The oligopeptide ABC transporter OppA4 negatively regulates the virulence factor OspC production of the Lyme disease pathogen

Bibi Zhou, Youyun Yang, Tong Chen, Yongliang Lou, X. Yang

Research output: Contribution to journalArticle

Abstract

Borrelia burgdorferi sensu lato, the agent of Lyme disease, exists in nature through a complex enzootic life cycle that involves both ticks and mammals. The B. burgdorferi genome encodes five Oligopeptide ABC transporters (Opp) that are predicted to be involve in transport of various nutrients. Previously, it was reported that OppA5 is important for the optimal production of OspC, a major virulence factor of B. burgdorferi. In this study, possible role of another Oligopeptide ABC transporter, OppA4 in ospC expression was investigated by construction of an oppA4 deletion mutant and the complemented strain. Inactivation of oppA4 resulted an increased production of OspC, suggesting that OppA4 has a negative impact on ospC expression. Expression of ospC is controlled by Rrp2-RpoN-RpoS, the central pathway essential for mammal infection. We showed that increased ospC expression in the oppA4 mutant was due to an increased rpoS expression. We then further investigated how OppA4 negatively regulates this pathway. Two regulators, BosR and BadR, are known to positively and negatively, respectively, regulate the Rrp2-RpoN-RpoS pathway. We found that deletion of oppA4 resulted in an increased level of BosR. Previous reports showed that bosR is mainly regulated at the post-transcriptional level by other factors. However, OppA4 appears to negatively regulate bosR expression at the transcriptional level. The finding of OppA4 involved in regulation of the Rrp2-RpoN-RpoS pathway further reinforces the importance of nutritional virulence to the enzootic cycle of B. burgdorferi.

Original languageEnglish (US)
JournalTicks and Tick-borne Diseases
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

oligopeptides
Oligopeptides
Borrelia burgdorferi
ABC transporters
ATP-Binding Cassette Transporters
Lyme disease
Lyme Disease
production economics
Virulence Factors
Mammals
virulence
Borrelia burgdorferi Group
pathogens
Ticks
Life Cycle Stages
Virulence
Genome
mammals
Food
mutants

Keywords

  • Borrelia burgdorferi
  • OppA4
  • OspC

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Insect Science
  • Infectious Diseases

Cite this

The oligopeptide ABC transporter OppA4 negatively regulates the virulence factor OspC production of the Lyme disease pathogen. / Zhou, Bibi; Yang, Youyun; Chen, Tong; Lou, Yongliang; Yang, X.

In: Ticks and Tick-borne Diseases, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "Borrelia burgdorferi sensu lato, the agent of Lyme disease, exists in nature through a complex enzootic life cycle that involves both ticks and mammals. The B. burgdorferi genome encodes five Oligopeptide ABC transporters (Opp) that are predicted to be involve in transport of various nutrients. Previously, it was reported that OppA5 is important for the optimal production of OspC, a major virulence factor of B. burgdorferi. In this study, possible role of another Oligopeptide ABC transporter, OppA4 in ospC expression was investigated by construction of an oppA4 deletion mutant and the complemented strain. Inactivation of oppA4 resulted an increased production of OspC, suggesting that OppA4 has a negative impact on ospC expression. Expression of ospC is controlled by Rrp2-RpoN-RpoS, the central pathway essential for mammal infection. We showed that increased ospC expression in the oppA4 mutant was due to an increased rpoS expression. We then further investigated how OppA4 negatively regulates this pathway. Two regulators, BosR and BadR, are known to positively and negatively, respectively, regulate the Rrp2-RpoN-RpoS pathway. We found that deletion of oppA4 resulted in an increased level of BosR. Previous reports showed that bosR is mainly regulated at the post-transcriptional level by other factors. However, OppA4 appears to negatively regulate bosR expression at the transcriptional level. The finding of OppA4 involved in regulation of the Rrp2-RpoN-RpoS pathway further reinforces the importance of nutritional virulence to the enzootic cycle of B. burgdorferi.",
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