Summary auto-generated
This study identified and characterized a cytolethal toxin (CLT) produced by Burkholderia pseudomallei, the bacterium causing melioidosis, a potentially fatal disease endemic in Southeast Asia and northern Australia. Researchers isolated CLT from culture filtrates of various bacterial strains obtained from soil, animals, and infected patients. CLT is a small peptide (~3 kDa) that kills cultured McCoy cells within 1-12 hours by causing cell rounding, membrane distortion, and rapid inhibition of DNA and protein synthesis. The toxin is active at very low concentrations. Notably, CLT production varied significantly among isolates: soil samples were low producers, while strains from patients with melioidosis encephalitis were high producers, suggesting toxin production is regulated. Interestingly, the same bacterial strain showed high toxin production when isolated from an infected goat but low production when isolated from soil, demonstrating environmental regulation of virulence. The study also identified a second toxic activity—a cell-elongating factor (CEA)—that appears to be a protein causing cell elongation and growth inhibition. These findings suggest CLT may contribute to the rapid onset and severity of septicemic melioidosis.
Key findings
- CLT is a small peptide toxin (~3 kDa) produced by B. pseudomallei that rapidly kills cultured cells by inhibiting macromolecular synthesis and causing membrane disruption
- Toxin production varies dramatically among isolates: soil isolates are low producers while strains from encephalitis patients are high producers, suggesting clinical severity correlates with CLT levels
- The same bacterial strain produces different toxin levels depending on source (high from infected animals, low from soil), indicating CLT production is regulated by environmental or host factors
- B. pseudomallei produces two distinct toxic activities: CLT (small peptide, cytolethal) and CEA (protein, causes cell elongation), which are separable by ultrafiltration
- CLT is a candidate virulence factor for the rapid onset of septicemic melioidosis and represents a potential therapeutic target
This summary was generated automatically from the article PDF and is not part of the original publication. Refer to the PDF for the authoritative text.
Abstract
An exotoxin lethal to cells in culture (cytolethal toxin, CLT) was identified in culture filtrates of Burkholderia pseudomallei, the causative organism of melioidosis. CLT could pass through a 10-kDa cut-off ultrafilter and its properties suggest that it is a peptide. Isolates from soil, animals and man showed differential cytolethality in vitro. The isolates were divided into low, medium and high CLT producers with soil isolates being low producers and isolates from patients with melioidosis encephalitis being high producers. CLT levels are subject to regulation, as a strain isolated from an infected goat was one of the highest producers whereas the same strain isolated from soil was a low producer. In addition to CLT, all isolates produced a protein with cell-elongating activity which was also present in culture filtrates.