Peeling back the many layers of competitive exclusion

John J Maurer; Ying Cheng; Adriana Pedroso; Kasey K Thompson; Shamima Akter; Tiffany Kwan; Gota Morota; Sydney Kinstler; Steffen Porwollik; Michael McClelland; Jorge C Escalante-Semerena; Margie D Lee

doi:10.3389/fmicb.2024.1342887

Peeling back the many layers of competitive exclusion

Front Microbiol. 2024 Mar 21:15:1342887. doi: 10.3389/fmicb.2024.1342887. eCollection 2024.

Affiliations

¹ School of Animal Sciences, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
² Department of Population Health, University of Georgia, Athens, GA, United States.
³ Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
⁴ Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, United States.
⁵ Department of Microbiology, University of Georgia, Athens, GA, United States.

Abstract

Baby chicks administered a fecal transplant from adult chickens are resistant to Salmonella colonization by competitive exclusion. A two-pronged approach was used to investigate the mechanism of this process. First, Salmonella response to an exclusive (Salmonella competitive exclusion product, Aviguard^®) or permissive microbial community (chicken cecal contents from colonized birds containing 7.85 Log₁₀Salmonella genomes/gram) was assessed ex vivo using a S. typhimurium reporter strain with fluorescent YFP and CFP gene fusions to rrn and hilA operon, respectively. Second, cecal transcriptome analysis was used to assess the cecal communities' response to Salmonella in chickens with low (≤5.85 Log₁₀ genomes/g) or high (≥6.00 Log₁₀ genomes/g) Salmonella colonization. The ex vivo experiment revealed a reduction in Salmonella growth and hilA expression following co-culture with the exclusive community. The exclusive community also repressed Salmonella's SPI-1 virulence genes and LPS modification, while the anti-virulence/inflammatory gene avrA was upregulated. Salmonella transcriptome analysis revealed significant metabolic disparities in Salmonella grown with the two different communities. Propanediol utilization and vitamin B12 synthesis were central to Salmonella metabolism co-cultured with either community, and mutations in propanediol and vitamin B12 metabolism altered Salmonella growth in the exclusive community. There were significant differences in the cecal community's stress response to Salmonella colonization. Cecal community transcripts indicated that antimicrobials were central to the type of stress response detected in the low Salmonella abundance community, suggesting antagonism involved in Salmonella exclusion. This study indicates complex community interactions that modulate Salmonella metabolism and pathogenic behavior and reduce growth through antagonism may be key to exclusion.

Keywords: Salmonella; antimicrobials; attenuation; competition; exclusion; pathogen.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the United States Department of Agriculture (2005–01378, 2009–03561, and VA-160130). JE-S was supported by NIH grant R35-GM130399. Carbohydrate analysis was supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, U.S. Department of Energy grant (DE-SC0015662) to Parastoo Azadi at the University of Georgia Complex Carbohydrate Research Center.