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Microbes & Immunity

ORIGINAL RESEARCH ARTICLE
In vitro investigation into the dynamics between

Acinetobacter baumannii, bacteriophage, and
mammalian bronchial epithelial cells

Wei Yan, Pengfei Zhang , Kenneth K.W. To , and Sharon S.Y. Leung *

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

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.
*Corresponding author: The presence of epithelial cells could also effectively inhibit/delay the emergence of
Sharon S.Y. Leung
(sharon.leung@cuhk.edu.hk) phage resistance. These findings suggested that evaluating the in vitro antibacterial
efficiency of bacteriophage in the presence of mammalian cells may yield better
Citation: Yan W, Zhang P, predictions of the therapeutic outcomes of bacteriophage therapy.
To KKW, Leung SSY. In vitro
investigation into the dynamics
between Acinetobacter baumannii,
bacteriophage, and mammalian Keywords: Bacteriophage; Lung epithelial cells; Phage-mammalian cell interaction;
bronchial epithelial cells. Microbes Bacterial infections; Acinetobacter baumannii
& Immunity. 2024;1(1):3141.
doi: 10.36922/mi.3141
Received: March 11, 2024
Accepted: April 15, 2024 1. Introduction
Published Online: May 9, 2024 Due to limited progress in novel antibiotic development and the rapid emergence
of multidrug-resistant (MDR) bacteria, research efforts have recently focused on
Copyright: © 2024 Author(s).
1
This is an Open-Access article bacteriophage (phage) therapy. Numerous studies have provided convincing evidence of
distributed under the terms of the the safety and efficacy of phage therapy in combatting MDR pathogens. At present, the
2-4
Creative Commons Attribution in vitro antibacterial efficiency of phages has been largely evaluated in mammalian cell-
License, permitting distribution,
and reproduction in any medium, free environments before moving to the in vivo studies. While good correlations were
provided the original work is found between the in vitro and in vivo evaluations in some animal infection models,
5,6
properly cited. other studies reported that the positive in vitro results (i.e., the studied phage was found
Publisher’s Note: AccScience to be active against the bacteria of interest) failed to provide accurate predictions of the
Publishing remains neutral with in vivo treatment outcomes. Gill et al. administrated phage K through intramammary
7
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regard to jurisdictional claims in
published maps and institutional infusions to treat subclinical Staphylococcus aureus-induced bovine mastitis in lactating
affiliations. dairy cattle. Only a 16.7% cure rate was observed in the phage treatment group which
Volume 1 Issue 1 (2024) 81 doi: 10.36922/mi.3141