Intracellular autolytic whole cell Salmonella vaccine prevents colonization of pathogenic Salmonella Typhimurium in chicken

Mengfei Peng; Jungsoo Joo; Zabdiel Alvarado-Martinez; Zajeba Tabashsum; Arpita Aditya; Debabrata Biswas

doi:10.1016/j.vaccine.2022.10.013

Intracellular autolytic whole cell Salmonella vaccine prevents colonization of pathogenic Salmonella Typhimurium in chicken

Vaccine. 2022 Nov 8;40(47):6880-6892. doi: 10.1016/j.vaccine.2022.10.013. Epub 2022 Oct 20.

Authors

Mengfei Peng¹, Jungsoo Joo¹, Zabdiel Alvarado-Martinez², Zajeba Tabashsum³, Arpita Aditya⁴, Debabrata Biswas⁵

Affiliations

¹ Department of Animal and Avian Sciences, University of Maryland, College Park, MD, USA.
² Biological Sciences Program - Molecular and Cellular Biology, University of Maryland, College Park, MD, USA. Electronic address: zalvara1@umd.edu.
³ Biological Sciences Program - Molecular and Cellular Biology, University of Maryland, College Park, MD, USA. Electronic address: ztabashs@umd.edu.
⁴ Department of Animal and Avian Sciences, University of Maryland, College Park, MD, USA. Electronic address: aaditya1@umd.edu.
⁵ Department of Animal and Avian Sciences, University of Maryland, College Park, MD, USA; Biological Sciences Program - Molecular and Cellular Biology, University of Maryland, College Park, MD, USA; Center for Food Safety and Security Systems, University of Maryland, College Park, MD, USA. Electronic address: dbiswas@umd.edu.

PMID: 36272875
DOI: 10.1016/j.vaccine.2022.10.013

Abstract

Salmonella enterica (SE) is a major foodborne bacterial pathogen in the United States, commonly found as the normal flora of various animals that is attributed to causing at least 1.2 million infections annually. Poultry plays a major role in disseminating SE through direct contact with live animals and consumption of contaminated products. Vaccinating poultry against SE is a sustainable approach that can reduce SE in the host, preventing future infections in humans. An intracellular autolytic SE serovar Typhimurium vaccine (STLT2^+P13+19) was developed by integrating genes 13 (holin) and 19 (lysozyme) of bacteriophage P22 into the bacterial chromosome. These were inserted downstream of sseA, an SPI-2 chaperone in SE that expresses during the intracellular phase of SE. Intracellular viability of STLT2^+P13+19 reduced by 94.42% at 24 hr compared to the wild type in chicken macrophage cells (HD-11), whereas growth rate and adhesion ability remained unchanged. Inoculating STLT2^+P13+19 in HD-11 significantly enhanced the relative log fold expression of genes associated to production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12 p40, IL-18, and GM-CSF) and Toll-like-receptors (TRL-3 and 7). Vaccination of an in vivo chicken model demonstrated significant changes in secretion of iNOS, IL-6, IL-8, IL-12, and TNF-α, as well as a reduction in the intestinal colonization of SE serovar Typhimurium. Microbiome analysis of cecal fluid using 16S rRNA gene sequencing also showed modulation of intestinal microbial composition, specifically a decrease in relative abundance of Proteobacteria and increasing Firmicutes. This study provides insight into a novel vaccine design that could make food products safer without the use of synthetic compounds.

Keywords: Bacteriophage P22; Colonization; Gut microbiota; Immunity; Intracellular autolysis; Poultry; Salmonella; Vaccine.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Chickens
Humans
Interleukin-12
Interleukin-6 / metabolism
Interleukin-8
Poultry Diseases* / microbiology
Poultry Diseases* / prevention & control
RNA, Ribosomal, 16S
Salmonella Infections, Animal* / microbiology
Salmonella Infections, Animal* / prevention & control
Salmonella Vaccines*
Salmonella enterica*
Salmonella typhimurium

Substances

Interleukin-6
Interleukin-8
RNA, Ribosomal, 16S
Salmonella Vaccines
Interleukin-12