Targeting pathogen adhesion: a new antimicrobial strategy?
Drug resistance is becoming a significant medical threat, hampering the efficacy of antibiotics, and facilitating the re-emergence of infectious diseases. Clinical misdiagnosis contributes to this phenomenon through prescription of unnecessary medications. Therefore, new antimicrobials and rapid, sensitive in vitro diagnostics are needed to tackle antimicrobial resistance.
Targeting pathogen adhesion
The ViBrANT project focused on pathogen adhesion, the first step in the life cycle of pathogens. “Adhesion plays a central role in virulence, dictating the progression of the infection process. By interfering with this process, we can reduce invasion and hence infection,” explains project coordinator Adrian Goldman. Bacteria adhere to each other to create biofilms; they also adhere to host cells for infection or for immune evasion. This process is facilitated partly by protein adhesin molecules, which interact with host receptors. ViBrANT research was undertaken with the support of the Marie Skłodowska-Curie Actions programme and provided multidisciplinary training to 15 early-stage researchers. Emphasis was given to the identification and characterisation of adhesins found on the surface of different bacteria and viruses. For example, scientists discovered that the M-protein of Streptococcus pyogenes interacts with different protein networks depending on the microenvironment, potentially assisting immune evasion strategies. The work on the tick-borne encephalitis virus mapped 59 host protein interactions to the viral surface, of which 56 were new – potential vaccine and drug targets. Moreover, structure and sequence determination of certain adhesins enabled a better understanding of the underlying mechanisms of action. The work on the Gram-negative trimeric autotransporter adhesins revealed important insight into the interaction of these molecules with host targets.
Point-of-care diagnostics
Collectively, the information on adhesins fed into the development of biosensors for adhesin detection, opening a route to point-of-care diagnostics. Novel tools for sensing important pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus and SARS-CoV-2 alongside epidemiological markers lay the groundwork for improved diagnosis. Another part of the project focused on coatings to prevent bacteria from adhering to surfaces. In this case, surface charge was important: by rendering the coating hydrophobic or hydrophilic, bacteria attachment was reduced by about 90 %. Monitoring genomic evolution of pathogens Researchers tracked how the opportunistic pathogen S. aureus changed its genome over a period of time in infected patients. Similarly, they monitored the evolution of P. aeruginosa strains in patients with cystic fibrosis suffering from chronic lung infections. This work highlighted the adaptive behaviour of these two important pathogens as well as the frequency by which they mutate. This is central for elucidating the emergence of antibiotic resistance. Moreover, it emphasised the need for genomic characterisation of clinical isolates during outbreaks but also for evidence-based clinical decision-making.
Health and socioeconomic impact
“ViBrANT findings have the potential to revolutionise patient care,” emphasises Goldman. Anti-adhesive coatings can be used in medical devices to prevent hospital-acquired infections, while rapid point-of-care diagnostics are key for prompt detection and treatment initiation. In terms of viruses such as SARS-CoV-2, this detection can minimise viral spread and help contain regional outbreaks. Addressing the unmet need of antimicrobial resistance requires the sensible prescription of antibiotics and the development of novel ones. According to Goldman: “The future is personalised medicine, ensuring that the drug you get is the one that is right for the infection; this can only be accommodated through specific targets that emerge from the detailed characterisation of the infection process.”
Keywords
ViBrANT, pathogen adhesion, bacteria, diagnostics, antibiotic resistance, Pseudomonas aeruginosa, Staphylococcus aureus