Biology subjects

Lloyd, V. K.

Publications and source records attributed to Lloyd, V. K..

3 recordsLinked to original sources

bioRxiv2026

Diverse Lyme disease spirochete species evade restriction by human complement

Disseminated human Lyme borreliosis (LB) is traditionally associated with invasive spirochete species from the Borrelia burgdorferi sensu lato (s.l.) complex. The Borrelia burgdorferi sensu lato complex consists of 23 spirochete species worldwide, with additional species being proposed. Interactions between the host immune system and Borrelia species have been studied for a diverse range of vertebrate reservoirs of LB spirochetes, including lizards and snakes, as well as the widely recognized rodent and bird reservoirs. Humans are the vertebrate species most susceptible to B. burgdorferi s.l. spirochetes, as demonstrated by the increasing number of diagnosed LB cases worldwide. However, few studies have evaluated differences in the borreliacidal action of human complement against specific Borrelia species. Using the serum sensitivity test, we analyzed whether complement-mediated killing of 10 spirochete species from the B. burgdorferi s.l. complex varies among healthy human individuals of different ages and sexes. Our results show that the 10 genospecies exhibit varying sensitivities to human complement and can be classified into three statistically distinct groups: high, medium, and low sensitivity. Complement sensitivity did not correlate with the known human health impact of these genospecies; similar resistance to the killing effects of human serum was found among Borrelia species that are major causes of LB worldwide and species with unclear pathogenicity to humans. Additionally, females showed reduced complement-mediated Borrelia killing compared to males for all Borrelia species in almost all age groups. Age and biological sex interacted for the Borrelia species most sensitive to human complement. Overall, the effectiveness of complement-mediated killing of the different Borrelia species tended to decrease with age, with more complex age-dependent changes observed for some Borrelia species.

microbiology↗

bioRxiv2024

Epigenetic responses in Borrelia-infected Ixodes scapularis ticks: Over-expression of euchromatic histone lysine methyltransferase 2 and no change in DNA methylation

Borrelia burgdorferi, a tick-vectored spirochete bacteria best known for causing Lyme disease, has been found to induce physiological and behavioural changes in its tick vector that can increase tick fitness and its ability to transmit the bacteria. The mechanism by which this bacterium modulates these changes remains unknown. Epigenetics plays a central role in transducing external and internal microbiome environmental influences to the organism, so we investigated DNA methylation and the expression of a key histone modification enzyme in Borrelia-infected and uninfected Ixodes scapularis ticks. DNA methylation of the pericentromeric tandem repeats family, Ixodes scapularis Repeats (ISR) were assessed by methylated-DNA immunoprecipitation (MeDIP) followed by qPCR of the ISR regions. DNA methylation of the ISR sequences was found. The different repeats had different levels of DNA methylation, however, these levels were not significantly affected by the presence or absence of B. burgdorferi. The epigenetic regulator euchromatic histone lysine methyltransferase 2 (EHMT2) is recognized as having a key role in modulating the organismal stress response to infections. To assess EHMT2 transcription in Borrelia-infected and uninfected ticks, real-time reverse transcriptase PCR was performed. Uninfected ticks had over 800X lower EHMT2 expression than infected ticks. This study is among the first to identify a gene that may be involved in producing epigenetic differences in ticks depending on infection status and lays the groundwork for future epigenetic studies of I. scapularis in response to B. burgdorferi as well as other pathogens that these ticks transmit.

genetics↗

bioRxiv2022

Changes in the transcriptome and long non-coding RNAs but not the methylome occur in human cells exposed to Borrelia burgdorferi

Lyme disease, caused by infection with members of the Lyme borreliosis group of Borrelia spirochete bacteria, is increasing in frequency and distribution worldwide. This spread is driven by the expansion of ticks, vectors of these pathogens. Epigenetics may be involved in the interaction between mammalian host, tick, and bacterial pathogen, but is still poorly understood. Next-generation sequencing (NGS) allows the study of host response at the transcriptomic and methylomic scale. We tested the effect of the Borrelia burgdorferi strain B31 on a human primary cell line (HUVEC) and an immortalized cell line (HEK-293) for 72 h, a time consistent with the duration of tick feeding and host cell exposure to B. burgdorferi. RNA and DNA were extracted from cells and used for RNA-seq and Enzymatic-Methyl-seq (EM-seq). Differential expression and Reactome pathway enrichment analysis were performed. More significantly differentially expressed genes (a total of 69) were found in HUVECs compared to HEK-293 (a total of 8). Borrelia burgdorferi exposure significantly induced genes in the interferon, cytokine, and other immune response signaling in HUVECs. In HEK-293, pre-NOTCH processing in Golgi was identified as a significant pathway. Other significant genes suggest extracellular matrix binding and interaction in HEK-293. Data comparison with other transcriptomic studies of human cells exposed to B. burgdorferi revealed a small overlap in genes identified in HUVEC, but no overlap for HEK-293. No significant methylation changes were detected in HUVECs or HEK-293 exposed to B. burgdorferi. However, two long non-coding RNAs and a pseudogene were deregulated in response to B. burgdorferi in HUVEC suggesting that other epigenetic mechanisms may be initiated by infection. This is the first study examining the transcriptome and methylome of human cells exposed to B. burgdorferi for 72 h and so contributes to the description of early-stage B. burgdorferi infection at the cellular level.

molecular biology↗