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AMP – the New Weapon to Fight Infection
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2012-04-28

Infection is one of the major causes of patients’ death. According to a recent survey, only in US, the annual incidence of septicemia is 750000 cases, and among them, 225000 cases will end in death. Nowadays, the antibiotics market value has rocketed to over $30 billion, but unfortunately, scientists almost had gotten nothing in developing novel applicable ones during the past half century. Even worse, due to the antibiotic abuse, many drug resistant bacteria strains have been hatched, like the super bacteria with the NDM-1 plasmid, which are seriously jeopardizing public health.

Animal antimicrobial peptides are an abundant and diverse group of antibacterial molecules that have been identified in a variety of invertebrate, plant, and animal species. They have become the rising star in the research of new antibiotics as the alternatives to conventional antibiotics due to their obvious advantages of destroying the bacteria membrane directly and have minor side effects in developing drug resistance.

One of the always emphasized research points of Dr. ZHANG Yun’s lab, the key lab of animal models and human disease mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the CAS, is to investigate the clinical application of AMPs.

2011, July, the snake cathelicdin AMP developed by Dr. ZHANG’s lab has received a national invention patent (Patent No. ZL200810058260.9). According to Dr. ZHANG, the snake cathelicdin AMP, which is highlighted by the merits of low cytoxity and hemolytic activity, has demonstrated strong antibiotic activities to over 500 clinical drug-fast bacteria strains. Meanwhile, it has well performed in the in vivo pharmacodynamic experimental tests, which include the pseudomonas aeruginosa infected cornea traumatic model, artificial material post-implantation infection model, local traumatic infection model and LSP endotoxic shock syndrome model. Those unique characteristics of snake cathelicdin peptide enable it superior to Pexiganan, the candidate medication which is under phase III clinical trail in US.

In Dr. ZHANG’s latest research, the efficacy of OH-CATH30 and its analogs, a novel cathelicidin AMP deduced from the king cobra, against drug-resistant bacteria in vitro and in vivo have been evaluated. In contrast to most AMPs, OH-CATH30 possesses potent antibacterial activity and low hemolytic activity, indicating that it is a much better candidate for the development of a new antimicrobial agent. Theis results show that OH-CATH30 and its truncated peptide, OH-CM6, exhibit strong antibacterial activity against drug-resistant clinical isolates by disrupting the bacterial cytoplasmic membrane. In addition, OH-CATH30 and its analogs were effective in the mouse models of neutropenic thigh infection and bacteremia with a high therapeutic index.

Dr. ZHANG’s continuous work of AMP has enriched the knowledge of developing novel therapeutic agents’ templates against systemic infections caused by MDR bacteria. The main findings of the latest research have been published on Antimicrobial Agents and Chemotherapy (doi:10.1128/AAC.06304-11).

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