Acinetobacter baumannii is considered one of the prioritized ESKAPE microorganisms for the research and development of novel treatments by the World Health Organization, especially because of its remarkable persistence and drug resistance. In this review, we describe how this can be acquired by the enzymatic degradation of antibiotics, target site modification, altered membrane permeability, multidrug efflux pumps, and their ability to form biofilms. Also, the evolution of drug resistance in A. baumannii, which is mainly driven by mobile genetic elements, is reported, with particular reference to plasmid-associated resistance, resistance islands, and insertion sequences. Finally, an overview of existing, new, and alternative therapies is provided.

Burkholderia cenocepacia, an opportunistic respiratory pathogen particularly relevant for cystic fibrosis patients, is difficult to eradicate due to its high level of resistance to most clinically relevant antimicrobials. Consequently, the discovery of new antimicrobials as well as molecules capable of inhibiting its virulence is mandatory. In this regard quorum sensing (QS) represents a good target for anti-virulence therapies, as it has been linked to biofilm formation and is important for the production of several virulence factors, including proteases and siderophores. Here, we report the discovery of new diketopiperazine inhibitors of theB. cenocepaciaacyl homoserine lactone synthase CepI, and report their anti-virulence properties. Out of ten different compounds assayed against recombinant CepI, four were effective inhibitors, with IC₅₀values in the micromolar range. The best compounds interfered with protease and siderophore production, as well as with biofilm formation, and showed goodin vivoactivity in aCaenorhabditis elegansinfection model. These molecules were also tested in human cells and showed very low toxicity. Therefore, they could be considered forin vivocombined treatments with established or novel antimicrobials, to improve the current therapeutic strategies againstB.cenocepacia.

The greatest obstacle for the treatment of cystic fibrosis patients infected with the Burkholderia species is their intrinsic antibiotic resistance. For this reason, there is a need to develop new effective compounds. Glutamate racemase, an essential enzyme for the biosynthesis of the bacterial cell wall, is an excellent candidate target for the design of new antibacterial drugs. To this aim, we recombinantly produced and characterized glutamate racemase from Burkholderia cenocepacia J2315. From the screening of an in-house library of compounds, two Zn (II) and Mn (III) 1,3,5-triazapentadienate complexes were found to efficiently inhibit the glutamate racemase activity with IC₅₀ values of 35.3 and 10.0 μM, respectively. Using multiple biochemical approaches, the metal complexes have been shown to affect the enzyme activity by binding to the enzyme-substrate complex and promoting the formation of an inhibited dimeric form of the enzyme. Our results corroborate the value of glutamate racemase as a good target for the development of novel inhibitors against Burkholderia.

The process of wound healing is intricate and regulated by a network of cellular, molecular, and biochemical pathways. Acute wounds progress via distinct phases of hemostasis, inflammation, proliferation, and remodeling. Chronic wounds frequently cease to heal and exhibit resistance to conventional therapies. These types of injuries are frequently attributed to diabetes, infection, or senescence. Existing therapies are constrained due to their ineffectiveness against bacteria, inability to promote regeneration, and inadequate control over medication release. Nanotechnology presents novel methods to overcome these challenges by providing multifunctional platforms that enable biological repair and medicinal delivery. Nanoparticles, which combat germs and modulate the immune system, in addition to being intelligent carriers that react to pH, oxidative stress, or enzymatic activity, provide targeted and adaptive wound therapy. Nanocomposite hydrogels are particularly advantageous as biointeractive dressings due to their ability to maintain wound moisture while facilitating regulated drug delivery. Recent advancements indicate their potential to aid in tissue regeneration, enhance therapy precision, and address issues related to safety and translation. Nanotechnology-based approaches, especially smart hydrogels, give significant promise to transform the future of wound care due to their flexibility, adaptability, and efficiency.