RESISTANCE ANALYSIS IN Acinetobacter baumannii AGAINST AMPICILLIN, COLISTIN AND SULBACTAM COMBINED THERAPY
Acinetobacter baumannii; resistance; colistin; transcriptomics.
Resumo em inglês: Acinetobacter baumannii is a bacterial species of significant clinical relevance and one of the main organisms that cause healthcare-associated infections. However, several A. baumanniistrains resist various antibiotic treatment options, making their treatment difficult. In the attempt to solve this problem, the use of alternative therapies has gained prominence, such as antibiotic combined therapy. Among the combined therapies used for treating carbapenem-resistant A. baumannii (CRAB), the ampicillin, colistin, and sulbactam triple therapy is a last resort treatment option. That way, it is of great importance to study and comprehend how antimicrobial resistance occurs in such extreme cases and cases of previous resort therapies, so that it is possible to search for new therapeutic targets and develop new drugs. Given that, the present work aims to analyze in vitro generated resistance in A. baumannii to the ampicillin, colistin, and sulbactam triple therapy, regarding its stability, fitness cost, and the acquired resistance mechanism of action. The results so far have shown that only two out of eight lineages submitted to in vitro evolution could thrive and survive even in an eight-fold colistin concentration above the initial minimal inhibitory concentration. Furthermore, it was possible to see that resistance remained stable even after 10 days of growth without antibiotic exposure, along with a surge of cross-resistance to synthetic antimicrobial peptides. Finally, the microbial growth analysis revealed that resistance affected the development of both lineages, which survived differently. Then, transcriptomic and proteomic analysis will be conducted to comprehend the molecular mechanism behind the acquired resistance. This work will contribute to a deeper understanding of bacterial resistance and help target prospecting for new antimicrobial therapies.