The directed evolution of NDM-1.

ß-Lactam antibiotics are among the most frequently prescribed therapeutic agents. A common mechanism of resistance toward ß-lactam antibiotics is the production of ß-lactamases. These enzymes are capable of hydrolyzing the ß-lactam bond, rendering the drug inactive. Among the four described classes, the metallo- ß-lactamases (MBLs, class B) employ one or two zinc ions in the active site for catalysis. One of the three most clinically relevant MBLs is New Delhi Metallo- ß-Lactamase (NDM-1). The current study sought to investigate the in vitro protein evolution of NDM-1 ß-lactamase using error-prone polymerase chain reaction. Evaluation revealed that variants were not found to confer higher levels of resistance toward meropenem based on amino acid substitutions. Thus, we postulate that increases in transcription or changes in zinc transport may be clinically more relevant to meropenem resistance than amino acid substitutions.

Bellini duct carcinoma of the kidney masquerading as an iliac bone tumour in an adult Nigerian.

Bellini Duct Carcinoma (BDC) of the Kidney is a rare type of Renal Cell Carcinoma. It usually presents with features of local advancement or metastasis and rarely diagnosed incidentally. We present a case report of a young man who was found to have BDC of the Right Kidney following presentation with an iliac bone tumour. A 40 year old man presented to the Orthopaedic outpatient clinic on account of right sided pelvic pain and limping following a trivial fall at home. There was no antecedent history of loin pain, loin mass or haematuria. On evaluation, he was found to have a huge right iliac bone tumour invading the contiguous muscles. An incidental hypodense central ipsilateral renal mass with enlarged peri-hilar lymph nodes were found. He subsequently had right radical nephrectomy via a right sub-coastal approach and wide local excision of the Iliac bone tumour in two separate procedures. The resection margins were negative for tumour cells. Histology of the resected specimens were consistent with a metastatic right BDC of the kidney. He had a smooth post-operative recovery. One third of BDC of the kidney presents with metastasis. A high index of suspicion is required in order to diagnose BDC following such unusual presentations.