HtrA, a temperature- and stationary phase-activated protease involved in maturation of a key microbial virulence determinant, facilitates Borrelia burgdorferi infection in mammalian hosts

Meiping Ye, Kavita Sharma, Meghna Thakur, Alexis A. Smith, Ozlem Buyuktanir, Xuwu Xiang, Xiuli Yang, Kamoltip Promnares, Yongliang Lou, X. Frank Yang, Utpal Pal

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2372-2381
Number of pages10
JournalInfection and immunity
Volume84
Issue number8
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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