Complex and unexpected outcomes of antibiotic therapy against a polymicrobial infection

Antibiotics are our primary approach to treating complex infections, yet we have a poor understanding of how these drugs affect microbial communities. To better understand antimicrobial effects on host-associated microbial communities we treated cultured sputum microbiomes from people with cystic fibrosis (pwCF, n = 24) with 11 different antibiotics, supported by theoretical and mathematical modeling-based predictions in a mucus-plugged bronchiole microcosm. Treatment outcomes we identified in vitro that were predicted in silico were: 1) community death, 2) community resistance, 3) pathogen killing, and 4) fermenter killing. However, two outcomes that were not predicted when antibiotics were applied were 5) community profile shifts with little change in total bacterial load (TBL), and 6) increases in TBL. The latter outcome was observed in 17.8% of samples with a TBL increase of greater than 20% and 6.8% of samples with an increase greater than 40%, demonstrating significant increases in community carrying capacity in the presence of an antibiotic. An iteration of the mathematical model showed that TBL increase was due to antibiotic-mediated release of pH-dependent inhibition of pathogens by anaerobe fermentation. These dynamics were verified in vitro when killing of fermenters resulted in a higher community carrying capacity compared to a no antibiotic control. Metagenomic sequencing of sputum samples during antibiotic therapy revealed similar dynamics in clinical samples. This study shows that the complex microbial ecology dictates the outcomes of antibiotic therapy against a polymicrobial infection.Subject terms: Microbiome, Microbial ecology     

A method for identifying colonies of bacteria possessing mosquito larvicidal effects

Summary The method described provides a new, relatively rapid tool for the tracing or identification of B. thuringiensis var. israelensis among indigenous bacteria and even closely related variants of B. thuringiensis.     

Regional heterogeneity of two high affinity binding sites for 3H-WB-4101 in mouse brain

Binding studies of the tritium labeled α-adrenergic antagonist WB-4101 to mouse brain homogenate at equilibrium, reveal two binding sites: a super high affinity site (0.25 nM, 0.070 pmole/mg. protein) and a high affinity site (3.0 nM, 0.19 pmole/ mg. protein). Kinetic experiments, which measure the rates of association and dissociation of ³H-WB-4101 further confirm the existence of two binding sites. Differences in the distribution of the two sites in five regions of mouse brain are described. In addition, we present evidence suggestive of a postsynaptic localization of both binding sites.     

Melanization of the alimentary tract in lizardfishes (Teleostei, Aulopiformes, Synodontidae)

Investigating the alimentary tract in several species of lizardfishes (Synodontidae, Teleostei) of the genera Saurida, Synodus and Trachinocephalus, from various sites of their distribution, revealed melanization of the tract wall. This phenomenon was observed in several species of the genus Saurida, but not in the other two genera. This melanization is caused by layers of melanosomes rich in melanin granules and deposited within the connective tissue of the submucosa, between the muscular wall and the muscularis submucosa. From this site this black submucosa extends into the folds of the mucosa. In S. tumbil and S. filamentosa, the entire alimentary tract is black, whereas in S. macrolepis only the stomach is partially or entirely black. This phenomenon and its possible importance are discussed.