Browsing by Author "Du, Jimei"

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    Corrigendum: Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi
    (Frontiers Media, 2021-03-31) Liu, Qiang; Xu, Haijun; Zhang, Yan; Yang, Jing; Du, Jimei; Zhou, Yan; Yang, X. Frank; Lou, Yongliang; Microbiology and Immunology, School of Medicine
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    Investigation of ospC Expression Variation among Borrelia burgdorferi Strains
    (Frontiers, 2017-04-20) Xiang, Xuwu; Yang, Youyun; Du, Jimei; Lin, Tianyu; Chen, Tong; Yang, X. Frank; Lou, Yongliang; Microbiology and Immunology, School of Medicine
    Outer surface protein C (OspC) is the most studied major virulence factor of Borrelia burgdorferi, the causative agent of Lyme disease. The level of OspC varies dramatically among B. burgdorferi strains when cultured in vitro, but little is known about what causes such variation. It has been proposed that the difference in endogenous plasmid contents among strains contribute to variation in OspC phenotype, as B. burgdorferi contains more than 21 endogenous linear (lp) and circular plasmids (cp), and some of which are prone to be lost. In this study, we analyzed several clones isolated from B. burgdorferi strain 297, one of the most commonly used strains for studying ospC expression. By taking advantage of recently published plasmid sequence of strain 297, we developed a multiplex PCR method specifically for rapid plasmid profiling of B. burgdorferi strain 297. We found that some commonly used 297 clones that were thought having a complete plasmid profile, actually lacked some endogenous plasmids. Importantly, the result showed that the difference in plasmid profiles did not contribute to the ospC expression variation among the clones. Furthermore, we found that B. burgdorferi clones expressed different levels of BosR, which in turn led to different levels of RpoS and subsequently, resulted in OspC level variation among B. burgdorferi strains.
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    Positive and Negative Regulation of Glycerol Utilization by the c-di-GMP Binding Protein PlzA in Borrelia burgdorferi
    (American Society for Microbiology, 2018-10-23) Zhang, Jun-Jie; Chen, Tong; Yang, Youyun; Du, Jimei; Li, Hongxia; Troxell, Bryan; He, Ming; Carrasco, Sebastian E.; Gomelsky, Mark; Yang, X. Frank; Microbiology and Immunology, School of Medicine
    Borrelia burgdorferi, the causative agent of Lyme disease, encounters two disparate host environments during its enzootic life cycle, Ixodes ticks and mammalian hosts. B. burgdorferi has a small genome that encodes a streamlined cyclic dimeric GMP (c-di-GMP) signaling system comprising a single diguanylate cyclase, Rrp1, and two phosphodiesterases. This system is essential for spirochete survival in ticks, in part because it controls the expression of the glp operon involved in glycerol utilization. In this study, we showed that a B. burgdorferi c-di-GMP receptor, PlzA, functions as both a positive and a negative regulator for glp expression. Deletion of plzA or mutation in plzA that impaired c-di-GMP binding abolished glp expression. On the other hand, overexpression of plzA resulted in glp repression, which could be rescued by simultaneous overexpression of rrp1. plzA overexpression in the rrp1 mutant, which is devoid of c-di-GMP, or overexpression of a plzA mutant incapable of c-di-GMP binding further enhanced glp repression. Combined results suggest that c-di-GMP-bound PlzA functions as a positive regulator, whereas ligand-free PlzA acts as a negative regulator for glp expression. Thus, PlzA of B. burgdorferi with a streamlined c-di-GMP signaling system not only controls multiple targets, as previously envisioned, but has also evolved different modes of action.IMPORTANCE The Lyme disease pathogen, Borrelia burgdorferi, has a simple cyclic dimeric GMP (c-di-GMP) signaling system essential for adaptation of the pathogen to the complicated tick environment. The c-di-GMP effector of B. burgdorferi, PlzA, has been shown to regulate multiple cellular processes, including motility, osmolality sensing, and nutrient utilization. The findings of this study demonstrate that PlzA not only controls multiple targets but also has different functional modalities, allowing it to act as both positive and negative regulator of the glp operon expression. This work highlights how bacteria with a small genome can compensate for the limited regulatory repertoire by increasing the complexity of targets and modes of action in their regulatory proteins.
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    Role of HK2 in the Enzootic Cycle of Borrelia burgdorferi
    (Frontiers, 2020-10-26) Liu, Qiang; Xu, Haijun; Zhang, Yan; Yang, Jing; Du, Jimei; Zhou, Yan; Yang, X. Frank; Lou, Yongliang; Microbiology and Immunology, School of Medicine
    The two-component response regulator Rrp2 is a key activator controlling the production of numerous virulence factors of Borrelia burgdorferi, the Lyme disease pathogen. Previously it was shown that the cognate histidine kinase HK2 is not required for Rrp2 activation in vitro, nor for mammalian infection upon needle inoculation, raising the question whether HK2 has any role in the enzootic cycle of B. burgdorferi. In this study, we demonstrated that HK2 is not required for spirochetal survival in the tick vector. When fed on naive mice, the hk2 mutant had reduced infectivity through the route of tick bite, suggesting that the spirochetes lacking HK2 had a disadvantage in the enzootic cycle. Furthermore, overexpression of hk2 reduced the level of Rrp2 phosphorylation, suggesting that HK2 can function as a phosphatase to dephosphorylate Rrp2. Strains overexpressing hk2 impaired the expression of RpoN regulon whose activation is dependent on Rrp2 phosphorylation and activation, and had reduced infectivity in mice. Taken together, these results demonstrate that although HK2 does not play an essential role in Rrp2 activation, it is important for the optimal fitness of B. burgdorferi in the enzootic cycle.