Bioinformatics and Functional Assessment of Toxin-Antitoxin Systems in Staphylococcus aureus

Gul Habib,Baolin Sun,Qing Zhu

doi:10.3390/toxins10110473

Abstract

Staphylococcus aureus is a nosocomial pathogen that can cause chronic to persistent infections. Among different mediators of pathogenesis, toxin-antitoxin (TA) systems are emerging as the most prominent. These systems are frequently studied in Escherichia coli and Mycobacterial species but rarely explored in S. aureus. In the present study, we thoroughly analyzed the S. aureus genome and screened all possible TA systems using the Rasta bacteria and toxin-antitoxin database. We further searched E. coli and Mycobacterial TA homologs and selected 67 TA loci as putative TA systems in S. aureus. The host inhibition of growth (HigBA) TA family was predominantly detected in S. aureus. In addition, we detected seven pathogenicity islands in the S. aureus genome that are enriched with virulence genes and contain 26 out of 67 TA systems. We ectopically expressed multiple TA genes in E. coli and S. aureus that exhibited bacteriostatic and bactericidal effects on cell growth. The type I Fst toxin created holes in the cell wall while the TxpA toxin reduced cell size and induced cell wall septation. Besides, we identified a new TA system whose antitoxin functions as a transcriptional autoregulator while the toxin functions as an inhibitor of autoregulation. Altogether, this study provides a plethora of new as well as previously known TA systems that will revitalize the research on S. aureus TA systems.

Highlights

Staphylococcus aureus is a commensal pathogen that can cause a diverse array of infections and syndromes such as toxic shock syndrome, bacteremia, endocarditis, osteomyelitis, pneumonia, soft-tissue infection and many more [1]
The typical toxin-antitoxin (TA) system consists of a stable toxin and an unstable antitoxin and is widely distributed in bacterial genomes
The fraction of the TA system encoded by a bacterial genome varies from one pathogen to another

Summary

Introduction

Staphylococcus aureus is a commensal pathogen that can cause a diverse array of infections and syndromes such as toxic shock syndrome, bacteremia, endocarditis, osteomyelitis, pneumonia, soft-tissue infection and many more [1]. S. aureus can detect and respond to diverse environmental stimuli such as nutrient starvation and stress to increase its fitness by altering the expression of numerous genes such as the toxin-antitoxin (TA) system and two-component system [2,3]. TA system consists of two components: a toxin that can disrupt a cellular process and an antitoxin that functions as an antidote for the toxin. TA systems have been involved in virulence and persistent infections in Escherchia coli [4], Mycobacterium [5], and Salmonella [6]. They are classified into six types based on the mechanism of interaction between toxin and antitoxin [7]. In the type III TA system, the activity of the toxic protein is inhibited by the interaction with the antitoxin

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