In vitro and ex vivo modeling of enteric bacterial infections

ABSTRACT

Enteric bacterial infections contribute substantially to global disease burden and mortality, particularly in the developing world. In vitro 2D monolayer cultures have provided critical insights into the fundamental virulence mechanisms of a multitude of pathogens, including Salmonella enterica serovars Typhimurium and Typhi, Vibrio cholerae, Shigella spp., Escherichia coli and Campylobacter jejuni, which have led to the identification of novel targets for antimicrobial therapy and vaccines. In recent years, the arsenal of experimental systems to study intestinal infections has been expanded by a multitude of more complex models, which have allowed to evaluate the effects of additional physiological and biological parameters on infectivity. Organoids recapitulate the cellular complexity of the human intestinal epithelium while 3D bioengineered scaffolds and microphysiological devices allow to emulate oxygen gradients, flow and peristalsis, as well as the formation and maintenance of stable and physiologically relevant microbial diversity. Additionally, advancements in ex vivo cultures and intravital imaging have opened new possibilities to study the effects of enteric pathogens on fluid secretion, barrier integrity and immune cell surveillance in the intact intestine. This review aims to present a balanced and updated overview of current intestinal in vitro and ex vivo methods for modeling of enteric bacterial infections. We conclude that the different paradigms are complements rather than replacements and their combined use promises to further our understanding of host-microbe interactions and their impacts on intestinal health.

KEYWORDS:

• Organotypic culture
• microphysiological systems
• infection models
• intestine
• monolayer cell culture
• monolayer cell culture

Disclosure statement

VML is CEO and shareholder of HepaPredict AB, as well as co-founder and shareholder of PersoMedix AB. The other authors declare no conflicts of interest.

Additional information

Funding

The work received support by the Swedish Research Council [grant agreement numbers: 2019-01837], by the EU/EFPIA/OICR/McGill/KTH/Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN grant number 875510), by the Robert Bosch Foundation, Stuttgart, Germany and by the Lillian Sagens and Curt Ericssons Research Foundation.