Fosmidomycin

Hospital wastewater (HWW) is a substantial environmental reservoir of antibiotic resistance genes (ARGs) and poses risks to public health and aquatic ecosystems. However, research on the diversity, transmission mechanisms, pathogenic hosts, and risks of ARGs in different HWW types is limited. This study involved the collection of HWW samples from 15 hospitals in Hefei, China, which were subsequently categorized as general hospitals (GHs) and non-general hospitals (NGHs). A 280.28-Gbp sequencing dataset was generated using a metagenomic sequencing strategy and analyzed using metagenomic assembly and binning approaches to highlight these issues in GHs and NGHs. Results showed significant differences between GHs and NGHs in ARG distribution, microbial community composition, and hosts of ARGs. Potential pathogens such as Rhodocyclaceae bacterium ICHIAU1 and Acidovorax caeni were more abundant in GHs. Furthermore, plasmid-mediated ARGs (45.21%) were more prevalent than chromosome-mediated ARGs (25.74%) in HWW, with a significantly higher proportion of plasmid-mediated ARGs in GHs compared to NGHs. The co-occurrence of ARGs and mobile genetic elements was more frequent in GHs. Additionally, the antibiotic resistome risk index was higher in GHs (38.73 ± 12.84) than NGHs (22.53 ± 11.80), indicating a greater risk of ARG transmission in GHs. This pioneering study provides valuable insights into the transmission mechanisms and hosts of ARGs in hospital settings, emphasizing the increased risk of ARG transmission in GHs.

Major facilitator superfamily (MFS) transporters in bacteria participate in both the uptake and export of ions, metabolites or toxic compounds. In rhizobia, specific MFS transporters increase resistance to plant-produced compounds and may also affect other phenotypic traits, including symbiosis with legume host plants. Here, we describe the importance of the Sinorhizobium meliloti 1021 Fsr efflux pump in resistance to selected antimicrobial compounds and in modulating biofilm formation, motility and symbiotic efficiency with alfalfa. The fsr gene (smc00990) is annotated as encoding an MFS family fosmidomycin efflux pump. Unexpectedly, both the 1021 wild type and an fsr null mutant were highly resistant to fosmidomycin. Our assays indicate that this is due to an inability to transport the antibiotic. Unlike the wild type, the fsr mutant was highly sensitive to the fosmidomycin structural analogue fosfomycin, and moderately more sensitive to hydrogen peroxide (H2O2) and deoxycholate (DOC). Root and seed exudates from alfalfa did not inhibit the growth of the wild type or fsr mutant. fsr transcription significantly increased proportionally to the concentration of fosfomycin added to cultures but was unaffected by the addition of other antibiotics, H2O2, DOC or SDS. Alfalfa seed exudate moderately increased fsr transcriptional expression. Fluorometric assays using ethidium bromide as a substrate and carbonyl cyanide m-chlorophenyl hydrazone as an energy decoupler showed that Fsr was a proton-dependent efflux pump. Biofilm formation and swimming motility were decreased and increased, respectively, in the fsr mutant, and its symbiotic efficiency with alfalfa was decreased in terms of nodule numbers per plant and plant dry weights.