Biology subjects

Bhattarai, S. K.

Publications and source records attributed to Bhattarai, S. K..

2 recordsLinked to original sources

bioRxiv2021

Microcin MccI47 selectively inhibits enteric bacteria and reduces carbapenem-resistant Klebsiella pneumoniae colonization in vivo when administered via an engineered live biotherapeutic

BackgroundThe gastrointestinal (GI) tract is the reservoir for multidrug-resistant (MDR) pathogens, specifically carbapenem-resistant (CR) Klebsiella pneumoniae and other Enterobacteriaceae, which often lead to the spread of antimicrobial resistance genes, severe extraintestinal infections, and lethal outcomes. Selective GI decolonization has been proposed as a new strategy for preventing transmission to other body sites and minimizing spreading to susceptible individuals. ResultsHere, we purify the to-date uncharacterized class IIb microcin I47 (MccI47) and demonstrate potent inhibition of numerous Enterobacteriaceae, including multidrug-resistant clinical isolates, in vitro at concentrations resembling those of commonly prescribed antibiotics. We then genetically modify the probiotic bacterium Escherichia coli Nissle 1917 (EcN) to produce MccI47 from a stable multicopy plasmid by using MccI47 toxin production in a counterselection mechanism to engineer one of the native EcN plasmids, which renders provisions for inducible expression and plasmid selection unnecessary. We then test the clinical relevance of the MccI47-producing engineered EcN in a murine CR K. pneumoniae colonization model and demonstrate significant MccI47-dependent reduction of CR K. pneumoniae abundance after seven days of daily oral live biotherapeutic administration without disruption of the resident microbiota. ConclusionsThis study provides the first demonstration of MccI47 as a potent antimicrobial against certain Enterobacteriaceae, and its ability to significantly reduce the abundance of CR K. pneumoniae in a preclinical animal model, when delivered from an engineered live biotherapeutic product. This study serves as the foundational step towards the use of engineered live biotherapeutic products aimed at the selective removal of MDR pathogens from the GI tract

bioengineering↗

bioRxiv2021

Proanthocyanidin-enriched cranberry extract induces resilient bacterial community dynamics in a gnotobiotic mouse model

Cranberry consumption has numerous health benefits, with experimental reports showing its anti-inflammatory and anti-tumor properties. Importantly, microbiome research has demonstrated that the gastrointestinal bacterial community modulates host immunity, raising the question whether the cranberry-derived effect may be related to its ability to modulate the microbiome. Only a few studies have investigated the effect of cranberry products on the microbiome to date. Especially because cranberry is rich in dietary fibers, we do not know the extent of microbiome modulation that is caused solely by polyphenols, particularly proanthocyanidins (PACs). Since previous work has only focused on the long-term effects of cranberry extracts, in this study we investigated the effect of a water-soluble, polyphenol-rich cranberry juice extract (CJE) on the short-term dynamics of human-derived bacterial community in a gnotobiotic mouse model. CJE characterization revealed a high enrichment in PACs (57% PACs), the highest ever utilized in a microbiome study. In a 37-day experiment with a 10-day CJE intervention and 14-day recovery time, we profiled the microbiota via 16 rDNA sequencing and applied diverse time-series analytics methods to identify individual bacterial responses. We show that daily administration of CJE induces distinct dynamical patterns in bacterial abundances during and after treatment before recovering resiliently to pre-treatment levels. Specifically, we observed an increase of the immunomodulatory mucin degrading Akkermansia muciniphila after treatment, suggesting intestinal mucus accumulation due to CJE. Interestingly, this expansion coincided with an increase in the abundance of butyrate-producing Clostridia, a group of microbes known to promote numerous adaptive and innate anti-inflammatory phenotypes.

microbiology↗