A simple method to detect Borrelia burgdorferi sensu lato proteins in different sub-cellular compartments by immunofluorescence

Brock, Aaron M; Jutras, Brandon L.

doi:10.1016/j.ttbdis.2021.101808

Cited by 5 publications

(3 citation statements)

References 79 publications

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“…Our work has shown that many of the advances in the field of Borreliae cell biology, such as quantitative microscopy and automated cell detection, can now be applied to study the syphilis spirochete, despite the dramatic differences in helical pitch (Figs. 1 and 5 ) 38 , 76 – 79 . These tools were paramount in determining that unlike the Lyme and relapsing fever Borrelia , which elongate by synthesizing heritable zones of PG, T. pallidum cell wall synthesis is lateral (Fig.…”

Section: Discussionmentioning

confidence: 99%

A large screen identifies beta-lactam antibiotics which can be repurposed to target the syphilis agent

Hayes

Dressler

Norris

et al. 2023

npj Antimicrob Resist

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Syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (hereafter called T. pallidum), is re-emerging as a worldwide sexually transmitted infection. A single intramuscular dose of benzathine penicillin G is the preferred syphilis treatment option. Both supply shortage concerns and the potential for acquired antibiotic resistance further the need to broaden the repertoire of syphilis therapeutics. We reasoned that other β-lactams may be equally or more effective at targeting the disease-causing agent, Treponema pallidum, but have yet to be discovered due to a previous lack of a continuous in vitro culture system. Recent technical advances with respect to in vitro T. pallidum propagation allowed us to conduct a high-throughput screen of almost 100 β-lactams. Using several molecular and cellular approaches that we developed or adapted, we identified and confirmed the efficacy of several β-lactams that were similar to or outperformed the current standard, benzathine penicillin G. These options are either currently used to treat bacterial infections or are synthetic derivatives of naturally occurring compounds. Our studies not only identified additional potential therapeutics in the resolution of syphilis, but provide techniques to study the complex biology of T. pallidum—a spirochete that has plagued human health for centuries.

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Section: Discussionmentioning

confidence: 99%

A large screen identifies beta-lactam antibiotics which can be repurposed to target the syphilis agent

Hayes

Dressler

Norris

et al. 2023

npj Antimicrob Resist

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“…The serum was then removed, pooled together, and frozen at -20ºC. The specificity of the antibody was tested using immunofluorescence and was found to bind S. mutans, D. radiodurans , S. aureus , and E. coli PG (data not shown) using methods described elsewhere [ 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

Peptidoglycan in osteoarthritis synovial tissue is associated with joint inflammation

Holub,

Wahhab,

Rouse

et al. 2024

Arthritis Res Ther

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Objectives Peptidoglycan (PG) is an arthritogenic bacterial cell wall component whose role in human osteoarthritis is poorly understood. The purpose of this study was to determine if PG is present in synovial tissue of osteoarthritis patients at the time of primary total knee arthroplasty (TKA), and if its presence is associated with inflammation and patient reported outcomes. Methods Intraoperative synovial tissue and synovial fluid samples were obtained from 56 patients undergoing primary TKA, none of whom had history of infection. PG in synovial tissue was detected by immunohistochemistry (IHC) and immunofluorescence microscopy (IFM). Synovial tissue inflammation and fibrosis were assessed by histopathology and synovial fluid cytokine quantification. Primary human fibroblasts isolated from arthritis synovial tissue were stimulated with PG to determine inflammatory cytokine response. Results A total of 33/56 (59%) of primary TKA synovial tissue samples were positive for PG by IHC, and PG staining colocalized with markers of synovial macrophages and fibroblasts by IFM. Synovial tissue inflammation and elevated IL-6 in synovial fluid positively correlated with PG positivity. Primary human fibroblasts stimulated with PG secreted high levels of IL-6, consistent with ex vivo findings. Interestingly, we observed a significant inverse correlation between PG and age at time of TKA, indicating younger age at time of TKA was associated with higher PG levels. Conclusion Peptidoglycan is commonly found in synovial tissue from patients undergoing TKA. Our data indicate that PG may play an important role in inflammatory synovitis, particularly in patients who undergo TKA at a relatively younger age.

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“…Despite concerted efforts to develop effective control tactics, the geographical range of ticks and the incidence of tick-borne diseases continue to grow [3]. In the eastern United States, the blacklegged tick, Ixodes scapularis Say, transmits Borrelia burgdorferi sensu stricto, the Lyme disease spirochete that is primarily responsible for an estimated 476,000 yearly infections [4,5]. This tick also transmits other emerging pathogens for which humans are incidental hosts, including Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, and Powassan Type-2 virus [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Ixodes scapularis Is the Most Susceptible of the Three Canonical Human-Biting Tick Species of North America to Repellent and Acaricidal Effects of the Natural Sesquiterpene, (+)-Nootkatone

Siegel,

Xu,

et al. 2023

Insects

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Ticks are vectors of many human and animal zoonotic disease-causing agents causing significant global health and economic strain. Repellents and acaricides are integral to the human capacity for personal protection from tick bites. Nootkatone, a naturally occurring sesquiterpene found in the Alaskan cedar tree, grapefruit, and other sources, has been documented to be a potent acaricide. Research has also noted repellent effects against some tick species. In this study, our aim was to investigate the effect of synthetic, high-purity (+)-nootkatone on adult Ixodes scapularis, Dermacentor variabilis, and Amblyomma americanum ticks in an in vitro, vertical filter paper bioassay. (+)-nootkatone showed compelling tick repellency, but median effective concentrations (EC50) significantly differed among species. Ixodes scapularis were repelled at very low concentrations (EC50 = 0.87 ± 0.05 µg/cm2). Higher concentrations were required to repel D. variabilis (EC50 = 252 ± 12 µg/cm2) and A. americanum (EC50 = 2313 ± 179 µg/cm2). Significant post-exposure mortality, assessed 24 h after repellency trials, was also observed in I. scapularis but was absent entirely in D. variabilis and A. americanum. These tests demonstrate that nootkatone has a promising dual-action personal protection capacity against adult I. scapularis ticks, warranting further investigation in more natural environments and in the presence of host cues.

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A simple method to detect Borrelia burgdorferi sensu lato proteins in different sub-cellular compartments by immunofluorescence

Cited by 5 publications

References 79 publications

A large screen identifies beta-lactam antibiotics which can be repurposed to target the syphilis agent

A large screen identifies beta-lactam antibiotics which can be repurposed to target the syphilis agent

Peptidoglycan in osteoarthritis synovial tissue is associated with joint inflammation

Ixodes scapularis Is the Most Susceptible of the Three Canonical Human-Biting Tick Species of North America to Repellent and Acaricidal Effects of the Natural Sesquiterpene, (+)-Nootkatone

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