ترغب بنشر مسار تعليمي؟ اضغط هنا

Antibody-mediated cross-linking of gut bacteria hinders the spread of antibiotic resistance

92   0   0.0 ( 0 )
 نشر من قبل Anne-Florence Bitbol
 تاريخ النشر 2019
  مجال البحث علم الأحياء فيزياء
والبحث باللغة English




اسأل ChatGPT حول البحث

The body is home to a diverse microbiota, mainly in the gut. Resistant bacteria are selected for by antibiotic treatments, and once resistance becomes widespread in a population of hosts, antibiotics become useless. Here, we develop a multiscale model of the interaction between antibiotic use and resistance spread in a host population, focusing on an important aspect of within-host immunity. Antibodies secreted in the gut enchain bacteria upon division, yielding clonal clusters of bacteria. We demonstrate that immunity-driven bacteria clustering can hinder the spread of a novel resistant bacterial strain in a host population. We quantify this effect both in the case where resistance pre-exists and in the case where acquiring a new resistance mutation is necessary for the bacteria to spread. We further show that the reduction of spread by clustering can be countered when immune hosts are silent carriers, and are less likely to get treated, and/or have more contacts. We demonstrate the robustness of our findings to including stochastic within-host bacterial growth, a fitness cost of resistance, and its compensation. Our results highlight the importance of interactions between immunity and the spread of antibiotic resistance, and argue in the favor of vaccine-based strategies to combat antibiotic resistance.



قيم البحث

اقرأ أيضاً

The affinity of antibodies (Abs) produced in vivo for their target antigens (Ags) is typically well below the maximum affinity possible. Nearly 25 years ago, Foote and Eisen explained how an affinity ceiling could arise from constraints associated wi th the acquisition of soluble antigen by B cells. However, recent studies have shown that B cells in germinal centers (where Ab affinity maturation occurs) acquire Ag not in soluble form but presented as receptor-bound immune complexes on follicular dendritic cells (FDCs). How the affinity ceiling arises in such a scenario is unclear. Here, we argue that the ceiling arises from the weakest link of the chain of protein complexes that bridges B cells and FDCs and is broken during Ag acquisition. This hypothesis explains the affinity ceiling realized in vivo and suggests that strengthening the weakest link could raise the ceiling and improve Ab responses.
The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of acti on. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements quantified binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide analogues. Moreover, by systematically modifying the mucopeptide density we gain new insights into the origin of surface stress. We propose that stress is a product of a local chemical binding factor and a geometrical factor describing the mechanical connectivity of regions affected by local binding in terms of a percolation process. Our findings place BioMEMS devices in a new class of percolative systems. The percolation concept will underpin the design of devices and coatings to significantly lower the drug detection limit and may also impact on our understanding of antibiotic drug action in bacteria.
83 - Te Wu , Feng Fu , Long Wang 2018
We study the coevolutionary dynamics of the diversity of phenotype expression and the evolution of cooperation in the Prisoners Dilemma game. Rather than pre-assigning zero-or-one interaction rate, we diversify the rate of interaction by associating it with the phenotypes shared in common. Individuals each carry a set of potentially expressible phenotypes and expresses a certain number of phenotypes at a cost proportional to the number. The number of expressed phenotypes and thus the rate of interaction is an evolvable trait. Our results show that nonnegligible cost of expressing phenotypes restrains phenotype expression, and the evolutionary race mainly proceeds on between cooperative strains and defective strains who express a very few phenotypes. It pays for cooperative strains to express a very few phenotypes. Though such a low level of expression weakens reciprocity between cooperative strains, it decelerates rate of interaction between cooperative strains and defective strains to a larger degree, leading to the predominance of cooperative strains over defective strains. We also find that evolved diversity of phenotype expression can occasionally destabilize due to the invasion of defective mutants, implying that cooperation and diversity of phenotype expression can mutually reinforce each other. Therefore, our results provide new insights into better understanding the coevolution of cooperation and the diversity of phenotype expression.
A system-level framework of complex microbe-microbe and host-microbe chemical cross-talk would help elucidate the role of our gut microbiota in health and disease. Here we report a literature-curated interspecies network of the human gut microbiota, called NJS16. This is an extensive data resource composed of ~570 microbial species and 3 human cell types metabolically interacting through >4,400 small-molecule transport and macromolecule degradation events. Based on the contents of our network, we develop a mathematical approach to elucidate representative microbial and metabolic features of the gut microbial community in a given population, such as a disease cohort. Applying this strategy to microbiome data from type 2 diabetes patients reveals a context-specific infrastructure of the gut microbial ecosystem, core microbial entities with large metabolic influence, and frequently-produced metabolic compounds that might indicate relevant community metabolic processes. Our network presents a foundation towards integrative investigations of community-scale microbial activities within the human gut.
Some bacteria and archaea possess an immune system, based on the CRISPR-Cas mechanism, that confers adaptive immunity against phage. In such species, individual bacteria maintain a cassette of viral DNA elements called spacers as a memory of past inf ections. The typical cassette contains a few dozen spacers. Given that bacteria can have very large genomes, and since having more spacers should confer a better memory, it is puzzling that so little genetic space would be devoted by bacteria to their adaptive immune system. Here, we identify a fundamental trade-off between the size of the bacterial immune repertoire and effectiveness of response to a given threat, and show how this tradeoff imposes a limit on the optimal size of the CRISPR cassette.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا