Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It
Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It
Date
2020-03-16
Authors
Breijyeh, Zeinab
Jubeh, Buthaina
Karaman, Rafik
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
Antimicrobial resistance represents an enormous global health crisis and one of the
most serious threats humans face today. Some bacterial strains have acquired resistance to
nearly all antibiotics. Therefore, new antibacterial agents are crucially needed to overcome
resistant bacteria. In 2017, the World Health Organization (WHO) has published a list of
antibiotic-resistant priority pathogens, pathogens which present a great threat to humans and
to which new antibiotics are urgently needed the list is categorized according to the urgency of
need for new antibiotics as critical, high, and medium priority, in order to guide and promote
research and development of new antibiotics. The majority of the WHO list is Gram-negative
bacterial pathogens. Due to their distinctive structure, Gram-negative bacteria are more resistant
than Gram-positive bacteria, and cause significant morbidity and mortality worldwide. Several
strategies have been reported to fight and control resistant Gram-negative bacteria, like the
development of antimicrobial auxiliary agents, structural modification of existing antibiotics,
and research into and the study of chemical structures with new mechanisms of action and
novel targets that resistant bacteria are sensitive to. Research e orts have been made to meet
the urgent need for new treatments; some have succeeded to yield activity against resistant
Gram-negative bacteria by deactivating the mechanism of resistance, like the action of the -lactamase
Inhibitor antibiotic adjuvants. Another promising trend was by referring to nature to develop
naturally derived agents with antibacterial activity on novel targets, agents such as bacteriophages,
DCAP(2-((3-(3,6-dichloro-9H-carbazol-9-yl)-2-hydroxypropyl)amino)-2(hydroxymethyl)propane1,3-
diol, Odilorhabdins (ODLs), peptidic benzimidazoles, quorum sensing (QS) inhibitors, and
metal-based antibacterial agents.
Description
Keywords
antimicrobial, antibiotic, resistance, Gram-negative, multidrug resistance (MDR), pathogens, bacteria, alternative therapies