Disease relevance of bla

• Crystal structure and activity studies of the Mycobacterium tuberculosis beta-lactamase reveal its critical role in resistance to beta-lactam antibiotics [1].
• Identification of Mycobacterium tuberculosis signal sequences that direct the export of a leaderless beta-lactamase gene product in Escherichia coli [2].
• The on-chip amplification was applied to detect the anthrax toxin genes and the plasmid-borne beta-lactamase gene responsible for bacterial ampicillin resistance [3].
• Mycobacteria produce beta-lactamases: M. tuberculosis produces a wide-spectrum beta-lactamase whose behaviour mimicks those of Gram-negative bacteria [4].
• Three classes of drugs show promise for the treatment of drug-resistant tuberculosis: spiropiperidyl rifamycin, the fluoroquinolones, and combinations of beta-lactam agents and beta-lactamase inhibitors [5].

High impact information on bla

• While clavulanate is a mechanism-based inhibitor to class A beta-lactamase with high potency (typically K(i) < 0.1 microM), it is a relatively poor inhibitor of the M. tuberculosis BlaC (K(i) = 2.4 microM) [1].
• However, they are ineffective against Mycobacterium tuberculosis, due to the production of a beta-lactamase enzyme encoded on the chromosome of M. tuberculosis that degrades these antibiotics [1].
• A sequence analysis identified it as a class A beta-lactamase whose expression correlated with the increased resistance phenotype [6].
• The presence of membrane-associated beta-lactamase precluded the use of membranes for assaying the binding affinities of beta-lactam antibiotics [7].
• Resistance could be reversed with the beta-lactamase inhibitors clavulanate or sulbactam or could be circumvented by the use of a beta-lactamase-stable drug, imipenem, indicating that mycobacterial beta-lactamase, probably in conjunction with slow penetration, is a major determinant of M. tuberculosis resistance to beta-lactam antibiotics [7].

Chemical compound and disease context of bla

• Comparison of four beta-lactamase inhibitors in combination with ampicillin against Mycobacterium tuberculosis [8].
• The in-vitro activity of a beta-lactamase inhibitor (clavulanic acid, sulbactam, BL-P2013 or BL-P2090) in combination with ampicillin against 13 isolates of Mycobacterium tuberculosis was determined by broth dilution [8].

Biological context of bla

• We hypothesized that characterizing additional mutants (derived from beta-lactamase deletion mutants) that are hypersusceptible to beta-lactam antibiotics might reveal novel genes involved with other mechanisms of beta-lactam resistance, peptidoglycan assembly, and cell envelope physiology [9].
• Twelve of the beta-lactamase gene fusions conferred high levels of Ampr (up to 1 mg ampicillin ml-1); insert sizes ranged from 350 to 3000 bp [2].
• DESIGN: Cell-associated beta-lactamase was measured by nitrocefin disc method. beta-lactamases obtained from some mycobacteria were studied for their substrate specificity, metal ion-dependency and isoelectric focusing (IEF) patterns [10].

Anatomical context of bla

• Optimum activity was observed at 100 mg/l which killed 58-97% of the mycobacteria within macrophages, as determined by the CFU. beta-Lactam/beta-lactamase-inhibitors, especially ampicillin/sulbactam, might provide an effective alternative therapy against infections caused by mycobacteria resistant to other drugs [11].

Associations of bla with chemical compounds

• The agents were tested in 1:1 molar ratio of ampicillin to beta-lactamase inhibitor [8].
• All isolates were beta-lactamase positive and were resistant to 16 mg/L amoxycillin [12].
• Comparison of the secreted proteins of the deltatatC and parent strain by two-dimensional polyacrylamide gel electrophoresis revealed an alteration in the secretion of at least five proteins, and one of the major TAT-dependent secreted proteins was identified as beta-lactamase (BlaS) [13].
• The combination of clavulanic acid, a beta-lactamase inhibitor, and amoxicillin has been shown bactericidal for M tuberculosis in vitro [14].
• Results using the BACTEC 460 and enzyme activity tests showed the best beta-lactamase inhibitor for M. tuberculosis H37Ra to be clavulanic acid [15].

Analytical, diagnostic and therapeutic context of bla

• Isoelectric focusing detected an M. tuberculosis-derived beta-lactamase in one of these recombinant clones [6].
• Cloning and sequence analysis of a class A beta-lactamase from Mycobacterium tuberculosis H37Ra [6].

References