Pleural fluid and human serum albumin modulate the behavior of a hypervirulent and multidrug-resistant (MDR) Acinetobacter baumannii representative strain

PIMENTEL, CAMILA; LE, CASIN; TUTTOBENE, MARISEL ROMINA; SUBILS, TOMAS; MARTINEZ, JASMINE; SIEIRA, RODRIGO; BONOMO, ROBERT A.; ACTIS, LUIS A.; TOLMASKY, MARCELO E.; RAMÍREZ, MARÍA SOLEDAD

Congreso; World Microbe Forum; 2021

Acinetobacter baumannii is a nosocomial pathogen frequently resistant to multiple drugs and causes a wide variety of infections associated with high mortality rates. CDC?s 2019 Antibiotic Resistance Threats Report moved CRAB into the urgent threats category highlighting the importance of this pathogen. Bacterial sensing of host environmental signals has been proposed to play an important role in these adaptation processes. Recent findings from our lab showed that when exposed to different human fluids as pleural fluid (PF) and cerebrospinal fluid (CSF) or purified human serum albumin (HSA), A. baumannii A118 strain displays large-scale complex responses affecting phenotypes highly relevant to bacterial persistence and infection. In the present work, to further expand our observation, and verify at the transcriptional level the distinctive response, AB5075 (hyper-virulent and extreme-drug resistant) was exposed to HSA or PF, and the transcriptional analysis was performed.The analysis of the RNA-seq data of A. baumannii AB5075 revealed that PF and HAS significantly affects the expression of 31 and 30 coding genes, respectively (FDR adjusted P-value of 1). Genes related with quorum sensing and quorum quenching, fatty acid metabolism, motility, bacterial survival, efflux pump, biofilm, and genes involved in the transport, uptake, and iron storage were found among the affected genes by PF and/or HSA. Among the DGEs (n=11) affected by both treatment, most of them corresponded to quorum sensing (n=4) and fatty acid metabolism (n=5). To confirm the results obtained by transcriptomic analysis and discern the role of HSA as the molecule involved in triggering the differential expression of DEG genes, quantitative PCR using total RNA from A. baumannii AB5075 cells cultured in LB or LB supplemented with either PF, HSA-depleted dPF (dPF), or dPF+ 0.2% HAS, as well phenotype assays were performed. Our results indicated that components present in PF, with a strong role of HSA as the inducer molecule, can modulate the expression and behavior of the hyper-virulent and MDR A. baumannii.