Infection by Mycobacterium abscessus subsp. massiliense poses a growing public health threat, especially to immunocompromised individuals. The pathogenicity of this mycobacterium is directly linked to its ability to form biofilms, complex structures that confer resistance to antibiotics and the host immune response. The extracellular matrix of the biofilm acts as a physical barrier, hindering the penetration of drugs and the action of the immune system, while also inducing a slow-growth state that reduces susceptibility to antibiotics. Current therapies, which involve prolonged use of multiple antibiotics, are often ineffective and cause significant side effects. Therefore, it is essential to explore new strategies targeting bacterial resistance and biofilm destruction. This narrative review explores the biofilm-forming capacity of Mycobacterium abscessus subsp. massiliense and the potential of novel therapeutic strategies. Promising approaches include inhibiting biofilm formation, developing drugs with improved penetration of the extracellular matrix, combination therapies with agents that destabilize the biofilm structure, and modulating the host immune response. Investing in research and development of new therapeutic strategies is essential to combat this resistant bacterium and improve patient outcomes.

Mycobacterium abscessus subsp. massiliense (Mabs) is an emerging nontuberculous mycobacterium associated with difficult-to-treat infections due to intrinsic antimicrobial resistance, intracellular persistence, biofilm formation, and limited responsiveness to currently available therapeutic regimens. In this context, adjuvant strategies targeting iron-dependent metabolic pathways and metal homeostasis may enhance the efficacy of conventional antimicrobials. This study investigated deferoxamine (DFO), a clinically approved iron chelator, as a potential adjuvant against Mabs using integrated in vitro and in silico approaches. Cytocompatibility was assessed using an MTT assay in RAW 264.7 macrophages and a hemolysis assay in human erythrocytes. Antimicrobial activity was evaluated through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, while interactions with clarithromycin (CLA) and amikacin (AMK) were assessed using the checkerboard method. Effects on virulence-associated phenotypes were examined through biofilm formation assays and protein quantification in extracellular vesicle-enriched fractions. Intracellular activity and modulation of inflammatory mediator gene expression were investigated in Mabs-infected RAW 264.7 macrophages through colony-forming unit (CFU) recovery and reverse transcription quantitative polymerase chain reaction (qPCR). DFO exhibited low cytotoxicity and negligible hemolytic activity under the tested conditions. Direct antimicrobial testing revealed a predominantly bacteriostatic profile (MIC = 9.75 µg/mL; MBC > 10 mg/mL), whereas checkerboard analysis suggested a synergistic interaction with CLA (FICI = 0.047), which requires further confirmation by time-kill or CFU-based combination assays. Furthermore, DFO reduced biofilm biomass, decreased protein levels in vesicle-enriched fractions, lowered intracellular bacterial burden, and modulated cytokine gene expression in infected macrophages. Molecular docking, ADME/Tox, and PASS analyses generated exploratory hypotheses regarding potential molecular interactions and pharmacological properties. Overall, these findings support DFO as a promising experimental adjuvant candidate for further investigation against Mabs, particularly in combination with clarithromycin. However, confirmation of a putative iron-restriction-associated mechanism and its translational relevance will require validation in additional clinical isolates, iron-rescue experiments, mature biofilm models, and in vivo studies.

A diabetes mellitus é uma doença metabólica crônica caracterizada pelos níveis elevados de glicose no sangue. Assim, neuropatia diabética é a complicação sintomática mais frequente em pacientes com diabetes mellitus. O objetivo deste trabalho foi analisar a prevalência de neuropatia periférica diabética em indivíduos com diabetes mellitus e os fatores de risco associados. Trata-se de uma revisão sistemática de estudos publicados nas línguas inglesa, portuguesa e espanhola, entre os anos janeiro de 2014 e junho de 2024, nas bases de dados LILACS, Medline, PubMed e SciELO. A revisão foi composta por 15 artigos. Dos artigos estudados foram contabilizados um total de 68.304 voluntários diagnosticados com Diabetes Mellitus, dos quais 42.320 (61,95%) possuem alguma neuropatia diabética. O principal subtipo de neuropatia observado foi a neuropatia periférica diabética, presente em 39.505 pacientes.