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The emergence of resistance to antibacterial agents is a pressing concern for human health. New drugs to combat this problem are therefore in great demand, but as past experience indicates, the time for resistance to new drugs to develop is often short. Conventionally, antibacterial drugs have been developed on the basis of their ability to inhibit(More)
In order to determine which genes are involved in maintaining viability of 100-day stationary-phase bacteria and persistent bacteria after antibiotic treatment, we used a mini-DNA array to examine the transcription of 82 genes of M. tuberculosis in the 100-day stationary-phase cultures before and after rifampicin treatment. We found that the mRNA level of a(More)
BACKGROUND The Whitehall cohort studies (I and II) of British civil servants have identified sociodemographic, psychosocial, and biological risk factors for coronary heart disease (CHD). To identify mechanisms responsible for susceptibility to CHD, specific biological markers of stress are increasingly being measured. One marker linked to susceptibility to(More)
The bactericidal activities of ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, and gatifloxacin were tested in three models of rifampin-tolerant Mycobacterium tuberculosis persisters. Model 1 was a 100-day-old, unshaken, anaerobically adapted culture in which serial dilutions of the quinolones were incubated for 5 days and CFU counts were then done In(More)
SETTING Experiments in vitro on the bactericidal activity of metronidazole and in the Cornell model of murine tuberculosis. OBJECTIVE To assess the sterilising activity of maximal metronidazole dosage and its activity against bacilli held dormant by immunity in the mouse. DESIGN In vitro experiments showed that metronidazole was only bactericidal at(More)
Heat-shock protein (hsp)60/chaperonin 60 is a potent immunogen which has recently been claimed to have cell-signalling actions upon myeloid and vascular endothelial cells. The literature is controversial with different chaperonin 60 proteins producing different patterns of cellular activation and the ever-present criticism that activity is the result of(More)
A 65-kDa protein and a 10-kDa protein are two of the more strongly immunoreactive components of Mycobacterium tuberculosis, the causative agent of tuberculosis. The 65-kDa antigen has homology with members of the GroEL or chaperonin-60 (Cpn60) family of heat shock proteins. The 10-kDa antigen has homology with the GroES or chaperonin-10 family of heat shock(More)
The 16-kDa protein, an alpha-crystallin homologue, is one of the most abundant proteins in stationary-phase Mycobacterium tuberculosis. Here, transcription and translation of the hspX gene, which encodes the 16-kDa protein, have been investigated by Northern blotting analysis, primer extension, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis(More)
The cell biology of the chaperonins (Cpns) has been intensively studied over the past 25 years. These ubiquitous and essential molecules assist proteins to fold into their native state and function to protect proteins from denaturation after stress. The structure of the most widely studied Cpn60, Escherichia coli GroEL, has been solved and its mechanism of(More)
The causative agent of tuberculosis, Mycobacterium tuberculosis, has two chaperonin (Cpn60) proteins and one cochaperonin (Cpn10) protein. We show here that cpn60.2 and cpn10, but not cpn60.1, are essential for cell survival. A mutant lacking Cpn60.1 was indistinguishable from the wild-type organism in plate and broth culture and within murine macrophages,(More)