Human Pleural Fluid and Human Serum Albumin Modulate the Behavior of a Hypervirulent and Multidrug-Resistant (MDR) Acinetobacter baumannii Representative Strain

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.

Interaction of Acinetobacter baumannii with Human Serum Albumin: Does the Host Determine the Outcome?

“…Changes at the transcriptional level affecting genes involved in antimicrobial resistance were observed in the five different A. baumannii strains used, despite a differential behavior depending on the studied gene and strain. Results of biofilm formation were in accordance with previous observations obtained with other human fluids [16], where a reduced expression of genes involved in biofilm formation, supported by a substantial decrease in biofilm formation, was observed in all the strains. The transcriptional level of quorum sensing network genes, known to control different virulence factors, was also affected.…”

“…Supernatants from A. baumannii A118 and AB5075 cultures in LB showed the highest AHL production, suggesting down-regulation of QS and/or up-regulation of quorum quenching in the presence of HSA molecules or HS components (Figure 7). These results are consistent with a previous observation that A. baumannii AB5075 cultured in human pleural fluid produced reduced levels of AHLs [16]. The mean ± SD is informed.…”

“…The model A. baumannii strains A118 and AB5075, which show a different degree of susceptibility and virulence, were used [16,21,50,51]. Additional strains containing metallo β-lactamases, such as New Delhi metallo-β-lactamase (NDM) or oxacilinases (OXA) were used.…”

Histone-like nucleoid-structuring protein (H-NS) regulatory role in antibiotic resistance in Acinetobacter baumannii

“…S4 A). In addition, we assessed the levels of AHL using Agrobacterium tumefaciens -based solid plate assays 35 , 36 . The supernatants from cultures of AB5075 or AB5075 Δhns produced similar intensity of color, likely caused by an increase of both lactonase activity (quorum quenching) and AHL synthesis (quorum sensing) in the mutant strain (Fig.…”

“…Agrobacterium tumefaciens -based solid plate assays were carried out to detect N-Acyl Homoserine Lactone (AHL) production 42 as described in previous work 36 . Initially, 500 µL of the homogenate were loaded in a central well of 0.7% LB agar plates supplemented with 40 µg of 5-bromo-3-indolyl-b- d -galactopyranoside (X-Gal) per mL and 250 µL (OD = 2.5) of the overnight culture of Agrobacterium tumefaciens biosensor.…”