journal article·2019-09-09

Cholic Acid-Derived Amphiphile which Combats Gram-Positive Bacteria-Mediated Infections via Disintegration of Lipid Clusters

Sandeep Kumar, Jyoti Thakur, Kavita Yadav, Madhurima Mitra, Sanjay Pal, Arjun Ray, Siddhi Gupta, Nihal Medatwal, Ragini Gupta, Deepakkumar Mishra, Parul Rani, Siladitya Padhi, Priyanka Sharma, Arti Kapil, Aasheesh Srivastava, U. Deva Priyakumar, Ujjaini Dasgupta, Lipi Thukral, Avinash Bajaj

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Abstract

Inappropriate and uncontrolled use of antibiotics results in the emergence of antibiotic resistance, thereby threatening the present clinical regimens to treat infectious diseases. Therefore, new antimicrobial agents that can prevent bacteria from developing drug resistance are urgently needed. Selective disruption of bacterial membranes is the most effective strategy for combating microbial infections as accumulation of genetic mutations will not allow for the emergence of drug resistance against these antimicrobials. In this work, we tested cholic acid (CA) derived amphiphiles tethered with different alkyl chains for their ability to combat Gram-positive bacterial infections. In-depth biophysical and biomolecular simulation studies suggested that the amphiphile with a hexyl chain (6) executes more effective interactions with Gram-positive bacterial membranes as compared to other hydrophobic counterparts. Amphiphile 6 is effective against multidrug resistant Gram-positive bacterial strains as well and does not allow the adherence of S. aureus on amphiphile 6 coated catheters implanted in mice. Further, treatment of wound infections with amphiphile 6 clears the bacterial infections. Therefore, the current study presents strategic guidelines in design and development of CA-derived membrane-targeting antimicrobials for Gram-positive bacterial infections.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Antimicrobial Peptides and Activities · RNA Interference and Gene Delivery · Lipid Membrane Structure and Behavior

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone Faridabad-Gurgaon Expressway, Faridabad−121001, Haryana, India

Manipal Academy of Higher Education, Tiger Circle Road, Madhav Nagar, Manipal−576104, Karnataka, India

Department of Chemistry, Indian Institute of Science Education and Research, Bhopal Bypass Road, Bhauri, Bhopal−462066, Madhya Pradesh, India

Kalinga Institute of Industrial Technology, KIIT Road, Patia, Bhubaneswar−751024, Odisha, India

CSIR−Institute of Genomics and Integrative Biology, South Campus, Mathura Road, Opp: Sukhdev Vihar Bus Depot, New Delhi−110025, India

Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Professor CR Rao Road, Gachibowli, Hyderabad−500032, India

Department of Microbiology, All India Institute of Medical Sciences, Sri Aurobindo Marg, Ansari Nagar, New Delhi−110029, India

Amity Institute of Integrative Sciences and Health, Amity University, Amity Education Valley Gurugram, Panchgaon, Manesar, Gurugram−122413, Haryana, India

Funding

Council of Scientific and Industrial Research · University Grants Commission · Department of Biotechnology , Ministry of Science and Technology · All-India Institute of Medical Sciences · RCB · IGIB · DBT-RA Program in Biotechnology and Life Sciences · IISER

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