Here is the abstract: 
Abstract
In this study, we investigated the impact of G protein-coupled receptor (GPCR) signaling on the intracellular replication of the model pathogen Brucella neotomae. Building on a prior chemical genetics screen, we identified agonists of the Gαi-coupled adenosine A1 and dopamine D4 receptors as potent inhibitors of intracellular Brucella replication. In contrast, agonists of Gαs-coupled adenosine A2A or dopamine D1 receptors, as well as antagonists of A1 or D4 receptors, either failed to inhibit or enhanced intracellular replication. Wild-type B. neotomae induced a rapid, type IV secretion system-dependent increase in host-cell cAMP during early infection. ENBA and cilostamide prevented this infection-associated cAMP increase and completely inhibited intracellular growth; this effect was partially reversed by cell-permeable cAMP analogs. Using a real-time NanoBRET biosensor, we detected rapid Gαs activation within minutes of infection that was sustained during wild type but not ΔvirB4 infection and was abrogated by ENBA or cilostamide. Disruption of early Gαs-cAMP signaling redirected Brucella-containing vacuoles (BCVs) to replication-incompatible phagolysosomal and autophagy-associated compartments. Collectively, these data support a model in which early GPCR signaling dynamics, balancing Gαs and Gαi pathways, are critical for the establishment of productive intracellular Brucella infection.IMPORTANCEBrucella species cause chronic infections by surviving and multiplying inside immune cells. To do this, Brucella must remodel the membrane-bound compartment that surrounds it after uptake, steering it away from destructive lysosomes and toward a permissive niche where replication can occur. We found that Brucella rapidly triggers a host signaling response controlled by G protein-coupled receptors, leading to a rise in a common cellular messenger molecule (cAMP) within minutes of infection. This early signal depends on the bacterial type IV secretion system and is required to build the replication-permissive compartment. When we disrupted this signaling with small molecules, bacteria were rerouted into degradative, autophagy-associated compartments and failed to establish productive infection. These results reveal an early host signaling checkpoint that Brucella engages to establish its intracellular niche and suggest that targeting host signaling dynamics, rather than bacterial viability directly, may provide new strategies to block intracellular infection.

And link to manuscript: Host GPCR-cAMP signaling balances Gαs and Gαi activity to control intracellular Brucella infection

Poloxamer news release, "A Simple Swap Could Change How Hospitals Test Antibiotics for Drug-Resistant Infections"

We are seeking college and high school students to help with experiments to develop new ways of treating infections using highly informative in vitro infection models in the laboratory. No prior laboratory experience necessary.   Please see contact information under "Positions" to apply or learn move.

Our New Year's Eve manuscript acceptance, full text posting on ACS Infectious Diseases.  Congratulations to members of the Manetsch and Kirby Laboratories on on line publication of: "Development of CGS-15943 Adjunctives for the Disruption of Plasmid Maintenance in Multidrug Resistant E. coli." 

The manuscript describes structure activity relationship studies on a small molecule scaffold  CGS-15943.  The parent compound causes complete eviction of an IncFIA plasmid with highly selectivity in low, single-digit micromolar concentrations.   Kate Zulauf at al. previously described identification and characterization of several potent plasmid eviction compounds in our PNAS publication.  In our ACS Infectious Diseases manuscript, one portion of MInte's PhD thesis, CGS-15943 analogs were identified which were more potent than the parent compound, and with increased penetrance, An exciting step forward in our plasmid eviction work.

Forget CO2, Forget Temperature.
Selman Waksman  step over!  A big thumbs up! 

Ariane was immersed in antimicrobial resistance research on gram negatives in Ecuador prior to starting an internal medicine residency in 2022 at Salem Hospital and MGB.  In her spare time during her medical training, she will be continuing her investigation of gram-negative resistance mechanism in the Kirby lab.

BAARN would not be complete without antimicrobial medicinal chemistry.  Roman Manetsch and lab were there in force to highlight collaborative efforts on the streptothricin scaffold.