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Biology subjects

Fait, A.

Publications and source records attributed to Fait, A..

5 recordsLinked to original sources

Inhibition of multidrug-resistant Staphylococcus aureus by commensal bacterial species from the human nose

Staphylococcus aureus is an important human pathogen. With the growing threat of antimicrobial resistance, exemplified by methicillin-resistant S. aureus (MRSA) infections requiring last-line antibiotics, alternative strategies to combat S. aureus and MRSA colonisation are needed. One promising direction is to harness interactions between S. aureus and commensal bacteria resident in the nasal passage. However, it remains unclear which bacterial species or combinations are most effective at inhibiting S. aureus, and whether this inhibition is affected by resistance to last-line antibiotics. Here, we address this gap using systematic in vitro experiments to identify commensal species or combinations that inhibit MRSA, including strains resistant to key last-resort therapies. In a combinatorial screen, we detected widespread inhibition of MRSA by commensal species, with inhibitory strength dependent on species identity and community composition. Staphylococcal commensal species produced the strongest MRSA inhibition, but we achieved similarly strong inhibition by combining Corynebacterium species with Dolosigranulum pigrum. This was linked to positive growth interactions between commensals. Importantly, we observed similar levels of MRSA inhibition by commensal species when we tested MRSA strains resistant to key anti-MRSA antibiotics, including clinical isolates. Inhibition was sustained during serial passaging experiments, with minimal MRSA adaptation upon prolonged exposure. Our results show defined combinations of nasal commensals can robustly inhibit MRSA, including strains resistant to last-resort antibiotics. This supports the potential of microbiota-based therapies to prevent or eliminate S. aureus colonisation from the human nose, including in the context of antibiotic resistance.

microbiology↗

Individual bacterial taxa drive colonisation resistance to methicillin-resistant Staphylococcus aureus in human nasal microbiome samples

Identifying bacterial interactions that determine susceptibility of human microbiomes to colonisation by pathogenic bacteria has important implications for understanding health and disease and, consequently, improving treatment and prevention. Here, we show how microbiome composition of healthy-human nasal passage samples determines susceptibility to colonisation by methicillin-resistant Staphylococcus aureus (MRSA) using a replicated microcosm approach. We find that variable MRSA population growth among samples from different individuals is associated with differences in microbial community composition. To identify individual taxa contributing to in vitro colonisation resistance, we isolate bacteria from inhibitory samples and measure their effects on MRSA in co-culture. This reveals strong MRSA inhibition by multiple Enterobacteriaceae isolates, including some which fully suppress MRSA growth in our system. Finally, by assembling nasal model communities reflecting the composition of natural nasal microbiome samples and combining drop-in and drop-out designs, we show that individual taxa can drive community-level resistance to MRSA growth. Together, our results demonstrate causal links between taxonomic composition of nasal microbiome samples and resistance to S. aureus, informing potential new microbiome-targeted interventions to manage S. aureus colonisation.

microbiology↗

Vacuolar invertase knockout enhances drought tolerance in potato plants

Drought stress is one of the most critical abiotic constraints limiting crop productivity worldwide, exacerbated by ongoing climate change and increasingly frequent extreme weather events. Stomatal regulation and osmoprotective sugar accumulation are critical adaptive mechanisms for plant survival under drought stress. Here, we characterize the enhanced drought resilience observed in CRISPR/Cas9-mediated potato, mutants in their vacuolar invertase gene (StVInv). Knockout plants exhibited improved performance under progressive drought stress and during rewatering drought, maintaining higher stomatal conductance, elevated transpiration rates, and superior photosynthetic efficiency compared to wild-type (WT) plants. These improved performance under similar transpiration rate led to higher agronomic water-use efficiency (AWUE) in stvinv plants resulting in greater biomass production despite reduced water availability. Metabolomic profiling revealed distinct adaptive strategies; stvinv plants preferentially accumulated galactinol and raffinose, indicating enhanced raffinose family oligosaccharide (RFO) metabolism. Furthermore, stvinv plants displayed lower levels of abscisic acid (ABA) and its catabolites under drought, suggesting a moderated ABA response facilitating a more risk-taking growth strategy that supports sustained growth and physiological stability. Our findings identify targeted metabolic and hormonal adjustments underlying drought resilience in potato plant, offering promising strategies for enhancing crop performance under water-limited conditions.

plant biology↗

Importance of Leaf Age in Grapevines Under Salt Stress

The combined effects of salt stress and leaf age on photosynthesis and stomatal conductance are not fully understood. Salt stress develops at different rates in various plant organs and tissues, leading to osmotic and ionic stresses. We studied the development of salt stress (30 mM NaCl) in two grapevine rootstocks by examining the gas exchange, photochemistry, and salt accumulation of leaves at different ages. Our results indicate that leaf age strongly affected photosynthesis but had a minor effect on stomatal conductance in both control and salinity conditions. Surprisingly, salt stress lowered stomatal conductance but had little effect on photosynthesis, opposite to the leaf age effects. Reduction in photosystem II efficiency explained the age-associated decline in photosynthesis, suggesting that the light-dependent phase of photosynthesis is the first process affected by leaf aging. We also found that the sodium exclusion capacity decreased as leaves matured and was age and variety dependent, indicating the importance of leaf age when sampling for salt tolerance studies. Therefore, we suggest that sampling only young leaves is missing critical information in the evaluation of salt-tolerant traits in grapevines.

plant biology↗

Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus

Antimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin in the community-associated methicillin-resistant S. aureus (CA-MRSA) strain FPR3757 (USA300). Vancomycin is used to treat serious MRSA infections, but treatment failures occur despite MRSA strains being tested susceptible according to standard susceptibility methods. Exposure to physiologically relevant concentrations of LL-37 increased the minimum inhibitory concentration (MIC) of S. aureus towards vancomycin by 75% and resulted in shortened lag-phase and increased colony formation at sub-inhibitory concentrations of vancomycin. Computer simulations using a mathematical antibiotic treatment model indicated that a small increase in MIC might decrease the efficacy of vancomycin in clearing an S. aureus infection. This prediction was supported in a Galleria mellonella infection model, where exposure of S. aureus to LL-37 abolished the antimicrobial effect of vancomycin. Thus, physiologically relevant concentrations of LL-37 reduce susceptibility to vancomycin, indicating that tissue and host-specific variations in LL-37 concentrations may influence vancomycin susceptibility in vivo.

microbiology↗