Brian Stevenson Ph.D. spirochete lab

Enterococcus faecalis modulates phase variation in Clostridioides difficile

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an hourglass with the words " days of our lives " on it ALT: an hourglass with the words " days of our lives " on it

Like sand through an hourglass...

a woman in a blue and white dress is holding a dog and saying people come and go so quickly here . ALT: a woman in a blue and white dress is holding a dog and saying people come and go so quickly here .

I'm pleased to have helped Jen and Brandon in their very successful career paths!

Correction to the article, though. Jen Miller and Brandon Jutras never worked together in my lab at U Kentucky. Jen left in 2005, and Brandon didn't arrive until 2008.

@jutraslab.bsky.social

How small can you go?

“Convergent extreme reductive evolution in ancient planthopper symbioses”

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a picture of a lion with the words " remember the good old days " below it ALT: a picture of a lion with the words " remember the good old days " below it

Just dug out a cloned fragment of B burgdorferi cp32-1, which we used for restriction mapping the genome back in 1996

We were working in the dark, back before the B burgdorferi genome had been sequenced.

#PostDocDays
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Congratulations!!

Figure 2. qPCR data of B. mayonii (blue dots) and B. burgdorferi (red dots) with mean spirochetemia as a bar in SCID mice at 7, 14, 21, and 28 dpi (n=4 per infection group). At 7 dpi, three B. mayonii-infected SCID had undetectable levels of spirochetes in the blood, thus only one dot is present with no mean bar. X-axis is days post-inoculation. Y-axis is copies of flaB per mL of blood. Unpaired t test with Welch’s correction was used to compare means at each timepoint. 7 dpi p=0.0333. 14 dpi p=0.0468. 21 dpi p=0.2782. 28 dpi p=0.3606. * p<0.05, ns, not significant.

Borrelia mayonii induces carditis but not arthritis in Lyme-susceptible mice

from Cleveland, Wijetunga, Casselli, Tourand, Pecoraro, and Brissette
@brissettelab.bsky.social

www.frontiersin.org/journals/imm...

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The again, in the USA, I never order tea at restaurants. It is always a stale teabag soaking in lukewarm water 🤢

When visiting relatives in the UK, I’ve learned never to accept an offer of “coffee”. It is invariably instant coffee 🤢

Starvation-independent alarmone production inhibits translation through GTP depletion in Bacillus

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a group of older men are sitting around a table and one of them is saying i feel younger ALT: a group of older men are sitting around a table and one of them is saying i feel younger

You're not that much younger, me lad!

Seema Mattoo on Bordetella pertussis and whooping cough!

Matters Microbial,
@mattoolab.bsky.social
@markowenmartin.bsky.social

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a man making a face in front of a sign that says forever star ALT: a man making a face in front of a sign that says forever star

Need the extra fabric to extend below the crotch, between the legs. Not poking out front, where it would create drag

Screen shot of Rocky Mountain Laboratories in Hamilton, Montana, from the 1937 film "Green Light"

Screen shot of Rocky Mountain Laboratories in Hamilton, Montana, from the 1937 film "Green Light". Location of my postdoc research lab is indicated

Advertisement for the 1937 film "Green Light"

Screen shot of Rocky Mountain Laboratories in Hamilton, Montana, from the 1937 film "Green Light"

Postdoc memories (sort of)

"Green Light", 1937, is partially set in the Bitterroot Valley, Montana, deals with tick-borne disease. It includes shots of my old lab home at Rocky Mountain Labs, Hamilton. The lab itself looks almost identical to when I was there, 1994-1998. The film stars Errol Flynn.

Perhaps.
Need to study expression patterns of the multiple ospC loci. Are all functional?

Neighbor-joining tree of the ParA-like proteins encoded on cp32 elements. The tree was constructed from all the proteins encoded by the parA-like genes of the cp32s of the sequenced B. burgdorferi sensu lato genomes and those known from strains CA15, Sh-2-82, and Far04. Numbers on the tree branches are bootstrap support values from 1,000 trials. Blue and yellow boxes highlight the different sequence types (tree branches) for the cp32 ParA proteins. These types correlate with episomes named in large red type. The species which harbored each cp32 are indicated by the color of the strain name at the right branch tips (see color key in upper left of figure). The DN127 protein labeled DN127frag in the cp32-12 branch is a ParA fragment from the DN127 cp32-Quad element. All the replicons in the figure carry highly related complements of non-partition cluster genes, except for seven “lp32” plasmids, noted by a pink background in the figure, which encode cp32-like ParA proteins but do not carry erp sequences (these will be described elsewhere [S. Casjens, unpublished data]). Replicon cp26 is an unrelated, universally present circular “plasmid” and is shown only for reference. Bar, 0.05 fractional change.

See also:
Distribution of cp32 Prophages among Lyme Disease-Causing Spirochetes and Natural Diversity of Their Lipoprotein-Encoding erp Loci
journals.asm.org/doi/10.1128/...

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Whole-Genome Sequences of Borrelia bissettii, Borrelia valaisiana, and Borrelia spielmanii | Journal of Bacteriology ABSTRACT It has been known for decades that human Lyme disease is caused by the three spirochete species Borrelia burgdorferi, Borrelia afzelii, and Borrelia garinii. Recently, Borrelia valaisiana, Bo...

DN127, also for California, has a plasmid that consists of 4 different cp32s!

journals.asm.org/doi/10.1128/...

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a girl in a red dress is standing in front of a scale that says good on it ALT: a girl in a red dress is standing in front of a scale that says good on it

Because every reviewer should think that MY proposal is the best ever, and should give it a really good score!

Comparative genomics of Borrelia lusitaniae Abstract. Human Lyme disease is a frequent tick-borne human disease that is caused by several species in the Borrelia burgdorferi sensu lato (BBSL) clade o

Comparative genomics of Borrelia lusitaniae

Complete genome sequences of three isolates. Each has very few plasmids. A most unusual feature is that their important cp26 plasmids are partially degraded dimers, carrying multiple, distinct ospC genes.

academic.oup.com/g3journal/ad...

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TBDRP banner, showing: Gloved hand with blood sample Three ticks on a human hand Family walking in the woods

The new US budget includes funding for the Tick-Borne Disease Research Program of the CDMRP.
Details on the program and requests for applications to be announced soon.

cdmrp.health.mil/pubs/press/2...

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Yes

From the paper: Figure 10. Proposed model of VM protein-mediated disruption of cell-cell junctions. In non-infected cells (on the left), tight junctions (JAM, Occludin and Claudin) and adherens junctions (Cadherin) stabilize cell-cell junctions while ZO/Cadherin proteins connect junctions and actin cytoskeleton. During leptospiral infection (on the right), L. interrogans induces the expression and secretion of two virulence-modifying (VM) proteins, LIMLP_11655 and LIMLP_11660. These proteins would interact directly with host epithelial cells, very likely by binding of their Ricin B domain to lectin receptors present at the host cell surface. The VMs could be then internalized within the host cell, where they trigger an increase in intracellular calcium levels. This calcium deregulation would activate the calmodulin-MLCK pathway, leading to actin cytoskeleton remodeling and ultimately disassembly of tight and adherens junctions. The resulting loss of barrier integrity facilitates L. interrogans transmigration across epithelial and endothelial cell layers, promoting systemic dissemination to target organs, such as liver and kidneys.

Leptospira interrogans produces effectors, structurally related to toxin-like proteins, that modulate calcium homeostasis and disrupt cell-cell junctions, thereby allowing translocation across epithelium barriers, tissue colonization and pathogenicity.

pubmed.ncbi.nlm.nih.gov/41634022/

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From the paper: Deeply divergent Treponema pallidum lineage in the Americas and implications for pathogen evolution. We identified and reconstructed a ~5500-year-old 1.7× T. pallidum genome (TE1-3) from a Middle Holocene individual at Tequendama I rock shelter in Colombia. Phylogenomic analysis reveals that TE1-3 is an early-branching sister lineage to all extant T. pallidum subspecies, with divergence dating to ~13,700 years ago (95% HPD: 6768 to 20,592 cal yr B.P.) and coinciding with early human migration and ecological shifts in the Americas. Despite its antiquity, TE1-3 possesses the T. pallidum virulence-associated genes, suggesting conserved pathogenic capacity. TE1-3 provides the earliest molecular evidence of T. pallidum in the Americas to date, bridging a multimillennial gap between skeletal signs and genomic data and offering a rare glimpse into the long-term evolution of treponemal pathogens.

A 5500-year-old Treponema pallidum genome from Sabana de Bogotá, Colombia

"This genome falls outside of known T. pallidum lineages today, but it has many genetic hallmarks associated with virulence in modern pathogens of these subspecies"

Science
pubmed.ncbi.nlm.nih.gov/41570125/

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Congratulations!

I don't know who has won the most trivia nights. We only hear the complaints of those who never win (Linden!). And can confirm that the spirochete researcher who raked in $$$ on Jeopardy has never yet won a trivia night!

It's a shame that research has continued to focus on OspA, instead of new approaches with targets that are produced during mammalian infection and that take advantage of the anamnestic response.
Like all other vaccines.

The old and upcoming human vaccines, and the current animal OspA vaccines, work only if the blood has a high titer of anti-OspA antibodies at the time of tick bite. Which is a fairly narrow window of time. When titers decline, the vaccine is not protective.

And so the major surface protein in cultured B. burgdorferi, OspA, was thought to be a major antigen during mammalian infection. Leading to development of vaccines based on OspA. In truth, OspA is not produced during mammalian infection.

Borrelia burgdorferi receive a mix of signals from culture medium. So they simultaneously produce tick-specific and mammal-specific proteins.
And do not produce some mammal-specific proteins in culture, such as CspZ (which is showing promise as a vaccine)

For example, initial approaches to developing a Lyme vaccine were naive, and did not consider that the bacteria are living organisms that adapt to their environments.
Importantly, the protein profile in culture does not correspond with expression levels at any point in the natural infectious cycle.