Background: Multidrug-resistant bacteria cause over 700,000 deaths annually, a figure projected to reach 10 million by 2050. Among these bacteria, the ESKAPEE group is notable for its multiple resistance mechanisms. Given the high costs of developing new antimicrobials and the rapid emergence of resistance, drug repositioning offers a promising alternative. Results: This study evaluates the antibacterial activity of sertraline and paroxetine. When tested against clinical and reference strains from the ESKAPEE group, sertraline exhibited minimum inhibitory concentration (MIC) values between 15 and 126 μg/mL, while the MIC values for paroxetine ranged from 60 to 250 μg/mL. Both drugs effectively eradicated bacterial populations within 2 to 24 h and caused morphological changes, such as protrusions and cellular fragmentation, as shown by electron scanning microscopy. Regarding their mechanisms of action as antibacterials, for the first time, increased membrane permeability was detected, as evidenced by heightened dye absorption, along with the increased presence of total proteins and dsDNA in the extracellular medium of Escherichia coli ATCC2 25922 and Staphylococcus aureus ATCC 25923, and oxidative stress was also detected in bacteria treated with sertraline and paroxetine, with reduced efficiency observed in the presence of antioxidants and higher levels of oxygen-reactive species evidenced by their reaction with 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate. The drugs also inhibited bacterial efflux pumps, increasing ethidium bromide accumulation and enhancing tetracycline activity in resistant strains. Conclusions: These findings indicate that sertraline and paroxetine could serve as alternative treatments against multidrug-resistant bacteria, as well as efflux pump inhibitors (EPIs), and they support further development of antimicrobial agents based on these compounds.

Background/Objectives: Bacterial resistance to antimicrobials is a major global health challenge, limiting the effectiveness of conventional therapies and complicating infection control. The aim of this study was to investigate the antibacterial potential of biologically synthesized silver nanoparticles (Bio-AgNP), alone and in combination with ampicillin (AMP) and enrofloxacin (ENRO), against multidrug-resistant (MDR) bacterial isolates of clinical and veterinary relevance. Methods: The antibacterial activity of Bio-AgNP, AMP, and ENRO, alone or in combination, was assessed against reference strains and MDR isolates of Escherichia coli, Salmonella enterica serovar Typhimurium and Enteritidis, and Staphylococcus aureus. Minimum inhibitory concentration (MIC) values were determined, and bacterial tolerance to prolonged antimicrobial exposure was evaluated. Additionally, assays were conducted to explore potential mechanisms of action, including cell membrane permeability and oxidative stress induction. Results: All bacterial strains developed increased MIC values after prolonged exposure to conventional antibiotics, confirming resistance. Only E. coli developed resistance to Bio-AgNP. Notably, the Bio-AgNP + AMP combination effectively restored susceptibility in E. coli, while only S. Enteritidis developed resistance to this combination upon prolonged exposure. The synergistic effect of Bio-AgNP with conventional antibiotics significantly reduced bacterial growth within two hours, compared with longer times observed in monotherapy. Mechanistic analysis suggested that the combinations increased membrane permeability, facilitating antibiotic entry. Conclusions: Bio-AgNPs combined with AMP or ENRO enhanced antibacterial activity and overcame resistance in MDR isolates, representing a promising therapeutic alternative. The biological synthesis of Bio-AgNPs, capped with organic biomolecules, supports their potential as safe adjuvants to conventional antibiotics in combating MDR bacterial infections.

This review discusses emerging in vitro and in vivo strategies for the control of Acinetobacter baumannii, a critical multidrug-resistant pathogen; the increasing isolation of strains resistant to multiple drugs, including newly developed and last-resort antibiotics, has highlighted the urgent need to pursue adjunctive therapeutic technologies. The article aims to provide an overview of alternative control approaches beyond conventional antibiotics. Emphasis is placed on strategies based on the disruption of essential metabolic pathways, nanotechnology-based approaches such as antibiotic-coated nanoparticles, in vivo bacteriophage therapy, and drug repurposing, specifically compounds such as selective serotonin reuptake inhibitors (SSRIs), as a means of exploiting already approved pharmaceuticals. By synthesizing recent findings, this review highlights current advances in the development of innovative therapeutic strategies against A. baumannii infections.

As nanopartículas de prata têm sido extensivamente pesquisadas e possuem diversas aplicações, como antimicrobiano e anticâncer, podem ser usadas nas áreas: agropecuária, biomédica, farmacêutica, têxtil, entre outras. Contudo, sua toxicidade ainda é pouco entendida. As nanopartículas podem apresentar tamanhos entre 1 – 100 nm, e a mais estudada atualmente é a de prata (AgNP). Os principais métodos de síntese são: químico e biogênico, ou “verde”, a qual é menos poluente ao meio ambiente, sustentável e simples, apesar da padronização ser mais complexa. As características morfológicas e físico-químicas se diferenciam de acordo com o método de síntese e, consequentemente, apresentam diferentes graus de toxicidade. A nanotoxicologia estuda a toxicidade das nanopartículas sobre os organismos vivos e os cientistas buscam saber a respeito das propriedades físico-químicas e sua influência na interação com o meio ambiente. Sabe-se que há diversos parâmetros que influenciam na toxicidade, como, concentração, tamanho da partícula, forma, morfologia, química da superfície, estado de aglomeração/agregação, método de síntese e o tipo de célula que é utilizada. Portanto, esta revisão visa abordar as principais vias de síntese das AgNPs, discutir as vantagens e desvantagens de cada método, os parâmetros que influenciam na toxicidade e exemplos de estudos.

A colibacilose e a salmonelose geram grandes prejuízos para a indústria avícola, diminuindo a produção e contaminando carne e ovos. Ao mesmo tempo, centenas de milhares de brasileiros são internados com pneumonia e outras infecções pulmonares todo ano, gerando um custo de centenas de milhões de reais ao ano. O problema da resistência bacteriana a antibióticos é comum a estas duas situações, e contribui para estes quadros. Com a necessidade de exploração de antimicrobianos alternativos na busca para reversão desses quadros, este projeto avaliou as propriedades antimicrobianas do óleo essencial de orégano e de nanopartículas de prata, biologicamente sintetizadas na forma de nebulização. Para isso, foram realizados testes microbiológicos que demonstraram a atividade antimicrobiana dos vapores do óleo essencial de orégano e a capacidade deste e das nanopartículas de prata biologicamente sintetizadas de reduzir 1 a 5 logs nas populações bacterianas testadas.