Welkom bij het Lymeforum

Agents that cause Lyme disease, relapsing fever, leptospirosis, and syphilis belong to the phylum Spirochaetae—a unique lineage of bacteria most known for their long, spiral morphology. Despite the relevance to human health, little is known about the most fundamental aspects of spirochete growth. Here, using quantitative microscopy to track peptidoglycan cell-wall synthesis, we found that the Lyme disease spirochete Borrelia burgdorferi displays a complex pattern of growth. B. burgdorferi elongates from discrete zones that are both spatially and temporally regulated. In addition, some peptidoglycan incorporation occurs along the cell body, with the notable exception of a large region at the poles. Newborn cells inherit a highly active zone of peptidoglycan synthesis at midcell that contributes to elongation for most of the cell cycle. Concomitant with the initiation of nucleoid separation and cell constriction, second and third zones of elongation are established at the 1/4 and 3/4 cellular positions, marking future sites of division for the subsequent generation. Positioning of elongation zones along the cell is robust to cell length variations and is relatively precise over long distances (>30 μm), suggesting that cells ‟sense” relative, as opposed to absolute, cell length to establish zones of peptidoglycan synthesis. The transition from one to three zones of peptidoglycan growth during the cell cycle is also observed in relapsing fever Borrelia. However, this mode of growth does not extend to representative species from other spirochetal genera, suggesting that this distinctive growth mode represents an evolutionary divide in the spirochete phylum.

Significance
Spirochetes pose a significant threat to human and animal health, yet little is understood about how these bacteria grow and divide. We discovered that Lyme disease and relapsing fever spirochetes elongate by synthesizing peptidoglycan, a major component of the cell wall, in discrete zones that are spatially regulated over the cell cycle. Zones of cell growth are established in the previous generation and mark future sites of cell division in the next cell cycle. In contrast, other genera display nearly uniform cell wall synthesis, which is commonly reported in bacteria. The distinctive mode of growth exhibited by the Lyme disease and relapsing fever spirochetes may provide an avenue for the strategic design of targeted antimicrobial therapies

We studied 63 patients with erythema migrans, the pathognomonic cutaneous lesion of Lyme borreliosis, and examined in vitro cultures of biopsies from the active edge of the erythematous patch. Sixteen biopsies yielded spirochetes after prolonged incubations of up to 10.5 months, suggesting that Borrelia burgdorferi may be very slow to divide in certain situations.

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However, at least two well documented cases of Lyme borreliosis have been described which demonstrate that
the infection may relapse in spite of parenteral antibiotic therapy administered over a
time course which would be expected to kill all spirochetes with a cell division cycle of between 6 to 12 h.(Diringer et al, 1987; Case report in New Eng. J. Med., 1988).
Antibiotics are only able to kill actively dividing Borrelia.
If a borrelial cell does not divide at least once during the period of antibiotic therapy, it may persist in the host
and produce relapse or recrudescence of disease.
Therefore, some cases of Lyme borreliosis may require prolonged periods of antibiotic therapy to influence those cell lines of B. burgdorferi with a very slow cycle of cell division.

A Yale team led by Christine Jacobs-Wagner, director of the Microbial Sciences Institute, captured the process via single-cell microscopy. They found that spirochetes showed active synthesis of peptidoglycan—a key component of growth and division—at equally spaced regions along its length (seen here in green). These zones of growth not only defined where the mother cell would divide, but also where future daughter cells would divide as well.
The research is published in the journal Proceedings of the National Academy of Sciences, along with a question-and-answer article in which Jacobs-Wagner discusses the mysteries of bacterial growth and division

Magnuson and co-workers 1948 showed in classic studies that T. pallidum has a remarkably slow dividing time of 30 to 33 hours in infected rabbits.
The dividing time of the bacterium is even slower 38 tot 40 hours in the in vitro tissue culture systems in which limited replication has been achieved (Fieldsteel et al 1981, Norris, 1982

every gene in syfilis is expressed during testicular infection of rabbits.
This gene expression pattern contrasts markedly with that of Borrelia burgdorferi, which undergoes a complex pattern of largely plasmid based differential gene expression as it cycles between arthropod and mammalian hosts