metal requirements of Bb - dead end

[Guest guest]

" Successful colonization of the human host by bacterial pathogens

requires that bacteria overcome strict iron (Fe) limitations

imparted by the host (1, 2). In humans, the amount of free Fe (~10^-

18 M) (3) is well below the levels required to support the growth of

most bacteria (10^-6 to 10^-7 M) (4). At the onset of infection,

host cells increase the production and secretion of lactoferrin to

limit further available Fe and inhibit bacterial growth (5). To

overcome this Fe restriction, pathogenic bacteria have developed

specialized systems that aid in the acquisition and assimilation of

Fe. However, this does not seem to be the case for Borrelia

burgdorferi. "

http://www.sciencemag.org/cgi/content/full/288/5471/1651#T2

I knew Bb used Mn in place of Fe. I've just been learning in chem

about chelators... and had a faint brainstorm that maybe excretion

of host Mn could harm Bb and be responsible for some clinical

findings re chelation... or whatever. Interestingly, it appears that

the human requirement for Mn may be rather low, as pubmed gives the

impression that symptomatic deficiency is rare.

However, it appears that unlike L. plantarum, which also requires no

Fe, Bb does not contain a great deal of Mn, tho it does require Mn

for growth:

" Expressed as nanomoles of metal per milligram of protein

Mg Ca Mn Fe

E. coli 146 46 0.79 4.2

T. denticola 71 35 0.24 3.5

L. plantarum 120 4.5 150 < 0.05

B. burgdorferi 94 43 1.9 < 0.05 "

The article doesnt mention whether the mammal sequesters Mn as it

does Fe. Presumably not, tho who knows if anyone has ever tried to

find out.

" Mean values in serum for Mg were 1.72 µg/l (± 0.19) for [human]

controls " and slightly higher for diabetics. I cant figure out how

much of that may be free or bioavailable to bacteria.

http://www.ams.ac.ir/AIM/0033/nour0033.html

Bastards! What *do* they need? I wonder if their Fe non-requirement,

unique amongst pathogenic bx, is quite significant in their

successful persistance. Other bx fight Fe sequesteration using Fe-

acquiring proteins called siderophores, obviously with some success,

but perhaps at a cost both in energy and stealth.

I wonder if any of the special non-metal-containing Bb metabolic

enzymes are particularly free of any human analogues and might

therefore make suitable high-specificity drug targets - jes' a meek

brainstorm from yers truly, tho I dont know the first thing about

bacterial metabolic enzymes and their analogicity.