Bogati, B. | Search bioRxiv

bioRxiv2025

Sulbactam-durlobactam susceptibility among cefiderocol heteroresistant Acinetobacter

The ATTACK clinical trial for treatment of carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) isolates determined treatment with sulbactam-durlobactam to be efficacious and safe. However, other newly introduced {beta}-lactam antibiotics, including the novel cephalosporin cefiderocol, have been compromised upon clinical introduction by a type of antibiotic resistance called heteroresistance, in which only a small subpopulation of total cells exhibit phenotypic resistance. Therefore, we sought to test for sulbactam-durlobactam heteroresistance, as well as whether sulbactam-durlobactam was effective against cefiderocol heteroresistant CRAB isolates. We did not observe heteroresistance (or conventional resistance) to sulbactam-durlobactam among the 107 carbapenem-resistant Acinetobacter isolates tested, consistent with the efficacy of this new antibiotic in the ATTACK trial. Further, sulbactam-durlobactam was active against cefiderocol heteroresistant CRAB, highlighting that this antibiotic may be prioritized in relation to cefiderocol in treating CRAB infections.

microbiology↗

bioRxiv2023

Translocation of gut commensal bacteria to the brain

The gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and inflammation. Recent advances suggest a strong correlation between gut dysbiosis and neurological diseases, however, relatively little is known about how gut bacteria impact the brain. Here, we reveal that gut commensal bacteria can translocate directly to the brain when mice are fed an altered diet that causes dysbiosis and intestinal permeability, and that this also occurs without diet alteration in distinct murine models of neurological disease. The bacteria were not found in other systemic sites or the blood, but were detected in the vagus nerve. Unilateral cervical vagotomy significantly reduced the number of bacteria in the brain, implicating the vagus nerve as a conduit for translocation. The presence of bacteria in the brain correlated with microglial activation, a marker of neuroinflammation, and with neural protein aggregation, a hallmark of several neurodegenerative diseases. In at least one model, the presence of bacteria in the brain was reversible as a switch from high-fat to standard diet resulted in amelioration of intestinal permeability, led to a gradual loss of detectable bacteria in the brain, and reduced the number of neural protein aggregates. Further, in murine models of Alzheimers disease, Parkinsons disease, and autism spectrum disorder, we observed gut dysbiosis, gut leakiness, bacterial translocation to the brain, and microglial activation. These data reveal a commensal bacterial translocation axis to the brain in models of diverse neurological diseases.

neuroscience↗