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Pakistan-US Science and Technology Cooperation Program
Phase 7 (2017 Deadline)

Molecular characterization and drug design targeting emerging pathogenic bacteria of Pakistan and development of an access application for the health care industry
US Partner: Alexander MacKerell, University of Maryland
Pakistan Partner: Syed Sikander Azam, Quaid-i-Azam University
Project summary
This project will develop novel, effective antibacterial therapies that can be readily translated for clinical use. It will develop web-enabled technology to allow for rapid collection and real-time analysis of novel resistant pathogens identified in hospital settings.

Progress Report

Antibiotic resistance is one of the major health problems in Pakistan due to the improper administration of antibiotics. The frequent use and misuse of antibiotics has led to the creation of antibiotic resistant super-bugs. The resistance has also become a menace worldwide. It is therefore important to address this public health threat by identifying essential drug targets in bacterial pathogens and develop new antibiotics using Computer-Aided Drug Design (CADD) approaches. According to a recent investigation regarding resistance in Pakistan in 2019, Salmonella Enterica Serovar Typhi is reported as an extensively drug resistant (XDR) Typhoid which has spread to the entire country and has affected more than 5,200 people. According to the findings of the current study, some strains of Enterobacter species isolated from hospitals of Peshawar, Pakistan were investigated against several classes of drugs and were found to be highly resistant. In addition to this, a recent report titled ‘Review on Antimicrobial Resistance’ has estimated 700,000 deaths worldwide. If the situation continues, the mortality rate will increase up to 10 million by 2050. One of the aims of the current project is to develop a web portal that will allow healthcare providers throughout Pakistan to submit information regarding new resistant pathogenic strains into a database. This information may be used to make others aware of the resistant bacterial strains. Furthermore, information based on molecular level, proteins in the bacterial strains will be identified. Site Identification by Ligand Competitive Saturation (SILCS)-aided advanced CADD approaches followed by chemical synthesis and experimental validation of drug-like compounds will identify and optimize novel potential antibiotics that can trigger and block the activity of new target proteins essential for the function of bacterial pathogens. These chemical compounds may then become new antibiotics after the required clinical trials for the treatment of resistant bacterial infections. 

Resistance to the antibiotics used to treat bacterial infections is a worldwide problem that is particularly prevalent in Pakistan. To overcome this problem it is important to quickly identify new resistant bacterial infections and develop new antibiotics to treat those infections. To facilitate this process, our program is developing a web portal that will allow physicians throughout Pakistan to submit information on new resistant bacteria into a central database. This information may be used to make other physicians aware of these resistant bacteria.

In addition, information on the DNA sequences of the resistant bacteria will be obtained and novel target proteins in the strain of bacteria will be identified. Modern computer-aided drug design approaches combined with chemical synthesis and biological experiments will then be applied to identify and optimize new chemical compounds that can bind to the target protein and block its activity, thereby stopping the bacterial infection. These chemical compounds may then be tested in clinical trials and potentially become new antibiotics for the treatment of resistant bacterial infections.