Bacteria surround themselves with peptidoglycan, an adaptable enclosure that contributes to cell shape and stability. Peptidoglycan assembly relies on penicillin-binding proteins (PBPs) acting in concert with SEDS-family transglycosylases RodA and FtsW, which support cell elongation and division respectively. In Bacillus subtilis, cells lacking all four PBPs with transglycosylase activity (aPBPs) are viable. Here, we show that the alternative sigma factor σI is essential in the absence of aPBPs. Defects in aPBP-dependent wall synthesis are compensated by σI-dependent upregulation of an MreB homolog, MreBH, which localizes the LytE autolysin to the RodA-containing elongasome complex. Suppressor analysis reveals that cells unable to activate this σI stress response acquire gain-of-function mutations in the essential histidine kinase WalK, which also elevates expression of sigI, mreBH and lytE. These results reveal compensatory mechanisms that balance the directional peptidoglycan synthesis arising from the elongasome complex with the more diffusive action of aPBPs.

Bending waves, perturbation modes leading to deflections of the vortex centreline, are considered for an infinitely long straight vortex embedded in an irrotational flow of unlimited extent. We first establish the general form of the dispersion relation for long waves on columnar vortices with arbitrary distributions of axial and azimuthal vorticity by a singular perturbation analysis of the Howard-Gupta equation. The asymptotic results are shown to compare favourably with numerical solutions of the Howard-Gupta equation for wavelengths comparable to the vortex core radius and longer. Dispersion relations are then found numerically for specific models of vortex core structures observed experimentally; here no restrictions are placed on wavelength. The linear dispersion relation has an infinite number of branches, falling into two families; one with infinite phase speed at zero wavenumber (which we call ‘fast’ waves), the other with zero phase speed (‘slow’ waves). In the long-wave limit, slow waves have zero group velocity, while the fast waves may have finite non-zero group speeds that depend on the form of the velocity profiles on the axis of rotation. Weakly nonlinear waves are described under most circumstances by the nonlinear Schrödinger equation. Solitons are possible in certain ‘windows’ of wavenumbers of the carrier waves. An example has already been presented by Leibovich & Ma (1983), who compute solitons and soliton windows on a fast-wave branch for a vortex with a particular core structure. Experimental data of Maxworthy, Hopfinger & Redekopp (1985) reveal solitons which appear to be associated with the slow branch, and these are computed for velocity profiles fitting their data. The nonlinear Schrödinger equation is shown to fail for long waves, and to be replaced by a nonlinear integro-differential equation.

No abstract

Prolonged chemotherapy as well as rapid development of antimicrobial resistance are two of the major concerns for treatment of mycobacterial infections. To enhance the effectiveness of current drug regimens, search for compounds having synergistic interaction with anti-mycobacterial drugs has become indispensable. Here, we have investigated the intervention by oxidative stress, a major factor in mycobacterial pathogenesis, in combination with rifampicin (RIF), a first-line drug used against Mycobacterium tuberculosis. We have observed that a sub-inhibitory concentration of cumene hydroperoxide (CHP), a hydrophobic oxidant, synergistically reduced the minimum inhibitory concentration of RIF by fourfold, with a Fractional Inhibitory Concentration Index (FICI) of 0.45. Also, this interaction was found to be robust and synergistic against different strains of M. smegmatis as well as on M. bovis BCG, with FICI ranging from 0.3 to 0.6. Various physiological, biochemical and molecular parameters were explored to understand the mechanism of synergy. It was observed that increased membrane permeability owing to the presence of the oxidant, led to higher uptake of the drug. Moreover, downregulation of the hydroperoxide reductases by RIF, a transcriptional inhibitor, prevented quenching of the reactive oxygen species produced in the presence of CHP. The lipid soluble reactive species triggered autocatalytic lipid peroxidation (LPO), observed here as extensive membrane damage eventually leading to growth inhibition. Furthermore, it was seen that in combination with hydrogen peroxide (H2O2), the effect was only additive, establishing LPO as a key aspect leading toward synergism. To conclude, this work suggests that targeting the bacterial membrane by a radical species can have a significant impact on the treatment of tuberculosis.

Understanding how a bacterium coordinates cell envelope synthesis is essential to fully appreciate how bacteria grow, divide, and resist cell envelope stresses, such as β-lactam antibiotics. Balanced synthesis of the peptidoglycan cell wall and the cell membrane is critical for cells to maintain shape and turgor pressure and to resist external cell envelope threats.