Resistance of Gram-Negative Bacteria to Current Antibacterial Agents and Approaches to Resolve It

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 efforts 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 β-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.

Curcumin, a Natural Antimicrobial Agent with Strain-Specific Activity

“…The cells of Gram-positive bacteria are surrounded by a thick peptidoglycan layer with an additional class of lipoteichoic acids (LTA), but they do not have an outer membrane (OM). The OM of Gram-negative bacteria is largely responsible for their resistance to a broad spectrum of antibiotics, such as β-lactams, quinolones, and colistins [ 53 ].…”

Effects of Chemical and Natural Additives on Cucumber Juice’s Quality, Shelf Life, and Safety

“…KBP had a significantly higher (p ≤ 0.05) IZD, and QPI had the lowest. The lower zones of inhibition observed in the G− organisms compared to the G+ organisms due to the peptidoglycan-containing periplasmic space and the outer membrane lipopolysaccharide layer of G− bacteria acts as a barrier, preventing the penetration of numerous environmental substances [68], including antimicrobial substances, into the organism. The periplasmic space is also known to contain enzymes capable of breaking down foreign molecules attempting to gain entry into the microorganism [69,70].…”

Penapisan Actinobacteria Akuatik Penghasil Antibakteri Dari Ikan Bandeng (Chanos chanos) dan Belanak (Mugil cephalus) dengan Metode Double-Layer Diffusion

“…Menurut Choi & Lee (2019), senyawa dengan berat molekul lebih dari 600 Da tidak dapat melewati lapisan OM, sedangkan senyawa dengan berat molekul kurang dari 600 Da dapat melewati lapisan OM melalui saluran khusus yang disebut porin. Porin merupakan outer membrane protein (OMPs) pada lapisan OM yang memungkinkan molekul kecil seperti asam amino dan sakarida kecil lewat (Breijyeh, Jubeh, & Karaman, 2020). Sementara Tabel 3.…”