Advances in the study of New Delhi metallo-β-lactamase 1 / 药学学报

The New Delhi metallo-β-lactamase-1 (NDM-1) was first reported in 2010, detected in a Klebsiella pneumoniae isolate from a Swedish patient of Indian origin. It has recently attracted extensive attention for its biological activities to catalyze the hydrolysis of almost all of β-lactam antibiotics. The gene for NDM-1 can spread from one strain of bacteria to another by horizontal gene transfer. The most troubling aspect is that there are currently no clinically available inhibitors to block the metallo-β-lactamase action. Therefore, there is urgent need to develop new NDM-1 inhibitors, which can protect β-lactam antibiotics from the hydrolysis effect of NDM-1. In this review, the current research, drug-assistant mechanism and potential NDM-1 inhibitors are summarized.

Mechanism of Action of Antimicrobial Peptides Against Bacterial Membrane

Resistance to antibiotics is becoming a very serious problem, with so-called superbugs exhibiting resistance to nearly all conventional antibiotic drugs. Consequently, these organisms often cause severe illness and even death. Alternatives to conventional antibiotics are antimicrobial peptides (AMPs). These widely expressed short peptides, which have been isolated from insects, plants, marine organisms and mammals, including humans, show strong antimicrobial activity against both Gram-negative and Gram-positive bacteria. Most AMPs act by disrupting the bacterial membrane through "Barrel-stave", "Toroidal pore", "carpet" mechanism. In addition, AMPs may prevent septic shock through strongly binding lipopolysaccharides and lipoteichoic acid located on the bacterial membrane. The action mechanisms of AMP to minimize the likelihood developing resistance to the peptides would be particular advantage. For these reasons, we anticipate that AMPs will replace conventional antibiotic drugs in a variety of contexts.

NDM-1 Resistance: Fleming’s predictions become true.

Bacteria, beside other microorganisms are mainly responsible for human sufferings beside their beneficial effects. After discovery of Penicillin bacterial diseases were controlled to a much extent. The name ‘antibiotic’ makes us feel that we, humans are superior at least from microorganisms. Serious infections caused by bacteria that have become resistant to commonly used antibiotics have become a major global healthcare problem in the 21st century. Resistance to antibiotics shows that they can fight back and challenge our knowledge and intellect. Discovery of New Delhi metallo-1 make us feel that this is the result of our own ignorance. Indiscriminate, irrational and illogical use of antibiotics is helping bacteria to fight against us. What objections are being raised at the Govt. level, and how research community defends us, keeping that apart, the question is to realize and resolve the threat rather than to overlook it. Our outlook need to be changed and health policies and guidelines need to be reevaluated and overhauled timely.