In vitro investigation into the dynamics between Acinetobacter baumannii, bacteriophage, and mammalian bronchial epithelial cells

Abstract

Antibiotic resistance is escalating due to the rapid emergence of multidrug-resistant bacteria and the stagnation in new antibiotic development. Bacteriophage, a natural enemy of bacteria, has re-emerged as a promising alternative in the post-antibiotic era. However, none of the recently completed randomized, placebo-controlled, and double-blinded clinical trials on phage therapy could confirm its efficacy. One of the major impediments is the lack of understanding of the phage, bacteria, and host body interactions. Our work investigates the dynamics between Acinetobacter baumannii, bacteriophage, and a mammalian bronchial epithelial cell line (BEAS-2B) in a coculture system. Our results demonstrated that the bactericidal effect of bacteriophage could be augmented in the presence of non-mucus-producing epithelial cells (by 3 – 5 log). Adsorption study indicated that both phages and bacteria could adhere to the epithelial cells, subsequently promoting their contact and the phage lytic effect. The presence of epithelial cells could also effectively inhibit/delay the emergence of phage resistance. These findings suggested that evaluating the in vitro antibacterial efficiency of bacteriophage in the presence of mammalian cells may yield better predictions of the therapeutic outcomes of bacteriophage therapy.