Gram-negative bacteria act as a reservoir for aminoglycoside antibiotics that interact with host factors to enhance bacterial killing in a mouse model of pneumonia

Abstract

In vitro exposure of multiple Gram-negative bacteria to an aminoglycoside (AG) antibiotic has previously been demonstrated to result in bacterial alterations that interact with host factors to suppress Gram-negative pneumonia. However, the mechanisms resulting in suppression are not known. Here, the hypothesis that Gram-negative bacteria bind and retain AGs, which are introduced into the lung and interact with host defenses to affect bacterial killing, was tested. Following in vitro exposure of one of several, pathogenic Gram-negative bacteria to the AG antibiotics kanamycin or gentamicin, AGs were detected in bacterial cell pellets (up to 208 μg/mL). Using inhibitors of AG binding and internalization, the bacterial outer membrane was implicated as the predominant kanamycin and gentamicin reservoir. Following intranasal administration of gentamicin-bound bacteria or gentamicin solution at the time of infection with live, AG-naïve bacteria, gentamicin was detected in the lungs of infected mice (up to 8 μg/g). Co-inoculation with gentamicin-bound bacteria resulted in killing of AG-naïve bacteria by up to 3-log10, mirroring the effects of intranasal gentamicin treatment. In vitro killing of AG-naïve bacteria mediated by kanamycin-bound bacteria required the presence of detergents or pulmonary surfactant, suggesting that increased bacterial killing inside the murine lung is facilitated by the detergent component of pulmonary surfactant. These findings demonstrate that Gram-negative bacteria bind and retain AGs that can interact with host-derived pulmonary surfactant to enhance bacterial killing in the lung. This may help explain why AGs appear to have unique efficacy in the lung and might expand their clinical utility.

Agricultural Significance of Antibiotic Resistance Pattern in Selected Nitrogen Fixing Bacteria Strains

“…were susceptible to kanamycin, showing similar responses to Psuedomonas, Ancinebacter, K. pneumoniae, A. bauannii, Proteus and Bacillus spp. were found to be susceptible to Kanamycin in the report of Palmer et al 2020, Simpson et al 2021Christiaan et al 2022. In the findings of Carbello et al 2013; it was observed that 66.71% of the gram-negative bacteria were resistant to tetracycline while our report show that 70% of the gram-negative Bradhyrhizobium spp.…”

A Mild catalyzed imino Diels-Alder reaction for the synthesis of N-(2-(o-tolyl)-1,2,3,4-tetrahydroquinoline-4-yl)formamide derivatives as regulators of Quorum Sensing in Pseudomona Aeruginosa

“…All compounds exhibited growth inhibition effects as early as 4 hours, particularly at concentrations of 50 and 75 µg/mL. Compared those results with the positive control (Gentamycin 10 µg/mL), we notice the remarkable effectiveness and potency of this drug [40], [53], [54]. Regarding cytotoxicity control (yellow line), it is corroborated that the solvent used (DMSO) for the preparation of stock solutions of the derivatives did not influence the bacteria growth.…”