Dataset Information

HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts.

ABSTRACT: High-temperature requirement protease A (HtrA) represents a family of serine proteases that play important roles in microbial biology. Unlike the genomes of most organisms, that of Borrelia burgdorferi notably encodes a single HtrA gene product, termed BbHtrA. Previous studies identified a few substrates of BbHtrA; however, their physiological relevance could not be ascertained, as targeted deletion of the gene has not been successful. Here we show that BbhtrA transcripts are induced during spirochete growth either in the stationary phase or at elevated temperature. Successful generation of a BbhtrA deletion mutant and restoration by genetic complementation suggest a nonessential role for this protease in microbial viability; however, its remarkable growth, morphological, and structural defects during cultivation at 37°C confirm a high-temperature requirement for protease activation and function. The BbhtrA-deficient spirochetes were unable to establish infection of mice, as evidenced by assessment of culture, PCR, and serology. We show that transcript abundance as well as proteolytic processing of a borrelial protein required for cell fission and infectivity, BB0323, is impaired in BbhtrA mutants grown at 37°C, which likely contributed to their inability to survive in a mammalian host. Together, these results demonstrate the physiological relevance of a unique temperature-regulated borrelial protease, BbHtrA, which further enlightens our knowledge of intriguing aspects of spirochete biology and infectivity.

SUBMITTER: Ye M

PROVIDER: S-EPMC4962642 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts.

Ye Meiping M Sharma Kavita K Thakur Meghna M Smith Alexis A AA Buyuktanir Ozlem O Xiang Xuwu X Yang Xiuli X Promnares Kamoltip K Lou Yongliang Y Yang X Frank XF Pal Utpal U

Infection and immunity 20160721 8

High-temperature requirement protease A (HtrA) represents a family of serine proteases that play important roles in microbial biology. Unlike the genomes of most organisms, that of Borrelia burgdorferi notably encodes a single HtrA gene product, termed BbHtrA. Previous studies identified a few substrates of BbHtrA; however, their physiological relevance could not be ascertained, as targeted deletion of the gene has not been successful. Here we show that BbhtrA transcripts are induced during spir ...[more]

PMID: 27271745

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Project description:Lyme disease and human babesiosis are the most common tick-borne zoonoses in the Temperate Zone of North America. The number of infected patients has continued to rise globally, and these zoonoses pose a major healthcare threat. This tick-host-pathogen study was conducted to test for infectious microbes associated with Lyme disease and human babesiosis in Canada. Using the flagellin (flaB) gene, three members of the Borrelia burgdorferi sensu lato (Bbsl) complex were detected, namely a Borrelia lanei-like spirochete, Borrelia burgdorferi sensu stricto (Bbss), and a distinct strain that may represent a separate Bbsl genospecies. This novel Bbsl strain was detected in a mouse tick, Ixodes muris, collected from a House Wren, Troglodytes aedon, in Quebec during the southward fall migration. The presence of Bbsl in bird-feeding larvae of I. muris suggests reservoir competency in three passerines (i.e., Common Yellowthroat, House Wren, Magnolia Warbler). Based on the 18S ribosomal RNA (rRNA) gene, three Babesia species (i.e., Babesia divergens-like, Babesia microti, Babesia odocoilei) were detected in field-collected ticks. Not only was B. odocoilei found in songbird-derived ticks, this piroplasm was apparent in adult questing blacklegged ticks, Ixodes scapularis, in southern Canada. By allowing live, engorged ticks to molt, we confirm the transstadial passage of Bbsl in I. muris and B. odocoilei in I. scapularis. Bbss and Babesia microti were detected concurrently in a groundhog tick, Ixodes cookei, in Western Ontario. In Alberta, a winter tick, Dermacentor albipictus, which was collected from a moose, Alces alces, tested positive for Bbss. Notably, a B. divergens-like piroplasm was detected in a rabbit tick, Haemaphysalis leporispalustris, collected from an eastern cottontail in southern Manitoba; this Babesia species is a first-time discovery in Canada. This rabbit tick was also co-infected with Borrelia lanei-like spirochetes, which constitutes a first in Canada. Overall, five ticks were concurrently infected with Babesia and Bbsl pathogens and, after the molt, could potentially co-infect humans. Notably, we provide the first authentic report of I. scapularis ticks co-infected with Bbsl and B. odocoilei in Canada. The full extent of infectious microorganisms transmitted to humans by ticks is not fully elucidated, and clinicians need to be aware of the complexity of these tick-transmitted enzootic agents on human health. Diagnosis and treatment must be administered by those with accredited medical training in tick-borne zoonosis.

Dataset Information

HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts.

Publications

HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts.

Similar Datasets

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