Evaluating how bipa contributes to yersinia pestis pathogenesis during pneumonic plague

The National Institute of Allergy and Infectious Diseases awarded East Carolina University $223,957 on September 2, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to evaluate how bactericidal permeability-increasing protein-induced protein A (BIPA) contributes to Yersinia pestis pathogenesis during pneumonic plague.

The research will define BIPA's function in early events of pneumonic plague and identify proteins regulated by BIPA that contribute to pathogenesis. The work employs bacterial mutants alongside in vitro, ex vivo, and in vivo murine infection models to determine whether BIPA contributes to bacterial adherence to mammalian cells, whether BIPA's role in resistance to BPI and neutrophils is important in vivo, and to identify BIPA-regulated proteins that enhance virulence and enable Y. pestis to subvert host defense strategies.

Performance takes place in Greenville, North Carolina through August 31, 2028.

Abstract

Yersinia pestis is one of the deadliest pathogens known to man. Due to its success as a pathogen, study of Y. Pestis has been critical to our understanding of bacterial pathogenesis as a field. This proposal introduces bactericidal permeability-increasing protein (BPI)-induced protein a (BIPA) as an important virulence factor that regulates specific proteins that play a critical role in the host/pathogen interactions that define pneumonic plague. BIPA regulates proteins at the translational level, and we show that IT contributes to Y. Pestis adherence to mammalian cells and resistance to neutrophil-mediated killing of bacteria. Thus, BIPA aids Y. Pestis in subverting host defense strategies during pneumonic plague. The objective of this work is to define the function of the BIPA in the early events of pneumonic plague, and to identify proteins regulated by BIPA that contribute to pathogenesis. Our preliminary work shows that BIPA 1. May regulate proteins that contribute to bacterial adherence. 2. Contributes to bacterial resistance to BPI and neutrophils; and 3. Specifically regulates a number of proteins upon its induction by BPI. In this proposal we will use bacterial mutants in tandem with in vitro, EX vivo, and in vivo murine infection to determine if BIPA contributes to adherence, if the role of BIPA in resistance to BPI is important in vivo, and we will identify BIPA-regulated proteins that contribute to virulence.