Biology subjects

Amdal, H. A.

Publications and source records attributed to Amdal, H. A..

3 recordsLinked to original sources

bioRxiv2023

Unravelling the landscape of antibiotic resistance determinants in the nasopharynx and the impact of antibiotics: a longitudinal study of preterm infants

Respiratory pathogens, commonly colonizing nasopharynx, are among the leading causes of death due to antimicrobial resistance. Yet, antibiotic resistance determinants within nasopharyngeal microbial communities remain poorly understood. Utilizing shotgun metagenomics, we investigated the nasopharynx resistome development in preterm infants, assessed early antibiotic impact on its trajectory, and explored its association with clinical covariates. Our findings revealed widespread nasopharyngeal carriage of antibiotic resistance genes (ARGs) with resistomes undergoing transient changes, including increased ARG diversity, abundance, and composition alterations due to early antibiotic exposure. ARGs associated with the critical nosocomial pathogen Serratia marcescens persisted up to 8-10 months of age, representing a long-lasting hospitalization signature. The nasopharyngeal resistome strongly correlated with microbiome composition, with inter-individual differences and postnatal age explaining most of the variation. Our report on the collateral effects of antibiotics and prolonged hospitalization underscores the urgency of further studies focused on this relatively unexplored reservoir of pathogens and ARGs.

microbiology↗

bioRxiv2023

In vitro impact of fluconazole on oral microbial communities, bacterial growth and biofilm formation

Anti-fungal agents are widely used to specifically eliminate infections by fungal pathogens. However, the specificity of anti-fungal agents has been challenged by a few studies demonstrating anti-bacterial inhibitory effects against Mycobateria and Streptomyces species. Here we evaluated for the first time the potential effect of fluconazole, the most clinically used antifungal agent, on a human oral microbiota biofilm model. The results showed that biofilm viability on blood and mitis-salivarius agar media was progressively increased in the presence of fluconazole at clinically relevant concentrations, despite of a reduction in biomass. Target PCR revealed higher proportions of Veillonella atypica, Veillonella dispar and Lactobacillus spp. in the fluconazole treated samples compared to the control, while Fusobacterium nucleatum was reduced and Streptococcus spp was not significantly affected. Further, we tested the potential impact of fluconazole using single-species models. Our results using Streptococcus mutans and Streptococcus mitis luciferase reporters showed that S. mutans planktonic growth was not significantly affected by fluconazole, while for S, mitis planktonic growth, but not biofilm viability, was inhibited at the highest concentration. Fluconazole effects on S. mitis biofilm biomass were concentration and time-dependent. Exposure for 48h to the highest concentration of fluconazole was associated with S. mitis biofilms with the most increased biomass. Potential growth inhibitory effects were further tested using four non-streptococcal species. Among these, planktonic growth of both Escherichia coli and Granulicatella adiacens were inhibited by fluconazole. Conclusions: The data indicate bacterial responses to fluconazole that extend to a broader range of bacterial species than previously anticipated from the literature, with the potential to disturb microbial biofilm communities. Future studies are warranted to further identify the breath of species for which growth may be impacted by anti-fungal agents, and possible mechanisms involved.

microbiology↗

bioRxiv2019

Conserved pheromone production, response and degradation by Streptococcus mutans

Streptococcus mutans, a bacterium with high cariogenic potential, coordinates competence for natural transformation and bacteriocin production via the XIP and CSP pheromones. CSP is effective in inducing bacteriocin responses, but not competence in chemically defined media (CDM). This is in contrast to XIP, which is a strong inducer of competence in CDM, but can also stimulate bacteriocin genes as a late response. Inter-connections between the pathways activated by the two pheromones have been characterized in certain detail in S. mutans UA159, but it is mostly unknown whether such findings are representative for the species. In this study, we used bioassays based on luciferase reporters for the bacteriocin gene cipB and the alternative sigma factor sigX to investigate various S. mutans isolates for production and response to CSP and XIP pheromones in CDM. Similar to S. mutans UA159, endogenous CSP was undetectable in the culture supernatants of all tested strains. During optimization of the bioassay using the cipB reporter, we discovered that the acivity of exogenous CSP used as a standard was reduced over time during S. mutans growth. Using a FRET-CSP reporter peptide, we found that S. mutans UA159 was indeed able to degrade CSP, and that such proteolytic activity was not significantly different in isogenic mutants with deletion of the protease gene htrA, or the competence genes sigX, oppD, and comR. CSP proteolysis was also detected in all the wild type strains, indicating that such activity is conserved in S. mutans. For the XIP pheromone, endogenous production was observed in the supernatants of all 34 tested strains at peak concentrations in culture supernatants that varied between 200 nM and 26000 nM. Transformation in the presence of exogenous XIP was detected in all, but one, of the isolates. The efficiency of transformation varied, however, among the different strains, and for those with the highest transformation rates, endogenous XIP peak concentrations in the supernatants were above 2000 nM XIP. We conclude that XIP production and inducing effect on transformation, as well as proteolytic activity leading to the inactivation of CSP are conserved functions among different S. mutans isolates. Understanding the functionality and conservation of pheromone systems in S. mutans may lead to novel strategies to prevent or treat unbalances in oral microbiomes that may favour diseases.

microbiology↗