Ménière’s Disease (MD) is a chronic inner ear disorder defined by recurring episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and/or fullness in the ear. Its prevalence varies by region and ethnicity, with scarce epidemiological data in the Brazilian population. Although most MD cases are sporadic, familial MD (FMD) is observed in 5% to 20% of European cases. Through exome sequencing, we have found a rare missense variant in the OTOG gene in a Brazilian individual with MD with probable European ancestry (chr11:17599671C>T), which was previously reported in a Spanish cohort. Two additional rare missense heterozygous OTOG variants were found in the same proband. Splice Site analysis showed that chr11:17599671C>T may lead to substantial changes generating exonic cis regulatory elements, and protein modelling revealed structural changes in the presence of chr11:17599671C>T, chr11:17576581G>C, and chr11:17594108C>T, predicted to highly destabilize the protein structure. The manuscript aims to replicate genes previously reported in a Spanish cohort, and the main finding is that a Brazilian patient with MD also has variants previously reported in familial MD, supporting OTOG as the most frequently mutated gene in MD.

Ménière’s Disease (MD) is a chronic inner ear disorder defined by recurring episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and/or fullness in the ear. Its prevalence varies by region and ethnicity, with scarce epidemiological data in Brazilian population. Although most MD cases are sporadic, Familial MD (FMD) is observed in 5% to 20% of European cases. By exome sequencing, we have found a rare missense variant in the OTOG gene in a Brazilian MD individual with probable European ancestry (chr11:17599671C>T), which was previously reported in a Spanish cohort. Two additional rare missense heterozygous OTOG variants were found in the same proband. Splice Site analysis showed that chr11:17599671C>T may lead to substantial changes generating exonic cis regulatory elements, and protein modelling revealed structural changes in the presence of chr11:17599671C>T, chr11:17576581G>C and chr11:17594108C>T, predicted to highly destabilize protein structure. These findings indicate that missense variants may have an additive effect leading to an unstable Otogelin and support OTOG gene as a key player in the MD pathophysiology.

Acinetobacter baumannii and Klebsiella pneumoniae are gram-negative pathogens known for their antibiotic resistance, employing mechanisms of cellular communication and nutrient uptake mediated by ABC transporters. The substrate-binding proteins (SBPs) of these transporters play a crucial role in transport across the membrane and the absorption of nutrients, such as polyamines and taurine, which are essential for bacterial survival. This study aimed to characterize and predict the structures of SBPs that transport taurine and polyamines, as well as evaluate potential interactions with ligands and inhibitors. The FASTA sequences of PotD and TauA from A. baumannii, as well as PotD, PotF, and TauA from K. pneumoniae, were obtained from databases and analyzed using specific software to predict structure and interactions. Molecular docking performed on three-dimensional models of the proteins revealed favorable free energy for the binding of the proteins to their respective ligands, corroborating data from the literature; in particular, PotF from K. pneumoniaewas identified as a dual transporter of putrescine and spermidine. Additional tests showed that vigabatrin and GABA have the potential to interact with the TauA proteins, while cystamine was found to interact with PotD from A. baumannii. These results highlight the feasibility of using these molecules as targets to inhibit nutrient uptake in resistant bacteria, paving the way for the development of new antimicrobials. Identifying these interactions may open new avenues for treating infections caused by these pathogens, contributing to more effective therapeutic strategies in combating bacterial resistance.