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Cross-kingdom sensing: investigating platelet-released signals and bacterial responding mechanisms in bacterial lifestyles switch and biofilm formation


Biosciences Institute

Dr Chien-Yi Chang , Dr M Horsburgh , Dr N Jakubovics Friday, January 22, 2021 Competition Funded PhD Project (Students Worldwide)
Newcastle United Kingdom Microbiology

About the Project

Maintaining health balance between hosts and commensal microorganisms fulfils microbial nutritional demand and also benefits to hosts for gaining unique metabolites and “training” in host immune systems against other virulent invaders. However, occasionally, commensal bacteria detach from their original niche (e.g. skin surface or oral cavity) and enter exclusive locations (e.g. bloodstream or deeper layers of skin), which could induce their pathogenicity and cause infections. Commensal Streptococci and Staphylococci from human skin or oral cavity can cross into the bloodstream through daily tooth brushing, invasive treatments, or wounds. To survive from immune attacks in blood stream, forming aggregation or biofilm on tissue surfaces can provide shield and protection. Compared to their planktonic counterparts, bacteria embedded within biofilms show greater resistance to external challenges due to self-produced and well-organized extracellular polymeric substances, which are constantly shaped by constituent bacteria and surrounding host cells. Previous studies have suggested that forming a platelet thrombus on minor endothelial lesions can attract planktonic bacterial attachment to promote further damage, platelet aggregation, and bacterial attachment. This vicious circle will result in complex bacteria-platelet biofilm and cause severe inflammation and tissue damages such as infective endocarditis. Bacterial surface proteins or compounds have been shown to induce the activation and aggregation of platelets. Nevertheless, whether diffusible molecules released by activated platelets can interact with bacterial sensing/regulating systems and induce the regulatory switch from bacterial planktonic lifestyle toward sessile status for biofilm formation is unclear.

Bacteria, through diffusible signal molecules, can communicate within their own population and express a particular phenotype in a collective manner in response to environmental stimuli. These molecule-based communications are not limited within the bacterial community but can extend to receive and interact with host cell signalling. We hypothesise that the formation of bacteria-platelet biofilms is initiated by complex bi-direction communications between bacteria and platelets. This project aims to investigate platelet signal molecules and bacterial sensing/regulating pathways involved in biofilm formation by molecular microbiology and transcriptomics approaches. This project is to bring a multidisciplinary team of scientists for advancing our understanding in bacteria-host interactions and is expected to pave a path for developing novel strategies to maintain health balance with our commensal microbiota. The student will have the opportunity to spend time in supervisors’ laboratories in Newcastle and Liverpool for gaining outstanding training in a wide range of state-of-the-art technologies.

Informal enquiries may be made to

HOW TO APPLY 

Applications should be made by emailing with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Newcastle-Liverpool-Durham (NLD) BBSRC DTP Studentship Application Details Form (Word document) to , noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.


Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

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2. Non-antibiotic quorum sensing inhibitors acting against N-acyl homoserine lactone synthase as druggable target. Scientific Reports 2014, 4: 7245.
3. Combinatorial discovery of novel polymers resistant to bacterial attachment. Nature Biotechnology 2012, 30: 868-875.
4. Unusual long-chain N-acyl homoserine lactone production by and presence of quorum quenching activity in bacterial isolates from diseased tilapia fish. PLoS One 2012, 7: e44034.
5. Comparative genomics of Staphylococcus reveals determinants of speciation and diversification of antimicrobial defense. Frontiers in Microbiology 2018, 9: 2753.
6. Comparative transcriptomics reveals discrete survival responses of S. aureus and S. epidermidis to sapienic acid. Frontiers in Microbiology 2017, 8: 33.
7. Antimicrobial activity of poly-epsilon-lysine peptide hydrogels against Pseudomonas aeruginosa. Investigative Ophthalmology & Visual Science 2019, 60: 2536.
8. Transcriptional responses of Streptococcus gordonii and Fusobacterium nucleatum to coaggregation. Molecular Oral Microbiology 2018, 33: 450-464.
9. Distinct biological potential of Streptococcus gordonii and Streptococcus sanguinis revealed by comparative genome analysis. Scientific Reports 2017, 7: 2949.
10. StreptoBase: An oral Streptococcus mitis group genomic resource and analysis platform. PLoS One 2016, 11: e0151908.
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