Biofilm formation by<i>Borrelia burgdorferi</i>sensu lato

Timmaraju, Venkata Arun; Theophilus, Priyanka A. S.; Balasubramanian, Kunthavai; Shakih, Shafiq; Luecke, David F.; Sapi, Eva

doi:10.1093/femsle/fnv120

Cited by 32 publications

(50 citation statements)

References 37 publications

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“…When we evaluated the possibilities that observed Borrelia aggregates are indeed biofilm structures, its important biofilm traits like structural rearrangements and changes in development on different substrate matrices as well as the different components of the extracellular protective polymeric surface were studied [32, 33]. Our atomic force microscopic results provided evidence that, at various stages of aggregate development, rearrangements take place at multiple levels that lead to a continuously complex rearranging structure [32].…”

Section: Introductionmentioning

confidence: 99%

“…When the EPS of the aggregates was studied for potential exopolysaccharides, both sulfated and non-sulfated/carboxylated substrates were found; however, the majority was non-sulfated polymucosac-charide alginate. We provided evidence that the Borrelia EPS matrix also contains calcium and extracellular DNA [32, 33]. …”

Section: Introductionmentioning

confidence: 99%

“…Several previously described Borrelia biofilm markers such as sulfated/non-sulfated poly-saccharides, alginate, extracellular DNA, and calcium were analyzed using immunohistochemistry and different staining techniques such as Spicer–Meyer, Alizarin, and extracellular DNA staining methods [32, 33]. The obtained results were visualized using various microscopic techniques such as dark and bright field, fluorescent, and differential interference contrast microscopy.…”

Section: Introductionmentioning

confidence: 99%

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Effect of RpoN, RpoS and LuxS pathways on the biofilm formation and antibiotIc sensitivity of Borrelia burgdorferi

Sapi¹,

Theophilus²,

Pham³

et al. 2016

EuJMI

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Borrelia burgdorferi, the causative agent of Lyme disease, is capable of forming biofilm in vivo and in vitro, a structure well known for its resistance to antimicrobial agents. For the formation of biofilm, signaling processes are required to communicate with the surrounding environment such as it was shown for the RpoN–RpoS alternative sigma factor and for the LuxS quorum-sensing pathways. Therefore, in this study, the wild-type B. burgdorferi and different mutant strains lacking RpoN, RpoS, and LuxS genes were studied for their growth characteristic and development of biofilm structures and markers as well as for their antibiotic sensitivity. Our results showed that all three mutants formed small, loosely formed aggregates, which expressed previously identified Borrelia biofilm markers such as alginate, extracellular DNA, and calcium. All three mutants had significantly different sensitivity to doxycyline in the early log phase spirochete cultures; however, in the biofilm rich stationary cultures, only LuxS mutant showed increased sensitivity to doxycyline compared to the wild-type strain. Our findings indicate that all three mutants have some effect on Borrelia biofilm, but the most dramatic effect was found with LuxS mutant, suggesting that the quorum-sensing pathway plays an important role of Borrelia biofilm formation and antibiotic sensitivity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of RpoN, RpoS and LuxS pathways on the biofilm formation and antibiotIc sensitivity of Borrelia burgdorferi

Sapi¹,

Theophilus²,

Pham³

et al. 2016

EuJMI

Self Cite

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“…The challenge in treating these bacteria has been complicated by several pathophysiological factors, including their ability to remain latent for decades 5, 56-58. The challenge is further exacerbated by findings indicating that Borrelia biofilm may harbor a heterogeneous population of spirochetes and rounded forms with distinct genetic and protein profiles 59-61. In addition, the role of an antibiotic efflux gene needs to be explored 22.…”

Section: Discussionmentioning

confidence: 99%

Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia sp

2016

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Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria.

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“…Recent evidence shedding light on how spirochaetes of the Borrelia genus evade host immune defences and survive antibiotic challenge [10][11][12][13][14][15] threaten current beliefs about the persistence of infection, one of the largest points of contention in the medical community. The possibility of persistent infection has important implications for diagnosis, treatment, and doctor-patient interactions.…”

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confidence: 99%