Virulence of Mycobacterium tuberculosis

Abstract Different strains of Candida albicans show varied sensitivities to the peptide analogues bacilysin, polyoxins and nikkomycins. From a sensitive strain, B2630, spontaneous mutants were selected for resistance to each analogue; certain mutants showed cross-resistance to other analogues and associated defects in peptide transport. A bacilysin-resistant mutant was cross resistant to the other analogues and to m -fluorophenylalanyl-Ala (FPA) but retained sensitivity to m -fluorophenylalanyl-Ala—Ala (FPAA). It showed defective dipeptide transport but normal oligopeptide transport. A revertant, selected for its ability to utilize Ala-Ala as sole nitrogen source, regained wild-type dipeptide transport activity and analogue sensitivity. Thus, C. albicans has distinguishable mechanisms for dipeptide and oligopeptide transport which can be exploited for uptake of peptide-drug adducts.     

The rpsL gene and streptomycin resistance in single and multiple drug-resistant strains of Mycobacterium tuberculosis

The recent emergence of indolent and rapidly fatal drug-resistant strains of Mycobacterium tuberculosis has renewed interest in defining the molecular mechanisms of drug resistance in the tubercle bacilli. In this report, we have examined the mechanism of resistance to streptomycin (Sm) in M. tuberculosis through the cloning and nucleotide sequence analysis of the gene encoding the ribosomal S^R protein (rpsL gene) from streptomycin-resistant strains and their streptomycin-sensitive parental strains. We have demonstrated that five singly Sm^RM. tuberculosis strains and an Sm^R isolate that has reduced sensitivity to multiple antibiotics have identical point mutations at codon 43 of the rpsL gene. Mutations at this same site confer Sm^R in Escherichia coli. In contrast, two other multiple drug-resistant M. tuberculosis strains that are resistant to Sm have rpsL genes that have the same nucleotide sequence as their drug-sensitive parent strains, suggesting that different resistance mechanisms are involved in these strains.     

Virulence of Mycobacterium tuberculosis and susceptibility to peroxidative killing systems.

At sub-bactericidal concentrations of hydrogen peroxide, Mycobacterium tuberculosis was killed by hydrogen peroxide/peroxidase/halide microbicidal systems. The halide cofactor could be either iodide or, with much lower efficiency, chloride. Omission of any one of the reactants eliminated the tuberculocidal effect. Differences in susceptibility between different strains of M. tuberculosis did not correlate with virulence differences. The observations are discussed in the context of host defence mechanisms against tuberculosis.     

Virulence genotypes of Escherichia coli strains from bacteremia in relation to phylogeny

Bacteremia is the principal way of dissemination of local infections to distant organs. Escherichia coli bacteremia is almost always clinically significant, suggesting an increased risk of developing sepsis syndrome. Fifty-one E. coli bloodstream human isolates were analyzed using PCR technique for several molecular markers associated with extraintestinal virulence, and their phylogenetic group assignment, taking into account the link between the phylogenetic background and the intrinsic virulence of this species. Sixteen virulence genotypes have been identified, the majority of the blood isolates carrying the association of two genes. The genes encoding type 1 fimbria and aerobactin had the highest prevalence. As a confirmation of other studies, the strains assigned to E. coli phylogenetic group B2 exhibited the highest concentration of virulence genes, and represented almost half of the clinical blood isolates. The multifactorial virulence of E. coli strains isolated from invasive infections reflects a phylogenetic inheritance, and supports the concept of ExPEC pathotype as a subset of E. coli population involved in human infectious diseases. The surveillance of geographical variation of E. coli pathogenic clones is useful for epidemiological analysis.     

Mycobacterium tuberculosis strains possess functional cellulases

The genomes of various Mycobacterium tuberculosis strains encode proteins that do not appear to play a role in the growth or survival of the bacterium in its mammalian host, including some implicated in plant cell wall breakdown. Here we show that M. tuberculosis H37Rv does indeed possess a functional cellulase. The x-ray crystal structure of this enzyme, in ligand complex forms, from 1.9 to 1.1A resolution, reveals a highly conserved substrate-binding cleft, which affords similar, and unusual, distortion of the substrate at the catalytic center. The endoglucanase activity, together with the existence of a putative membrane-associated crystalline polysaccharide-binding protein, may reflect the ancestral soil origin of the Mycobacterium or hint at a previously unconsidered environmental niche.