When the Salmonella Typhi Bacteria Gains in Resistance, it Loses in Virulence

A study led by Dr. Jordi Vila, researcher at ISGlobal and Director of the Antibiotic Resistance Initiative, shows that when Salmonella Typhi acquires resistance to quinolones and other antibiotics, it becomes less virulent. The results of the study, published in the Journal of Antimicrobial Chemotherapy, suggest that these quinolone-resistant isolates will have an impaired capacity to cross the gut mucosa and survive within the host.   

Typhoid fever is a systemic human infection caused by Salmonella enterica serovar Typhi. Every year, it causes more than 20 million infections and around 200,000 deaths, particularly in Asia. In order to cause systemic disease, the bacteria need to cross the mucosal epithelium and infect neighbouring macrophages (a type of immune cells), thus favouring their dissemination. Over the last years, the treatment of typhoid fever has changed and adapted to the emergence of drug-resistant strains. Recent reports indicate the emergence of non-typhoid Salmonella strains that are highly resistant to nalidixic acid and less susceptible to fluorquinolones (e.g. ciprofloxacin). Despite this trend, the reported prevalence of clinical Salmonella enterica isolates that are resistant to fluoroquinolones is very low. 

The goal of this study was to investigate the mechanisms of quinolone-resistance acquisition in Salmonella Typhi isolates, and its impact on virulence. For this, the researchers generated two antibiotic-resistant mutants from a Salmonella Typhi clinical isolate, and compared their susceptibility to quinolones as well as their virulence in terms of capacity to infect and survive within a human cell line. Even though the molecular mechanisms underlying antibiotic resistance turned out to be different, both mutants expressed lower levels of virulence-associated genes. This in turn decreased their capacity to infect and survive within a human cell line as well as to trigger the innate immune response. The authors conclude that, altogether, this may result in an impaired dissemination of the pathogen within the host and may explain the low frequency of Salmonella Typhi isolates that are highly resistant to ciprofloxacin.  

Reference

Ballesté-Delpierre C, Fàbrega A, Ferrer-Navarro M, Mathur R, Ghosh S, Vila J. Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants. J Antimicrob Chemother. 2015 Oct 6.