1887

Abstract

The genome contains four highly related genes which present significant similarity to genes encoding phospholipase C enzymes. Three of these genes, , and , are organized in tandem (locus ). The fourth gene, , is located in a different region. This study investigates variations in and genes in clinical isolates of , and ‘’. Genetic polymorphisms were examined by PCR, Southern blot hybridization, sequence analysis and RT-PCR. Seven isolates contain insertions of IS elements within , or . In 19 of 25  isolates examined, genomic deletions were identified, resulting in loss of parts of genes or complete genes from the and/or loci. Partial deletion was observed in one isolate. In each case, deletions were associated with the presence of a copy of the IS element and in all occurrences IS was transposed in the same orientation. A mechanism of deletion resulting from homologous recombination of two copies of IS was recognized in a group of genetically related isolates. Five isolates presented major polymorphisms in the and regions, along with loss of expression competence that affected all four genes. Phospholipase C is a well-known bacterial virulence factor. The precise role of phospholipase C in the pathogenicity of is unknown, but considering the potential importance that the genes may have in the virulence of the tubercle bacillus, the study of isolates cultured from patients with active tuberculosis bearing genetic variations affecting these genes may provide insights into the significance of phospholipase C enzymes for tuberculosis pathogenicity.

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2004-04-01
2024-03-28
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