Apparent Role for Borrelia burgdorferi LuxS during Mammalian Infection

Abstract

The Lyme disease spirochete, Borrelia burgdorferi, controls protein expression patterns during its tick-mammal infection cycle. Earlier studies demonstrated that B. burgdorferi synthesizes 4,5-dihydroxy-2,3-pentanedione (autoinducer-2 [AI-2]) and responds to AI-2 by measurably changing production of several infection-associated proteins. luxS mutants, which are unable to produce AI-2, exhibit altered production of several proteins. B. burgdorferi cannot utilize the other product of LuxS, homocysteine, indicating that phenotypes of luxS mutants are not due to the absence of that molecule. Although a previous study found that a luxS mutant was capable of infecting mice, a critical caveat to those results is that bacterial loads were not quantified. To more precisely determine whether LuxS serves a role in mammalian infection, mice were simultaneously inoculated with congenic wild-type and luxS strains, and bacterial numbers were assessed using quantitative PCR. The wild-type bacteria substantially outcompeted the mutants, suggesting that LuxS performs a significant function during mammalian infection. These data also provide further evidence that nonquantitative infection studies do not necessarily provide conclusive results and that regulatory factors may not make all-or-none, black-or-white contributions to infectivity.

Global Tn‐seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi

“…As a large competition assay, the Tn‐seq screen may reveal subtle phenotypes missed in traditional single strain infections. A similar phenomenon in mice has been reported for B. burgdorferi lacking luxS (Arnold et al ., ). For many years, it was thought that luxS mutants were fully infectious (Hubner et al ., ).…”

“…For many years, it was thought that luxS mutants were fully infectious (Hubner et al, 2003). However, an infectivity defect was uncovered in a recent publication in which luxS mutants were out competed by wild-type during mouse infection (Arnold et al, 2015).…”

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

“…One group reported that a luxS-deficient clone of Bb strain 297 retained its infectivity in mice following needle inoculation [232], and also maintained its capacity for tick colonization and transmission [233]. Although the infectivity of the luxS mutant strain was confirmed recently by a quantitative approach that evaluated bacterial burden in tissues, a mixed infection with wildtype and mutant Bb favoured the wildtype cells [234]. This result suggests that LuxS may, indeed, contribute to mammalian colonization, dissemination, and persistence, in ways that are not yet clear.…”

Sleeper cells: the stringent response and persistence in the Borreliella (Borrelia) burgdorferi enzootic cycle

“…2) (Pal et al, 2004;Ferullo and Lovett, 2008;Traxler et al, 2008;Dunham-Ems et al, 2009;2012;Srivastava and de Silva, 2009;Zhang et al, 2011;Meril€ ainen et al, 2015;Gupta et al, 2016). It is plausible that the stringent response mediates these processes since the stringent response in B. burgdorferi (like that in other bacteria) modulates expression of genes of the mevalonate pathway involved in cell wall morphogenesis, inhibition of motility, formation of aggregates and biofilms, and quorum sensing (Potrykus and Cashel, 2008;Dalebroux and Swanson, 2012;Boutte and Crosson, 2013;Arnold et al, 2015;Bugrysheva et al, 2015;Drecktrah et al, 2015;Gupta et al, 2016). After 48 h of feeding, as nutrients from the blood meal begin to be utilized by tick gut epithelial cells and increased nutrients are available to the spirochetes, the stringent response will subside, and spirochetes will begin to divide and rapidly reach high concentrations (Piesman et al, 1990;Dunham-Ems et al, 2009).…”