Borrelia spielmanii

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
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Joe Ham
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Borrelia spielmanii

Post by Joe Ham » Tue 24 Feb 2009 18:21

In Vitro Susceptibility of Borrelia spielmanii to Antimicrobial Agents Commonly Used for Treatment of Lyme Disease

http://aac.asm.org/cgi/content/abstract/53/3/1281
http://aac.asm.org/cgi/content/full/53/3/1281#R2
Antimicrobial Agents and Chemotherapy, March 2009, p. 1281-1284, Vol. 53, No. 3
Kristina Morgenstern,1* Georg Baljer,2 Douglas E. Norris,3 Peter Kraiczy,1 Christa Hanssen-Hübner,1 and Klaus-Peter Hunfeld1

ABSTRACT

Ten isolates of the recently delineated genospecies Borrelia spielmanii were tested against antimicrobial agents used to treat Lyme disease and compared to eight isolates of the other three human-pathogenic borrelial genospecies. Despite some small but significant differences in four out of eight antibiotic agents, the susceptibility pattern of B. spielmanii mainly parallels that of the other known human-pathogenic members of the B. burgdorferi sensu lato complex.

[From the full text]
[...]
Isolates belonging to the newly delineated genospecies B. spielmanii have hitherto been isolated from patients in The Netherlands, Hungary, Slovenia, and Germany as well as from ticks in France, Germany, Ukraine, and the Czech Republic (6-8, 18, 19, 23, 25, 28). The heterogeneity of borrelial strains is known to impact the variability of Lyme disease manifestations and clearly is a challenge for the development of diagnostic tests and vaccines (7).
[...]
The in vitro activities of the other antimicrobial agents are summarized in Table 1. On a microgram-per-milliliter basis, the rank order of substances with substantial in vitro activity against the borrelial isolates tested was
clarithromycin (MIC90, 0.0079 µg/ml) >
erythromycin (MIC90, 0.0312 µg/ml) >
ceftriaxone (MIC90, 0.0625 µg/ml) >
doxycycline and cefuroxime (MIC90, 0.25 µg/ml) >
amoxicillin (MIC90, 2 µg/ml).
[...]
It should be considered, however, that although an acquired resistance to antimicrobial agents in borreliae can be detected by use of susceptibility assays (4, 16), in vitro testing alone cannot reliably exclude phenotypic mechanisms of persistence displayed in vivo, as revealed in recent experimental investigations with laboratory animals (2, 10) and clinical studies of patients with Lyme disease (14, 27).
References 2 and 10 go to studies by Hodzic / Barthold, 2002, 2008.
Evidently the authors of this study do not accept the logical fallacy of "non-dividing but infectious spirochetes".

Fin24
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Re: Borrelia spielmanii

Post by Fin24 » Tue 24 Feb 2009 23:54

am I off base in thinking what this means is that

despite in vivo/lab studies showing that pathogens are able to be killed by various drugs; that result still doesnt negate the real possibility that in the host (human body) there still can be peristence of infection due to phenotypic actions??

summary: even though drugs can and do kill the critters in a test tube that doesnt prove that we cant still be ill from them that remain in our bodies despite having taking many abx over a long time

hey Joe--that right???

for those wishing to know what "phenotypic mechanisms" are see first paragraph below, the underlying genetics that possibly control the phenotypical changes is in the 2nd paragraph.

http://www.sciam.com/article.cfm?id=how ... ic-immunit
Scientific American- May 2004--How is Antibiotic Resistance acquired?
From a physical or biochemical perspective, there are a number of factors that contribute to antiobiotic resistance. First, the cell wall of a bacterium can be altered so that an antibiotic cannot penetrate it. Second, some bacteria produce enzymes that can destroy antibiotics before they can work. Third, certain bacteria have developed mechanisms known as efflux pumps, which are able to "eject" antibiotics from the bacterial cell before they have a chance to exert any effect. Finally, the antibiotic target site within the bacteria can be altered. In this situation, when an antibiotic enters the bacterial cell it must bind to its intended target in order to have an effect on the bacteria. If the target within the bacteria has been changed to make this binding impossible, the bacteria will be resistant to the medicine's effects.

Underlying the phenotypic mechanisms of antibiotic resistance are the genetics of antibiotic resistance. Bacteria, like other living organisms, possess DNA that codes for the proteins and enzymes it requires for survival. Changes to the DNA can result in alterations in the final proteins or enzymes, which in turn can lead to antibiotic resistance. A common genetic mechanism for the development of antibiotic resistance is the acquisition of tiny fragments of DNA known as plasmids or transposons. Transposons may code for a specific antibiotic-inactivating enzyme, which, when produced by the bacteria, destroys an incoming antibiotic before it has an opportunity to work. These tiny fragments may be passed directly from one bacterium to another by a process known as conjugation. Alternatively, small viruses may attack certain bacteria and inject DNA fragments by a process known as transduction. SNIP

Joe Ham
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Re: Borrelia spielmanii

Post by Joe Ham » Wed 25 Mar 2009 20:04

I bolded and underlined the word that I consider to be pivotal: phenotypic.
I tend to draw a rather sharp edged distinction between phenotype and genotype even tho they are inextricably linked. Nevertheless, the separation helps us to talk about form vs function. Mazzulli, the author of the link you gave, seems to have a much softer, less precise, notion of the distinction between phenotype and genotype.

Phenotype: the form; observable morphology
Genotype: the function; driven by coding genes
Granted that genotype defines the phenotype of an organism but phenotype is a more restrictive term, narrower, more precise.

Dictionary definitions can help define the parameters:
From The Collaborative International Dictionary of English v.0.48:
phenotype \phenotype\ n. (Biology)
The observable characteristics of an organism, resulting from
the genetic characteristics influenced by a particular
environment. Contrasted with genotype.
[WordNet 1.5 +PJC] phenotypic

From The Collaborative International Dictionary of English v.0.48:
genotype \gen"o*type\ n. (Genetics)
A group of organisms sharing a specific genetic constitution.

2. (Genetics) The genetic constitution of an organism,
specifying the particular alleles at defined loci in the
genome; -- used with respect to one gene, a specific group
of genes, or the entire set of genes within the organism.
Contrasted with phenotype.



Merriam-Webster's Medical Dictionary, © 2002 Merriam-Webster, Inc.
Pleomorphic: able to assume different forms : POLYMORPHIC <pleomorphic bacteria>pleomorphic sarcoma>

The American Heritage® Stedman's Medical Dictionary
pleomorphism:
the existence of irregular and variant forms in the same species or strain of microorganisms, a condition analogous to polymorphism in higher organisms. Pleomorphism is particularly prevalent in certain groups of bacteria and in yeasts, rickettsias, and mycoplasmas and greatly complicates the task of identifying and studying them.
We Lymies tend to use the shorthand term of "L-forms" when talking about these alternate morphologies. It is taken from the Lister Institute which did the pioneering work in the field some 60+ years ago. For us the term includes those recognized forms such as cysts, blebs, CWD, spheroplasts and lastly granules if they are proven infectious and pathogenic. If memory serves that has been done recently by xenodiagnosis but I don't have a reference handy.

The ability of Bb to convert to the L-forms then to revert back to the classic spirochete form is well documented in the Science section of this site in the works by Brorson, MacDonald and others and explained in laymen's terms on the Information page by Tom Grier. [1],[2]
See also the annotated references on Cheryl's site, lymeinfo.net. (Try to ignore the crap on the 'alternative' page.) There are many other references to the ability of Borrelia to adopt alternate morphologies; I just happen to have these links handy.

http://www.lymeinfo.net/medical/LDCysts.pdf
http://www.lymeinfo.net/medical/LDAdverseConditions.pdf
http://www.lymeinfo.net/medical/LDBibliography.pdf

And the 2009 paper by Margulis talking about "round bodies":
http://www1.biogema.de/WEK/312-Margulis-final.pdf


I read the article by Tony Mazzulli in "Scientific American" but found it lacking in rigor. That's the polite way of saying sloppy writing, no supporting evidence, no references. But that lack of rigor is common in newsstand magazines like "Scientific American", "Discover", "Psychology Today" and "Popular Mechanics". They are not, after all, professional journals.

Mazzulli mentions several of Bb's mechanisms of resistance to antibodies and antibiotics such as antigenic variation, efflux pumps, beta-lactamase, binding sites, but those are genotypic mechanisms not phenotypic. That is, the spirochete does not change form while expressing those evasion tactics. Mazzulli, the self-proclaimed "infectious disease specialist", doesn't touch on other evasion tactics of Bb such as intracellular location and sequestration in tendons and the brain where it is beyond the reach of antibodies and most antibiotics. But enough about Mazzulli; he just doesn't understand all that he knows about bacterial resistance, and he doesn't know enough.

On the other hand, maybe Morgenstern and Hunfeld don't either.
I interpreted "phenotypic mechanisms of persistence" as an acknowledgment of L-forms and as a poke in the eye to IDSA's complete stonewall on this issue. But a reading of some papers by Hunfeld doesn't support that notion and so it appears that I was wrong. It looks like there is no support to be had from Morgenstern and Hunfeld on the issue of L-forms as a method of persistent infection. They can maybe see what they are looking at but not know what it means. Maybe they also believe that there are such things as "non-dividing but infectious spirochetes."

Fin24
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Joined: Sat 8 Mar 2008 20:14

Re: Borrelia spielmanii

Post by Fin24 » Wed 25 Mar 2009 20:46

Mazzulli mentions several of Bb's mechanisms of resistance to antibodies and antibiotics such as antigenic variation, efflux pumps, beta-lactamase, binding sites, but those are genotypic mechanisms not phenotypic. That is, the spirochete does not change form while expressing those evasion tactics
teeny tiny commonly made error

PHENOTYPE aint just shape its also BEHAVIOR
as such efflux pumping while genetically programmed--the animals' choice of when to do it IS phenotypical behavior!!

the problem can arise with semantic when you try to use vernacular dictionary defs instead of " scientific usages"

you cant actually separate form and function BUT both of those can be somewhat separated from genetic programming for either or both.

Mazulli's softer separation of geno and pheno are both acceptable and commonly agrred to--for about 2-3 decades as the whole nature vs nurture and epigenetics fields exploded

for example we now know that genes arent destiny and that environmental influences CAN and DO change the genes ( Lamarckian almost)--epigenetics is fascinating and hard to fathom often

but basically it means that there are no longer the strong demarcations you prefer and its a circular, overlapping spiral of cause and effect between genes and phenotypic expression of those genes ( form , function and behavior) that is not static.

unfortunately "pheno" isnt strict and NOT just the form or shape
heres a bilogy dictionary def of phenotype edited to add
http://www.biology-online.org/dictionary/Phenotype

1) The physical appearance or biochemical characteristic of an organism as a result of the interaction of its genotype and the environment.

(2) The expression of a particular trait, for example, skin color, height, behavior, etc., according to the individual’s genetic makeup and environment


there does NOT have to be a change in form--just in behavior--to be phenotypical!! so Mazzuli wasnt wrong--sorry

youre observations re SciAm are correct--we in academics do NOT classify them as "primary" or "solid" sources but instead "gray" sources along with newpapers etc BUT theyre great for getting the verbags down a notch to more understandeable ( altho even many lay folks still have problems and prefer People mag for their science news)


the only primary source are original studies and reviews--I am updating a lecture about what makes a good source or study and how to analyze them and will post here soon
Last edited by Fin24 on Wed 25 Mar 2009 22:15, edited 1 time in total.

Joe Ham
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Re: Borrelia spielmanii

Post by Joe Ham » Wed 25 Mar 2009 22:10

We could split hairs about what constitutes a behavioral phenotype but without a source of reference for your definition that would be just whizzing into the wind.

Fin24
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Re: Borrelia spielmanii

Post by Fin24 » Wed 25 Mar 2009 22:26

sorry about forgetting to place the cite--so edited my dear ( I wouldnt want you to catch cold whizzing in the wind--I hear it causes " shrinkage" :o )

here are other references too

even wiki
http://en.wikipedia.org/wiki/Phenotype
A phenotype is any observable characteristic or trait of an organism: such as its morphology, development, biochemical or physiological properties, or behavior
http://www.everythingbio.com/glos/defin ... =phenotype
physical characteristics and observable attributes( including behaviors),

http://www.bio-medicine.org/biology-def ... Phenotype/
total physical appearance and CONSTITUTION ( lets not quibble over the definition of this too)

we used to tell the kids" the programming is the genotype and the way it is eventually expressed or used is the phenotype--and also--the blueprint plans is the genotype, the finished house is the phenotype( color of house and the rooms' accessories, and change of use like if the bathroom is used to shower or to read in, instead of the library) ,just because the plans say " bathroom" doesnt mean itll be used that way
simplifications to be sure but did the trick


enough??? on Biology I can rarely be challenged--despite always double checking myself due to CRS disease this crap I eat and poop in my sleep!!! there's just so many classes you can teach to premeds and nursing students before you have it forever tattooed in your brain!!!

Joe Ham
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Re: Borrelia spielmanii

Post by Joe Ham » Thu 26 Mar 2009 0:52

Ah, you like Wiki for scientific reference. Maybe you you would like this page:
http://wiki.answers.com/Q/Whatis_the_di ... _phenotype
Phenotype, This is the "outward, physical manifestation" of the organism
Genotype, This is the "internally coded, inheritable information"

From Stanford:
http://plato.stanford.edu/entries/genotype-phenotype/
The phenotype of an organism is the class to which that organism belongs as determined by the description of the physical and behavioral characteristics of the organism, for example its size and shape, its metabolic activities and its pattern of movement.

The genotype is the descriptor of the genome which is the set of physical DNA molecules inherited from the organism's parents. The phenotype is the descriptor of the phenome, the manifest physical properties of the organism, its physiology, morphology and behavior.

The concepts of phenotype and genotype also demand the distinction between types and tokens. As the words “genotype” and “phenotype” suggest, these are types, sets of which any given organism and its genome are members, sets defined by their physical description. Any individual organism and its genome are members of those sets, tokens of those types.
Would it be productive to belabor the term behavior?
I might say that the spirochetal morphology is phenotypical. You might say that its swimming behavior is also phenotypical. And yet the same Borrelia in the cyst form cannot swim. So what would be the correct term to describe how the change of form results in the change of function (behavior)?
enough??? on Biology I can rarely be challenged...
I took a few courses on Biology in school, maybe one of them was taught by you, maybe that's why I'm so screwed up.

On your professional professionalism: May I remind you that Noah's Ark was built and sailed by amateurs, the Titanic by professionals.

But we are way off topic here. Would you care to start another -- maybe in the Cafe?

Fin24
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Joined: Sat 8 Mar 2008 20:14

Re: Borrelia spielmanii

Post by Fin24 » Thu 26 Mar 2009 3:32

all I was saying is you cant get too strict on your limitations of definitions if they exclude commonly accepted terminologies

even YOUR cites do say
its metabolic activities and its pattern of movement
its physiology, morphology and behavior

Would it be productive to belabor the term behavior
NO--anything can be placed into that category as long as it refers to ACTIONS of the organism

again your confusion may be about making things to constrained
it is indeed as correct to say swimming IS phenotypical--for that stage or body morph

and that other behaviors are as phenotypical for OTHER body forms of the same animal

as a biologist I have NO problem accepting the fluidity of definitions and that theyre situational

and the ASSUMPTIVE outcome is that most times change of form confers change of function--it doesnt HAVE TO, it just sometimes DOES
So what would be the correct term to describe how the change of form results in the change of function (behavior)?
what I would tell a student is to investigate the " relationships between morphology and function" in development ( embryology) and in physiology and in evolution
morphology is "structure" and that can dictate the range of functional activities/behaviors, and behavior can also change form/morphologies

there are "morphologically determined functions" and "indeterminate functions" meaning that some function are limited to the morphology ( former) and some are not (latter) and all functions, beahviors, actions are part of that "phenotype"

from a purely bio/microbio point of view: behaviors are aggregates of the responses or reactions or movements made by an organism in any situation.( biology online)

any response, reaction, or movement(action) is a "behavior" and those behvaiors are part of the "phenotype"

as for wiki I dont "like" it nor do I accept it as a "black source" BUT it was verified by other reputable sources and what I meant was " even wiki" had the same viewpoint as in not necessarily only by science types.
maybe one of them was taught by you, maybe that's why I'm so screwed up
Id bet on it!!! :lol:
Would you care to start another -- maybe in the Cafe?

Ill follow you anywhere (kiss)

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