Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing serious nosocomial infections, which is considered as the most threatening Gram-negative bacteria (GNB). Outer membrane protein A (OmpA), a major component of outer membrane proteins (OMPs) in GNB, is a key virulence factor which mediates bacterial biofilm formation, eukaryotic cell infection, antibiotic resistance and immunomodulation. The characteristics of OmpA in Escherichia coli (E. coli) have been extensively studied since 1974, but only in recent years researchers started to clarify the functions of OmpA in A. baumannii. In this review, we summarized the structure and functions of OmpA in A. baumannii (AbOmpA), collected novel therapeutic strategies against it for treating A. baumannii infection, and emphasized the feasibility of using AbOmpA as a potential therapeutic target.

New Delhi metallo-β-lactamase-1 (NDM-1) is the most prevalent type of metallo-β-lactamase and hydrolyzes almost all clinically used β-lactam antibiotics. Here we show that the antimicrobial peptide thanatin disrupts the outer membrane of NDM-1-producing bacteria by competitively displacing divalent cations on the outer membrane and inducing the release of lipopolysaccharides. In addition, thanatin inhibits the enzymatic activity of NDM-1 by displacing zinc ions from the active site, and reverses carbapenem resistance in NDM-1-producing bacteria in vitro and in vivo. Thus, thanatin’s dual mechanism of action may be useful for combating infections caused by NDM-1-producing pathogens.

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Cationic antimicrobial peptides (AMPs) and polymers are active against many multidrug-resistant (MDR) bacteria, but only a limited number of these compounds are in clinical use due to their unselective toxicity. The typical strategy for achieving selective antibacterial efficacy with low mammalian cell toxicity is through balancing the ratio of cationicity to hydrophobicity. Herein, we report a cationic nanoparticle self-assembled from chitosan-graft-oligolysine (CSM5-K5) chains with ultralow molecular weight (1450 Da) that selectively kills bacteria. Further, hydrogen bonding rather than the typical hydrophobic interaction causes the polymer chains to be aggregated together in water into small nanoparticles (with about 37 nm hydrodynamic radius) to concentrate the cationic charge of the lysine. When complexed with bacterial membrane, these cationic nanoparticles synergistically cluster anionic membrane lipids and produce a greater membrane perturbation and antibacterial effect than would be achievable by the same quantity of charge if dispersed in individual copolymer molecules in solution. The small zeta potential (+15 mV) and lack of hydrophobicity of the nanoparticles impedes the insertion of the copolymer into the cell bilayer to improve biocompatibility. In vivo study (using a murine excisional wound model) shows that CSM5-K5 suppresses the growth of methicillin-resistant Staphylococcus aureus (MRSA) bacteria by 4.0 orders of magnitude, an efficacy comparable to that of the last resort MRSA antibiotic vancomycin; it is also noninflammatory with little/no activation of neutrophils (CD11b and Ly6G immune cells). This study demonstrates a promising new class of cationic polymers-short cationic peptidopolysaccharides-that effectively attack MDR bacteria due to the synergistic clustering of, rather than insertion into, bacterial anionic lipids by the concentrated polymers in the resulting hydrogen-bonding-stabilized cationic nanoparticles.