Deletion of Salmonella enterica serovar Typhi tolC reduces bacterial adhesion and invasion toward host cells

Ashraf Hussain; Eugene Boon Beng Ong; Prabha Balaram; Asma Ismail; Phua Kia Kien

doi:10.3389/fmicb.2023.1301478

Deletion of Salmonella enterica serovar Typhi tolC reduces bacterial adhesion and invasion toward host cells

Front Microbiol. 2023 Nov 3:14:1301478. doi: 10.3389/fmicb.2023.1301478. eCollection 2023.

Authors

Ashraf Hussain¹, Eugene Boon Beng Ong¹, Prabha Balaram¹, Asma Ismail¹, Phua Kia Kien¹

Affiliation

¹ Institute for Research in Molecular Medicine (INFORMM), University Sains Malaysia, Penang, Malaysia.

Abstract

Background: S. Typhi is a Gram-negative bacterium that causes typhoid fever in humans. Its virulence depends on the TolC outer membrane pump, which expels toxic compounds and antibiotics. However, the role of TolC in the host cell adhesion and invasion by S. Typhi is unclear.

Objective: We aimed to investigate how deleting the tolC affects the adhesion and invasion of HT-29 epithelial and THP-1 macrophage cells by S. Typhi in vitro.

Methods: We compared the adhesion and invasion rates of the wild-type and the tolC mutant strains of S. Typhi using in vitro adhesion and invasion assays. We also measured the expression levels of SPI-1 genes (invF, sipA, sipC, and sipD) using quantitative PCR.

Results: We found that the tolC mutant showed a significant reduction in adhesion and invasion compared to the wild-type strain in both cell types. We also observed that the expression of SPI-1 genes was downregulated in the tolC mutant.

Discussion: Our results suggest that TolC modulates the expression of SPI-1 genes and facilitates the adhesion and invasion of host cells by S. Typhi. Our study provides new insights into the molecular mechanisms of S. Typhi pathogenesis and antibiotic resistance. However, our study is limited by the use of in vitro models and does not reflect the complex interactions between S. Typhi and host cells in vivo.

Keywords: Salmonella Typhi; Salmonella pathogenicity island 1; TolC; adhesion; antibiotic resistance; efflux pump protein; invasion; pathogenesis.

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 the University Sains Malaysia Enteric Diseases Research Cluster Grants (1001/PSKBP/8630011 and PSKBP/86300111) and Postgraduate Research Grant (1001/CIPPM/846046). AH was financially supported by the USM Fellowship during his study.