Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis?

Potentiation of Available Antibiotics by Targeting Resistance – An Emerging Trend in Tuberculosis Drug Development

“…Furthermore, studies using mouse peritoneal macrophages infected with M. tuberculosis indicated that penetration through neither host macrophage nor phagosomal membranes appears to be a problem for lactams and/or lactamase inhibitors (Chambers et al, 1995, Prabhakaran et al, 1999. Significant reduction of mycobacterial counts in mouse macrophages upon treatment with various combinations of lactams and lactamase inhibitors within clinically achievable doses has been demonstrated (Chambers et al, 1995, Prabhakaran et al, 1999.…”

“…Penetration by diffusion of lactams through the mycobacterial cell wall is hundreds of times slower than that of Escherichia coli (Chambers et al, 1995, Kasik & Peacham, 1968. However, because of the extremely long generation time of M. tuberculosis, the slow rate of drug penetration is enough to allow for half-equilibration over the membrane well before the cell divides, making cell wall permeability and therefore drug penetration important but not a major determinant of lactam resistance (Chambers et al, 1995, Quinting et al, 1997. As for drug target affinity, four major PBPs have been identified in M. tuberculosis, all of which bind lactams at therapeutically achievable concentrations (Chambers et al, 1995).…”

“…On top of these aforementioned layers is another layer consisting of mycolic acids linked to acyl lipids, which forms a waxy, nonfluid barrier restricting transport of both hydrophobic and hydrophilic molecules (Liu et al, 1995). Penetration by diffusion of lactams through the mycobacterial cell wall is hundreds of times slower than that of Escherichia coli (Chambers et al, 1995, Kasik & Peacham, 1968. However, because of the extremely long generation time of M. tuberculosis, the slow rate of drug penetration is enough to allow for half-equilibration over the membrane well before the cell divides, making cell wall permeability and therefore drug penetration important but not a major determinant of lactam resistance (Chambers et al, 1995, Quinting et al, 1997.…”

“…However, because of the extremely long generation time of M. tuberculosis, the slow rate of drug penetration is enough to allow for half-equilibration over the membrane well before the cell divides, making cell wall permeability and therefore drug penetration important but not a major determinant of lactam resistance (Chambers et al, 1995, Quinting et al, 1997. As for drug target affinity, four major PBPs have been identified in M. tuberculosis, all of which bind lactams at therapeutically achievable concentrations (Chambers et al, 1995). The 49-kDa PBP from M. smegmatis is also sensitive to several lactams at similar concentrations (Mukherjee et al, 1996).…”

“…In the case of mycobacteria, resistance to lactams involves three main components: permeability of the mycobacterial cell wall (Chambers et al, 1995, Jarlier et al, 1991, Jarlier & Nikaido, 1990, Kasik & Peacham, 1968, affinity of the drugs to their target PBPs (Chambers et al, 1995, Mukherjee et al, 1996, and degradation by lactamase activity (Jarlier et al, 1991, Quinting et al, 1997. In addition, since M. tuberculosis is an intracellular pathogen, an effective TB drug must be able to penetrate the macrophage and phagosomal membranes to reach the bacilli residing within.…”