Rewilding catalyzes maturation of the humoral immune system.

Inbred mice used for biomedical research display an underdeveloped immune system compared with adult humans, which is attributed in part to the artificial laboratory environment. Despite representing a central component of adaptive immunity, the impact of the laboratory environment on the B cell compartment has not been investigated in detail. Here, we performed an in-depth examination of B cells following rewilding, the controlled release of inbred laboratory mice into an outdoor enclosure.

Identification of the drug/metabolite transporter 1 as a marker of quinine resistance in a NF54×Cam3.II genetic cross.

The genetic basis of resistance to quinine (QN), a drug used to treat severe malaria, has long been enigmatic. To gain further insight, we used FRG-NOD human liver-chimeric mice to conduct a genetic cross between QN-sensitive and QN-resistant parasites, which also differ in their susceptibility to chloroquine (CQ). By applying different selective conditions to progeny pools prior to cloning, we recovered 120 unique recombinant progeny.

Longitudinal Modeling of Bacterial Sexually Transmitted Infections Among Sexual Minority Men Living with HIV.

Bacterial sexually transmitted infections (BSTIs) are largely preventable, yet their rates remain high across the U.S., particularly among sexual minority men (SMM) living with HIV (LWH).

Mapping the genomic landscape of multidrug resistance in and its impact on parasite fitness.

Drug-resistant parasites have swept across Southeast Asia and now threaten Africa. By implementing a genetic cross using humanized mice, we report the identification of key determinants of resistance to artemisinin (ART) and piperaquine (PPQ) in the dominant Asian KEL1/PLA1 lineage. We mapped as the central mediator of ART resistance and identified secondary markers.

The gut microbiome, short chain fatty acids, and related metabolites in cystic fibrosis patients with and without colonic adenomas.

Background: Adults with cystic fibrosis (CF) are at increased risk for colon cancer. CF patients have reductions in intestinal bacteria that produce short chain fatty acids (SCFAs), although it is unclear whether this corresponds with intestinal SCFA levels and the presence of colonic neoplasia. The aim of this study was to compare gut microbiome and SCFA composition in patients with and without CF, and to assess associations with colonic adenomas.

Population structure of blaKPC-harbouring IncN plasmids at a New York City medical centre and evidence for multi-species horizontal transmission.

Background: Carbapenem-resistant Enterobacterales (CRE) are highly concerning MDR pathogens. Horizontal transfer of broad-host-range IncN plasmids may contribute to the dissemination of the Klebsiella pneumoniae carbapenemase (KPC), spreading carbapenem resistance among unrelated bacteria. However, the population structure and genetic diversity of IncN plasmids has not been fully elucidated.

Lack of Effect of Gluten Challenge on Fecal Microbiome in Patients With Celiac Disease and Non-Celiac Gluten Sensitivity.

Introduction: Celiac disease (CD) may be associated with gut microbial dysbiosis. Whether discrete gluten exposure in subjects with well-controlled disease on a gluten-free diet impacts the gut microbiome is unknown and may have implications for understanding disease activity and symptoms. We conducted a prospective study to evaluate the impact of gluten exposure on the gut microbiome in patients with CD and nonceliac gluten sensitivity (NCGS).

Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital.

Background: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE).

Objectives: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19.

Methods: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City.

CrrB Positively Regulates High-Level Polymyxin Resistance and Virulence in Klebsiella pneumoniae.

Polymyxin resistance (PR) threatens the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. PR frequently arises through chemical modification of the lipid A portion of lipopolysaccharide. Various mutations are implicated in PR, including in three two-component systems-CrrA/B, PmrA/B, and PhoP/Q-and the negative regulator MgrB.

A Phase 1, Placebo-controlled, Randomized, Single Ascending Dose Study and a Volunteer Infection Study to Characterize the Safety, Pharmacokinetics, and Antimalarial Activity of the Plasmodium Phosphatidylinositol 4-Kinase Inhibitor MMV390048.

Background: MMV390048 is the first Plasmodium phosphatidylinositol 4-kinase inhibitor to reach clinical development as a new antimalarial. We aimed to characterize the safety, pharmacokinetics, and antimalarial activity of a tablet formulation of MMV390048.

Methods: A 2-part, phase 1 trial was conducted in healthy adults.