In vitro and intracellular activity of vaborbactam combined with ß-lactams against Mycobacterium abscessus.

OBJECTIVES: Mycobacterium abscessus has emerged as an opportunistic pathogen responsible for lung infections, especially in cystic fibrosis patients. In spite of the production of the broad-spectrum ß-lactamase BlaMab, the carbapenem imipenem is recommended in the initial phase of the treatment of pulmonary infections. Here, we determine whether the addition of vaborbactam, a second-generation ß-lactamase inhibitor belonging to the boronate family, improves the activity of ß-lactams against M. abscessus. METHODS: The activity of ß-lactams, alone or in combination with vaborbactam, was evaluated against M. abscessus CIP104536 by determining MICs, time-killing and intramacrophage activity. Kinetic parameters for the inhibition of BlaMab by vaborbactam were determined by spectrophotometry. RESULTS: The combination of vaborbactam (8 mg/L) with ß-lactams decreased more than 8 times the MIC of amoxicillin (from >1024 to 128 mg/L) and 2 times the MICs of meropenem (from 16 to 8 mg/L) and imipenem (from 4 to 2 mg/L). The reduction of the MICs was less than that obtained with avibactam at 4 mg/L for amoxicillin (from >1024 to 16 mg/L, more than 64 times less) and for meropenem (from 16 to 4 mg/L, 4 times less). In vitro and intracellularly, M. abscessus was not killed by the meropenem/vaborbactam combination, in spite of significant in vitro inhibition of BlaMab by vaborbactam. CONCLUSIONS: Inhibition of BlaMab by vaborbactam decreases the MIC of ß-lactams, including that of meropenem. As meropenem/vaborbactam is clinically available, this combination offers an alternative therapeutic option that should be evaluated for the treatment of pulmonary infections due to M. abscessus.

Differentiation of Andean and Mesoamerican accessions in a proposed core collection of grain amaranths.

Grain amaranths are made up of three New World species of pseudo-cereals with C4 photosynthesis from the dicotyledonous family Amaranthaceae and the genus Amaranthus. They originate in two ecoregions of the Americas, namely, the inter-Andean valleys of South America and the volcanic axis and lowlands of Mexico and Central America. These correspond to two centers of domestications for Andean and Mesoamerican crops, with one cultivated species found in the first region and two found in the latter region. To date, no core collection has been made for the grain amaranths in the United States Department of Agriculture (USDA) germplasm system. In this study, our objective was to create a core for the 2,899 gene bank accessions with collection site data by town or farm site of which 1,090 have current geo-referencing of latitude and longitude coordinates. We constituted the core with 260 genotypes of Amaranthus, which we evaluated with 90 single-nucleotide polymorphism markers. Our goal was to distinguish between Andean and Mesoamerican gene pools of amaranths, including the cultivated species and three possible progenitor or wild relative ancestors along with two more species in an outgroup. Population structure, clustering, and discriminant analysis for principal components showed that Andean species Amaranthus caudatus and Amaranthus quitensis shared fewer alleles with Mesoamerican species Amaranthus cruentus and Amaranthus hypochondriacus, compared to each group individually. Amaranthus hybridus was a bridge species that shared alleles with both regions. Molecular markers have the advantage over morphological traits at quickly distinguishing the Andean and Mesoamerican cultivars and have the added benefit of being useful for following inter-species crosses and introgression.

Allelic Diversity at Abiotic Stress Responsive Genes in Relationship to Ecological Drought Indices for Cultivated Tepary Bean, Phaseolus acutifolius A. Gray, and Its Wild Relatives.

Some of the major impacts of climate change are expected in regions where drought stress is already an issue. Grain legumes are generally drought susceptible. However, tepary bean and its wild relatives within Phaseolus acutifolius or P. parvifolius are from arid areas between Mexico and the United States. Therefore, we hypothesize that these bean accessions have diversity signals indicative of adaptation to drought at key candidate genes such as: Asr2, Dreb2B, and ERECTA. By sequencing alleles of these genes and comparing to estimates of drought tolerance indices from climate data for the collection site of geo-referenced, tepary bean accessions, we determined the genotype x environmental association (GEA) of each gene. Diversity analysis found that cultivated and wild P. acutifolius were intermingled with var. tenuifolius and P. parvifolius, signifying that allele diversity was ample in the wild and cultivated clade over a broad sense (sensu lato) evaluation. Genes Dreb2B and ERECTA harbored signatures of directional selection, represented by six SNPs correlated with the environmental drought indices. This suggests that wild tepary bean is a reservoir of novel alleles at genes for drought tolerance, as expected for a species that originated in arid environments. Our study corroborated that candidate gene approach was effective for marker validation across a broad genetic base of wild tepary accessions.