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.

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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.

Rifampicin (RIF) is one of the most valued drugs in the treatment of tuberculosis. TB treatment relies on a combination therapy and for multidrug-resistant strains may include β-lactams.

Introduction Primary peritonitis (PP) is peritonitis occurring in patients without underlying causes such as perforated viscus, preexisting ascites, or nephrosis. We report 2 cases of primary Streptococcus pyogenes peritonitis and review the literature on this subject since January 1, 2000. Case Reports Patient 1 was a 45-year-old woman who presented to hospital with fever, diarrhea, and abdominal pain. Examination revealed fever, hypotension, epigastric tenderness, and guarding. Computed tomography (CT) scan was negative for signs of perforated viscus. Workup included blood cultures, parenteral antibiotics, and surgical consult. She underwent emergent operative intervention, which revealed generalized peritonitis, cloudy peritoneal fluid, and no evidence of perforated viscus. Blood cultures revealed S. pyogenes. She underwent an unremarkable recovery on parenteral ceftriaxone followed by oral ampicillin. Patient 2 was a 47-year-old woman who presented to hospital with fever, chills, anorexia, nausea, vomiting, and abdominal pain. Physical examination showed fever, hypotension, tachycardia, and diffuse abdominal tenderness but no rebound tenderness. Abdominal CT scan revealed fluid but no free air. Paracentesis revealed purulent fluid, which on Gram-stained smear showed gram-positive cocci in pairs and chains. Blood and peritoneal fluid cultures were positive for S. pyogenes. Exploratory laparotomy by surgical consultant showed purulent fluid and fibrinous exudate with multiple interloop abscesses and no perforated viscus. Postoperatively, she received parenteral penicillin G, transient hemodialysis, and ventilator support with eventual full recovery. Review of Literature We reviewed the medical literature from January 1, 2000, to December 31, 2016, and found 36 patients with diagnosis of S. pyogenes PP. Despite most of these case reports stating that the occurrence of S. pyogenes PP is “rare,” it seems that it is more common than previously thought. All but 3 patients underwent surgical intervention. All 38 patients presented with physical findings of an acute abdomen. There was no evidence of free air on CT scanning or ultrasound of the 33 patients who underwent one of these imaging techniques. Septic shock was common, and all but 1 patient survived. Conclusions Streptococcus pyogenes PP is more common than previously reported, is associated with physical findings of acute abdomen, is usually accompanied by circulatory shock, and is almost always clinically responsive to treatment with operative and antimicrobial agent interventions.

The current study investigates the mycobacterial response towards the combined stress of an organic oxidant (cumene hydroperoxide, CHP) and a solvent (ethanol). To understand the interaction between the two stressors, we treated Mycobacterium smegmatis cells to a range of ethanol concentrations (2.5 – 10 %v/v) in combination with a sub-inhibitory concentration of 1 mM CHP. It was observed that the presence of CHP increases the efficacy of ethanol in inducing rapid cell death. The data further suggests that ethanol reacts with the alkoxy radicals, to produce ethanol-derived peroxides. These radicals induce significant membrane damage leading to cell lysis. The ethanol-derived radicals were primarily recognized by the cells as organic radicals, as was evident by the differential upregulation of the ohrR-ohr genes that function in cells treated with the combination of ethanol and CHP. The role of organic peroxide reductase, Ohr, was further confirmed by the significantly higher sensitivity of the deletion mutant to CHP and the combined stress treatment of CHP and ethanol. Moreover, we also observed the sigma factor σB, to be important for the cells treated with ethanol alone as well as the aforementioned combination. A ΔsigB mutant strain had significantly higher susceptibility towards the stress conditions. This was correlated with the σB-dependent transcriptional regulation of ohr and ohrR. In summary, our data indicates that the combination of low levels of ethanol and organic peroxides, induce ethanol-derived organic radicals that lead to significant oxidative stress on the cells in a concentration-dependent manner. Importance Bacterial response towards a combination of stresses can be unexpected and very different compared to that of an individual stress treatment. This study explores the physiological and transcriptional response of mycobacteria in response to the combinatorial treatment of an oxidant with the commonly used solvent ethanol. Presence of sub-inhibitory concentration of organic peroxide increases the effectiveness of ethanol, by inducing reactive peroxides that destroy the membrane integrity of cells in a significantly short time span. Our work elucidates a mechanism of targeting the complex mycobacterial membrane, which is its primary source of intrinsic resistance. Further, it also demonstrates the importance of exploring the interaction of various stresses conditions on inducing bacterial clearance.