Bacterial pathogens cause many diseases in humans and are frequently well controlled by treatment with antibiotics. However, antibiotics are increasingly becoming inefficient. In addition to the well-documented cases of antibiotic resistance, persistence, characterised by relapsing infections following antibiotic treatment, is a major problem. It has been discovered recently that for many bacterial species, a proportion of bacterial cells grown in laboratory medium can enter a dormant-like state in which they are not affected by antibiotics. These bacteria are called persisters. It is thought that eventually (sometimes decades after antibiotic treatment), persisters can resume growth, accounting for relapses of infection. Salmonella is the causative agent of various diseases, ranging from gastro-enteritis to typhoid fever. We have recently discovered that upon infection of host cells, there is a dramatic increase in the proportion of the Salmonella population that forms persisters. A family of genes, named Toxin/Antitoxin modules, is known to be involved in the formation of persisters in a non-pathogenic bacterial species, but almost nothing is known about these genes in pathogenic bacteria like Salmonella. We investigate their function, particularly in relation to persistence of Salmonella to antibiotics during infection. Understanding mechanisms of action of such genes could provide ways to prevent bacteria from becoming persisters, or force them out of that state so they become re-sensitised to antibiotics.
After completing my Ph.D. at Universite Paris 5- Necker, Paris, France, in 2006 with Dr Vladimir Pelicic, I joined the CMBI in the Department of Medicine at Imperial College London as a Research Associate in the laboratory of Prof David Holden in 2007. I have been awarded a Junior Research Fellowship by Imperial College London in 2012 and started my own research group to study the formation and biology of Salmonella persisters during infection of the host in 2013. I am now a senior lecturer of the MRC Centre for Molecular Bacteriology of Infection at Imperial College London. Our work allowed me to be granted a 5y MRC Career Development Award from January 2015 to investigate the role of Toxin-antitoxin modules during Salmonella infection, and an ERC starting grant from February 2018 to investigate how persisters wake up. I am a Lister Research Prize fellow since 2017.
et al., Activity of acetyltransferase toxins involved in persister formation of Salmonella during macrophage infection, Nature Communications
Fisher RA, Gollan B, Helaine S, 2017, Persistent bacterial infections and persister cells, Nature Reviews Microbiology, Vol:15, ISSN:1740-1526, Pages:453-464
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et al., 2017, Single-cell RNA-seq ties macrophage polarization to growth rate of intracellular Salmonella, Nature Microbiology, Vol:2, ISSN:2058-5276
Fisher RA, Cheverton AM, Helaine S, 2016, Analysis of Macrophage-Induced Salmonella Persisters., Methods Mol Biol, Vol:1333, Pages:177-187