Characterization of Clostridium perfringens TpeL Toxin Gene Carriage, Production, Cytotoxic Contributions, and Trypsin Sensitivity

Abstract

Large clostridial toxins (LCTs) are produced by at least four pathogenic clostridial species, and several LCTs are proven pivotal virulence factors for both human and veterinary diseases. TpeL is a recently identified LCT produced by Clostridium perfringens that has received relatively limited study. In response, the current study surveyed carriage of the tpeL gene among different C. perfringens strains, detecting this toxin gene in some type A, B, and C strains but not in any type D or E strains. This study also determined that all tested strains maximally produce, and extracellularly release, TpeL at the late-log or early-stationary growth stage during in vitro culture, which is different from the maximal late-stationary-phase production reported previously for other LCTs and for TpeL production by C. perfringens strain JIR12688. In addition, the present study found that TpeL levels in culture supernatants can be repressed by either glucose or sucrose. It was also shown that, at natural production levels, TpeL is a significant contributor to the cytotoxic activity of supernatants from cultures of tpeL-positive strain CN3685. Lastly, this study identified TpeL, which presumably is produced in the intestines during diseases caused by TpeL-positive type B and C strains, as a toxin whose cytotoxicity decreases after treatment with trypsin; this finding may have pathophysiologic relevance by suggesting that, like beta toxin, TpeL contributes to type B and C infections in hosts with decreased trypsin levels due to disease, diet, or age.

Clostridium perfringens Sporulation and Sporulation-Associated Toxin Production

“…While the above evidence supports tpe L expression during sporulation, TpeL production by C. perfringens isolates during vegetative growth has also been reported (98, 99). Furthermore, those studies found repression of TpeL production mediated by glucose in a similar manner to LCT production by C. difficile .…”

NanI Sialidase, CcpA, and CodY Work Together To Regulate Epsilon Toxin Production by Clostridium perfringens Type D Strain CN3718

“…However, previous studies (37,(40)(41)(42) have shown that mutations from group II introns inserted in the sense orientation can be partially reversed at the mRNA level by growth at 30°C in the presence of an LtrA-encoding plasmid, such as pJIR750ccpAi, with the frequency of this reversion varying for different intron insertions. Therefore, pJIR750ccpAi was reintroduced into strain ccpAko, creating strain ccpArev, in order for LtrA to remove by splicing under permissive 30°C conditions, the sense-oriented intron from some ccpA mRNA, thus restoring a functional ccpA transcript and CcpA production.…”

Role of Clostridium perfringens Toxins in Necrotic Enteritis in Poultry

“…A large clostridial glucosylating cytotoxin referred to as TpeL, and homologous to TcdA and TcdB from C. difficile, also appears to have a role in the pathogenesis of NE (Chen and McClane 2015). TpeL is encoded on a conjugative plasmid (Chen and McClane 2015) and binds to LDL receptor-related protein 1 in the target cells (Schorch et al 2014).…”

“…A large clostridial glucosylating cytotoxin referred to as TpeL, and homologous to TcdA and TcdB from C. difficile, also appears to have a role in the pathogenesis of NE (Chen and McClane 2015). TpeL is encoded on a conjugative plasmid (Chen and McClane 2015) and binds to LDL receptor-related protein 1 in the target cells (Schorch et al 2014). Experimental infections with C. perfringens TpeL-positive strains in broilers induce more severe intestinal lesions and cause NE, with a more rapid course and higher fatality rate than those strains lacking this cytotoxin (Coursodon et al 2012).…”