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Genetic determinants of staphylococcal infection

Staphylococcus aureus is able to cause a wide range of diseases. Given the emergence of antibiotic resistance and the lack of vaccines, it is important to better understand S. aureus pathogenesis.
Genetic determinants of staphylococcal infection
Accumulating evidence indicates that during S. aureus infection, the pathogen engages in an intracellular infection stage, which is important for disease progression. These infected phagocytes serve as reservoirs of disseminated infection and suggest the creation of a favourable intraphagocyte environment. However, the mechanism of S. aureus phagocyte parasitism is currently unknown.

Scientists of the EU-funded STAPHYLOMICS (Identifying host factors involved in staphylococcal infection) project were interested in the genes that are triggered within phagocytes in response to S. aureus internalisation. In this context, they employed a zebrafish model of S. aureus infection and analysed the host transcriptional response to S. aureus infection in vivo. To achieve this, they performed RNA-sequencing analysis of the two major types of phagocytes – neutrophils and macrophages, sorted from infected zebrafish larvae.

The results were annotated against the zebrafish genome assembly. Statistical analysis of differentially expressed genes in infected phagocytes in comparison to their uninfected counterparts produced some interesting results. The team performed gain and loss of function approaches subsequently to elucidate the role of these hits in S. aureus pathogenesis.

Interestingly, S. aureus was found to suppress host inflammatory signalling. Two of the inflammation-associated genes were implicated in bacterial survival. In addition, both neutrophils and macrophages responded by autophagy upon S. aureus internalisation, and scientists identified genes important in this process.

A better understanding of staphylococcal host-pathogen interaction can lead to alternative therapeutic strategies. The identification of host genes involved in controlling staphylococcal growth during infection has important clinical consequences and can provide therapeutic targets for the development of the next generation of antimicrobial drugs. Furthermore, host-targeted approaches that modulate the immune system have great potential for fighting infection. This is of utmost urgency, considering the emergence of virulent multi-drug resistant strains of S. aureus that cause significant morbidity and mortality.

Related information

Keywords

Staphylococcus aureus, STAPHYLOMICS, zebrafish, neutrophil, macrophage
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