people are getting the 100 number. Have heard that repeated for years and don't know where it is coming from--the source.

volumi
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Re: How many Bb strains?

Post by volumi » Thu 30 Jan 2014 17:25

Seems like an arbitrary claim.

Very common in Steere and ILADS camps.

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LHCTom
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Re: How many Bb strains?

Post by LHCTom » Thu 30 Jan 2014 20:03

One of the problems is the definition of a strain or species has evolved as the DNA tools have evolved.
Bacteriologists have not yet adopted a concept for a species. Bacterial and archaeal species are defined on the basis of phenotypic properties and whole-genome DNA-DNA hybridization. Each species must have unique phenotypic properties and exhibit more than 70% DNA hybridization among strains. This combination of phenotype and genotype, sometimes referred to as the polyphasic species definition, was a breakthrough in bacterial taxonomy and has served microbiologists very well by stabilizing the field and bringing uniformity to classifying species of Bacteria and Archaea.
With the advent of DNA sequencing, it became possible to analyze how genes evolve and actually see lineages. Initially the highly conserved 16S rRNA gene became the benchmark for defining a species and therefore anything closer is a strain.
Initially there was great anticipation that 16S rRNA gene sequences could be used to define species. However, virtually identical 16S sequences can be found in two organisms that are different species based on the polyphasic definition, so bacterial taxonomists have retained the current definition. Although 16S rRNA gene sequencing cannot differentiate species, it has some benefit in bacterial taxonomy at the species level by placing constraints on what comprises a species. Studies using both DNA hybridization and 16S rRNA gene sequence data illustrate that if two strains show less than 97% 16S rRNA gene sequence similarity, they are separate species. Indeed, Jyoti Keswani and William Whitman at the University of Georgia in Athens find that for most species, similarity values as high as 99% distinguish species with confidence. Therefore, it is unnecessary to carry out the somewhat arduous task of DNA hybridization for those organisms. But, as helpful as this might be for those who have isolated a novel strain, it is of no help in determining what consitutes a species.
So with the use of 16S rRNA gene differences as the method, 97% similarity defined the boundary between species and a strain. More recently, Multi Locus sequencing provides more fidelity by looking at 6-8 housekeeping genes.
Bacteriologists already use PSC to identify clusters of strains of Bacteria and Archaea. For example, Brian Spratt at the Imperial College of London and his collaborators have used multiple locus sequence analyses (MLSA), a phylogenetic approach designed to infer relatedness among strains of various bacterial pathogens. Their approach typically entails choosing five to eight genes depending on the genus of interest. These are sequenced, and the resultant individual gene sequences are linked in tandem, or concatenated, before using them for phylogenetic analysis.
Most recently a B.burgdorferi MLST scheme was developed by Gabriel Margos, Liliana Vitorino, Annie Gatewood, Klara Hanincova ,Klaus Kurtenbach which seems to have been adopted to delineate the various species and strains of Borrelia and is being collected at http://borrelia.mlst.net/ and in NCBI. It is described in various papers and here

http://borrelia.mlst.net/misc/info.asp

http://www.pnas.org/content/105/25/8730.abstract

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725479/

Using 8 carefully chosen housekeeping genes rather than the single 16S rRNA gene, it allows the comparison and analysis of a few thousand nucleotides. It very roughly allows 8 time better resolution in showing the phylogenetic relationship between Borrelia individuals.

Margos et al seems to have taken the lead on trying redefine the many Borrelia organisms using this new more accurate approach. Since this set of housekeeping genes has only been used since about 2008, only Borrelia with these 8 genes sequenced can be categorized with enough resolution to count and identify geographically the various Borrelia Species and Strains within these species done here:

http://pubmlst.org/bburgdorferi/references.shtml
To understand the dynamics of the epizootic spread and to predict the evolutionary trajectories of B. burgdorferi, accurate information on the population structure and the evolutionary relationships of the pathogen is crucial. We, therefore, developed a multilocus sequence typing (MLST) scheme for B. burgdorferi based on eight chromosomal housekeeping genes. We validated the MLST scheme on B. burgdorferi specimens from North America and Europe, comprising both cultured isolates and infected ticks. These data were compared with sequences for the commonly used genetic markers rrs-rrlA intergenic spacer (IGS) and the gene encoding the outer surface protein C (ospC). The study demonstrates that the concatenated sequences of the housekeeping genes of B. burgdorferi provide highly resolved phylogenetic signals and that the housekeeping genes evolve differently compared with the IGS locus and ospC. Using sequence data, the study reveals that North American and European populations of B. burgdorferi correspond to genetically distinct populations. Importantly, the MLST data suggest that B. burgdorferi originated in Europe rather than in North America as proposed previously.
So its not surprising the number of species and strains of Borrelia have not yet been cataloged. If you read the papers by Margos et al and these at http://pubmlst.org/bburgdorferi/references.shtml you will find the best data I'm aware of. The number of strains is potentially much larger than currently cataloged. New species are still being found around the world. But strains can have a single polymorphism ( one nucleotide difference ) and so the number of strains will probably continue to climb every time Borrelia from ticks, hosts and humans is sequenced using this method. The number of strains in each species is probably quite large.
The greater the ignorance, the greater the dogmatism.

Attributed to William Osler, 1902

lou
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Re: How many Bb strains?

Post by lou » Fri 31 Jan 2014 22:41

Thank you for this information. I will try to understand it. Evidently any numbers stated prior to these new developments are suspect, and I still don't know where they came from.

If there is genetic recombination in the field, then doesn't that mean it may be hard to pin these suckers down? Or should I assume that using housekeeping genes or other sequences that don't change as much could be more reliable to separate them. Finding this stuff a bit hard to comprehend. I do think your point about locating more in future is very accurate.

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LHCTom
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Re: How many Bb strains?

Post by LHCTom » Sat 1 Feb 2014 22:13

If there is genetic recombination in the field, then doesn't that mean it may be hard to pin these suckers down? Or should I assume that using housekeeping genes or other sequences that don't change as much could be more reliable to separate them. Finding this stuff a bit hard to comprehend. I do think your point about locating more in future is very accurate.
The 8 housekeeping genes were selected because they are "essential" for metabolism and change fairly uniformly and not in plasmids which can be horizontally transfered between strains, species and even other bacteria. The plasmid exchange between say B burgorferi and B Garinii or a relapsing group like B miyamotoi can lead to fairly quick changes without the ussual environmental pressures of evolution. The plasmids take up about 40% of the total genmeome in Bb. This differs across all species. A new or lost plasmid would probably only be noticed if the entire genome were sequenced since there are favorite genes commonly used that are useful without the cost of full sequencing. If you look at the total number of base pairs ( nucleotides) in the various Borrelia, they vary by large numbers. This is in part due to taking on and losing entire new plasmids. Plasmid loss is one of the mechanisms that may be responsible for Bb becoming non-cultivable. Plasmid content also has been tied to infectivity. So these little buggers are tricky. The Bb main chromosone has 853 genes or 59% which are not subject to horizontal plasmid transfer or plasmid loss. Lose the Chromosone and you die.
Borrelia burgdorferi strain B31 (Bb), one of a group of closely related spirochetes that cause Lyme disease (1), has a genome consisting of a linear chromosome of 910,724 base pairs (2) and 21 linear and circular plasmids containing over 610,694 base pairs (plus unsequenced telomere regions) (3). The chromosome contains 853 predicted genes, of which 500 (59%) have predicted functions based on amino acid sequence similarity with orthologous gene products (2). The 535 putative gene products encoded by the B. burgdorferi plasmids are predominantly of unknown function and include many paralogous gene families (2, 3). Comparison of the plasmid profiles of Lyme disease spirochetes, including B. burgdorferi, Borrelia afzelii, and Borrelia garinii, demonstrates that a high degree of heterogeneity and plasticity exists in terms of plasmid content (4).

Considerable evidence indicates that Bb plasmids are important in pathogenesis. In vitro passage of Bb is associated with loss of plasmids (5). Plasmid loss after 10–17 passages is also coupled with decreased infectivity in mice and changes in spirochetal protein expression (6–9). High- and low-infectivity phenotypes of Bb coexist in an uncloned population, but the proportion of high-infectivity phenotypes decreases with serial in vitro passage (10). Plasmid profiles vary among certain Bb sensu lato strains (including Bb sensu stricto, B. garinii, and B. afzelii) as well as within high- and low-passaged cultures; this variance is associated with infectivity of Bb in mice (5, 9–13).
The greater the ignorance, the greater the dogmatism.

Attributed to William Osler, 1902

ChuckG
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Re: How many Bb strains?

Post by ChuckG » Sun 2 Feb 2014 0:15

Lumpers and splitters
Lumping and splitting are opposing tendencies in any discipline which has to place individual examples into rigorously defined categories. The lumper/splitter problem occurs when there is the need to create classifications and assign examples to them, for example schools of literature, biological taxa and so on. A "lumper" is an individual who takes a gestalt view of a definition, and assigns examples broadly, assuming that differences are not as important as signature similarities. A "splitter" is an individual who takes precise definitions, and creates new categories to classify samples that differ in key ways.

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