pathogens Article Human Pleural Fluid and Human Serum Albumin Modulate the Behavior of a Hypervirulent and Multidrug-Resistant (MDR) Acinetobacter baumannii Representative Strain Camila Pimentel 1,† , Casin Le 1,† , Marisel R. Tuttobene 1 , Tomas Subils 2 , Jasmine Martinez 1 , Rodrigo Sieira 3 , Krisztina M. Papp-Wallace 4,5,6 , Niroshika Keppetipola 7 , Robert A. Bonomo 4,5,6 , Luis A. Actis 8 , Marcelo E. Tolmasky 1 and Maria Soledad Ramirez 1, *   Citation: Pimentel, C.; Le, C.; Tuttobene, M.R.; Subils, T.; Martinez, J.; Sieira, R.; Papp-Wallace, K.M.; Keppetipola, N.; Bonomo, R.A.; Actis, L.A.; et al. Human Pleural Fluid and Human Serum Albumin Modulate the Behavior of a Hypervirulent and Multidrug-Resistant (MDR) Acinetobacter baumannii Representative Strain. Pathogens 2021, 10, 471. https://doi.org/10.3390/ pathogens10040471 Academic Editor: Luisa De Martino Received: 21 March 2021 Accepted: 11 April 2021 Published: 13 April 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831-3599, USA; camilapimentel99@csu.fullerton.edu (C.P.); thanhle1998@csu.fullerton.edu (C.L.); mtuttobene13@gmail.com (M.R.T.); jm13070@usc.edu (J.M.); mtolmasky@fullerton.edu (M.E.T.) 2 Instituto de Procesos Biotecnológicos y Químicos de Rosario (IPROBYQ, CONICET-UNR), Rosario S2002LRK, Argentina; tomassubils@gmail.com 3 Fundación Instituto Leloir—IIBBA CONICET, Buenos Aires C1405BWE, Argentina; rsieira@leloir.org.ar 4 Research Service and GRECC, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH 44106, USA; krisztina.papp@va.gov (K.M.P.-W.); Robert.Bonomo@va.gov (R.A.B.) 5 Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA 6 CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, OH 44106, USA 7 Department of Chemistry and Biochemistry, California State University Fullerton, Fullerton, CA 92831-3599, USA; nkeppetipola@Fullerton.edu 8 Department of Microbiology, Miami University, Oxford, OH 45056, USA; actisla@miamioh.edu * Correspondence: msramirez@fullerton.edu; Tel.: +1-657-278-4562 † Both authors have equal contribution to the work. Abstract: Acinetobacter baumannii is a nosocomial pathogen capable of causing serious infections associated with high rates of morbidity and mortality. Due to its antimicrobial drug resistance profile, A. baumannii is categorized as an urgent priority pathogen by the Centers for Disease Control and Prevention in the United States and a priority group 1 critical microorganism by the World Health Organization. Understanding how A. baumannii adapts to different host environments may provide critical insights into strategically targeting this pathogen with novel antimicrobial and biological therapeutics. Exposure to human fluids was previously shown to alter the gene expression profile of a highly drug-susceptible A. baumannii strain A118 leading to persistence and survival of this pathogen. Herein, we explore the impact of human pleural fluid (HPF) and human serum albumin (HSA) on the gene expression profile of a highly multi-drug-resistant strain of A. baumannii AB5075. Differential expression was observed for ~30 genes, whose products are involved in quorum sensing, quorum quenching, iron acquisition, fatty acid metabolism, biofilm formation, secretion systems, and type IV pilus formation. Phenotypic and further transcriptomic analysis using quantitative RT-PCR confirmed RNA-seq data and demonstrated a distinctive role of HSA as the molecule involved in A. baumannii’s response. Keywords: huma serum albumin; Acinetobacter baumannii; quorum sensing; iron; human fluids 1. Introduction Acinetobacter baumannii, a nosocomial and community acquired pathogen frequently resistant to multiple drugs, causes a wide variety of infections associated with high mor- tality rates [1,2]. Highlighting the importance of A. baumannii, the CDC’s 2019 Antibiotic Pathogens 2021, 10, 471. https://doi.org/10.3390/pathogens10040471 https://www.mdpi.com/journal/pathogens