dWhile ␤-lactam antibiotics are a critical part of the antimicrobial arsenal, they are frequently compromised by various resistance mechanisms, including changes in penicillin binding proteins of the bacterial cell wall. Genetic deletion of the penicillin binding protein and serine/threonine kinase-associated protein (PASTA) kinase in methicillin-resistant Staphylococcus aureus (MRSA) has been shown to restore ␤-lactam susceptibility. However, the mechanism remains unclear, and whether pharmacologic inhibition would have the same effect is unknown. In this study, we found that deletion or pharmacologic inhibition of the PASTA kinase in Listeria monocytogenes by the nonselective kinase inhibitor staurosporine results in enhanced susceptibility to both aminopenicillin and cephalosporin antibiotics. Resistance to vancomycin, another class of cell wall synthesis inhibitors, or antibiotics that inhibit protein synthesis was unaffected by staurosporine treatment. Phosphorylation assays with purified kinases revealed that staurosporine selectively inhibited the PASTA kinase of L. monocytogenes (PrkA). Importantly, staurosporine did not inhibit a L. monocytogenes kinase without a PASTA domain (Lmo0618) or the PASTA kinase from MRSA (Stk1). Finally, inhibition of PrkA with a more selective kinase inhibitor, AZD5438, similarly led to sensitization of L. monocytogenes to ␤-lactam antibiotics. Overall, these results suggest that pharmacologic targeting of PASTA kinases can increase the efficacy of ␤-lactam antibiotics.

Background: Laparoscopic cholecystectomy is commonly performed, and several factors increase the

A 32 year old man presented to casualty on three occasions in the space of four days, with intermittent, worsening abdominal pain. These symptoms imitated other commoner causes of acute abdomen and the site of onset changed, both factors delaying diagnosis. In due course, computer tomography imaging established findings indicative of omental infarction. Patient was discharged from hospital nine days later, having made a satisfactory recovery following successful conservative treatment. In this report, we evaluate the merits of a similar approach in future instances.

Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics.

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