Harnessing innovative platforms to study and prevent acinetobacter ventilator-associated pneumonia

The National Institute of Allergy and Infectious Diseases awarded the University of Arkansas for Medical Sciences $447,720 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop and employ innovative in vitro and in vivo platforms for studying Acinetobacter baumannii ventilator-associated pneumonia (VAP) pathogenesis and prevention strategies.

The research addresses a critical gap in VAP science: A. baumannii causes approximately 30 percent of VAP cases globally, yet existing experimental models fail to capture the clinically relevant microenvironment of the intubated trachea. Standard in vitro methods neglect bacterial gene regulation changes induced by the endotracheal tube environment and the role of host proteins that mediate bacterial attachment and biofilm formation. Conventional in vivo murine pneumonia models require unnaturally high bacterial inocula and provide limited temporal resolution. The funded work will develop more physiologically representative experimental platforms to characterize bacterial virulence mechanisms, biofilm formation, and evaluate novel prevention and treatment approaches tailored to the distinct characteristics of the ventilated airway.

Performance occurs in Little Rock, Arkansas, with a period of performance through August 31, 2031. The award is a Project Grant, the standard assistance type for investigator-initiated research under the NIAID program.

Abstract

/summary ventilator-associated pneumonia (VAP) is a leading nosocomial infection globally. Notably, the ventilated trachea represents a unique environment encountered and exploited by pathogens. Intubation results in acute damage to the tracheal epithelium, resulting in inflammation and deposition of host proteins on the endotracheal tube (ETT) that can be bound by bacteria leading to subsequent biofilm formation. Moreover, the insertion of the ETT reduces mucociliary function. Combined with the obstruction of the trachea caused by the ETT, this leads to the formation of static mucus pools that can contribute to infection by shielding bacteria from both the immune response and antibiotic treatments. In all, these and other distinct characteristics of the ETT microenvironment must be taken into consideration when assessing bacterial virulence mechanisms and potential prevention and treatment options. Acinetobacter baumannii is a pathogen that causes 30% of VAP cases. Despite this, little is known regarding a. Baumannii VAP pathogenesis. This is primarily due to the lack of clinically relevant in vitro and in vivo platforms currently available that reflect characteristics of the host microenvironment described above. In fact, the most commonly employed in vitro method to assess a. Baumannii tubing adherence and biofilm formation is to incubate bacteria with the material in standard culture media. This method neglects both changes in bacterial gene regulation that could be induced by the ETT microenvironment and the impact of host factors that could bind the tubing, mediating bacterial attachment. Further, the most common in vivo method to study a. Baumannii pulmonary virulence is a murine acute pneumonia model that requires the intranasal delivery of an unnaturally high inoculum of ~109 bacteria, and the readout is bacterial load at 24-36 hours post-infection. While possibly representing characteristics of non-ventilator pneumonia, this model also fails to recapitulate details of the ETT microenvironment, implying that many findings from this model are not translatable to VAP infections. In this proposal, I will harness novel platforms to investigate a. Baumannii pathogenic mechanisms of VAP, as well identify preventative measures. In aim 1, I will employ endotracheal tubes from humans and a multi-omics approach to generate the first clinically relevant in vitro platform that can be used to study bacterial adherence/biofilm formation. For aim 2, I will use a novel murine model that I have recently adapted for use with a. Baumannii to identify the first virulence factors required for VAP pathogenesis. Finally, in aim 3, I will generate a workflow consisting of these in vitro and in vivo platforms to test prospective tubing treatments to prevent a. Baumannii VAP. In all, this research will provide innovative clinically relevant platforms that will greatly advance our understanding of VAP. Moreover, the platforms and workflow described here should be easily adaptable for other significant VAP pathogens in the future, expanding the overall impact of this work.