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. 2024 Jan-Dec;16(1):2357767.
doi: 10.1080/19490976.2024.2357767. Epub 2024 May 23.

Incremental increases in physiological fluid shear progressively alter pathogenic phenotypes and gene expression in multidrug resistant Salmonella

Jiseon Yang  1   2   3 , Jennifer Barrila  1   2 , Eric A Nauman  4 , Seth D Nydam  5 , Shanshan Yang  6 , Jin Park  7 , Ami D Gutierrez-Jensen  2   3 , Christian L Castro  2   3   8 , C Mark Ott  9 , Kristina Buss  6   7 , Jason Steel  6   7 , Anne D Zakrajsek  4 , Mary M Schuff  4 , Cheryl A Nickerson  1   2   3
Affiliations

Incremental increases in physiological fluid shear progressively alter pathogenic phenotypes and gene expression in multidrug resistant Salmonella

Jiseon Yang et al. Gut Microbes. 2024 Jan-Dec.

Abstract

The ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant S. Typhimurium (ST313 D23580) under different fluid shear conditions relevant to its transition from the intestinal tract to the bloodstream. We report that D23580 exhibited incremental changes in transcriptomic profiles that correlated with its pathogenic phenotypes in response to these progressive increases in fluid shear. This is the first demonstration that incremental changes in fluid shear forces alter stress responses and gene expression in any ST313 strain and offers mechanistic insight into how forces encountered by bacteria during infection might impact their disease-causing ability in unexpected ways.

Keywords: RNA-seq; RWV bioreactor; SPI-1/SPI-4; Salmonella; hydrodynamic biosystems/fluid shear; iNTS ST313/D23580.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
A series of incrementally increasing physiological fluid shear conditions progressively alters stress responses of D23580.
Figure 2.
Figure 2.
Comparative transcriptomic analysis of D23580 grown in different levels of fluid shear in the RWV.
Figure 3.
Figure 3.
Comparison of differentially expressed genes between different fluid shear levels.
Figure 4.
Figure 4.
Addition of FS3+FS4 condition: Salmonella cellular responses to incrementally increased fluid shear levels from FS1 to FS3+FS4.
Figure 5.
Figure 5.
Quantification of the fluid velocity profile and fluid shear stress in the RWV for the FS3, FS4, and FS3 + FS4 conditions.
See this image and copyright information in PMC

References

    1. CDC . Antibiotic resistance threats in the U.S. 2019. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019.
    1. CDC . COVID-19: U.S. Impact on antimicrobial resistance, special report 2022. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2022.
    1. Gordon MA, Graham S, Walsh A, Wilson L, Phiri A, Molyneux E, Zijlstra E, Heyderman R, Hart C, Molyneux M. et al. Epidemics of invasive Salmonella enterica serovar enteritidis and S. enterica Serovar typhimurium infection associated with multidrug resistance among adults and children in Malawi. Clin Infect Dis. 2008;46(7):963–17. doi:10.1086/529146. - DOI - PubMed
    1. Graham SM, Walsh AL, Molyneux EM, Phiri AJ, Molyneux ME. Clinical presentation of non-typhoidal Salmonella bacteraemia in Malawian children. Trans R Soc Trop Med Hyg. 2000;94(3):310–314. doi:10.1016/S0035-9203(00)90337-7. - DOI - PubMed
    1. Kingsley RA, Msefula CL, Thomson NR, Kariuki S, Holt KE, Gordon MA, Harris D, Clarke L, Whitehead S, Sangal V. et al. Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome Res. 2009;19(12):2279–2287. doi:10.1101/gr.091017.109. - DOI - PMC - PubMed