Abstract:
:Antimicrobial peptides (AMPs) establish the first line of host defense mechanism against invading microorganisms including bacteria, viruses, fungi and parasites. In recent years, emergence and spread of antibiotic resistance bacterial pathogens have dawn considerable interest in investigations of AMPs. The ability of AMPs to exert lethality against multiple drug-resistant (MDR) bacteria has incited promising avenues for antibiotic development. As a mode of action, most AMPs perturb the membrane organization of bacterial cells. The outer membrane lipopolysaccharide (LPS) of Gram-negative bacteria establishes a superior permeability barrier, in contrast to the peptidoglycan layer of Gram-positive bacteria. Due to LPS barrier, development of antibiotics for drug resistant Gram- negative bacteria are more complicated, with only fewer compounds in the pipeline. Recent studies have demonstrated that LPS actively regulate mode of action of AMPs on the lethality of Gram-negative bacteria. LPS, also known as endotoxin, is the primary agent for septic shock syndromes in intensive care unit killing over 120,000 people in the USA. Currently, anti-sepsis therapies are greatly lacking. Therefore, LPS has been considered as a target for the development of antimicrobial and antisepsis drugs. In recent and past few years, 3-D structures and interactions of a number of AMPs have been determined in complex with LPS micelles. These studies have generated molecular insights towards mode of action and synergistic activity of AMPs in the outer membrane. In this review, atomic resolution structures and interactions of potent AMPs with LPS are discussed providing novel insights of their mode of action.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Bhattacharjya Sdoi
10.2174/1568026615666150703121943subject
Has Abstractpub_date
2016-01-01 00:00:00pages
4-15issue
1eissn
1568-0266issn
1873-4294pii
PPL-EPUB-68551journal_volume
16pub_type
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