The results of this study suggest that efflux is an important mechanism of fosfomycin resistance and AbaF is involved in fosfomycin resistance in A. baumannii. AbaF also seems to play a role in biofilm formation and virulence of A. baumannii.

No abstract

Objectives The emergence of MDR Gram-negative pathogens and increasing prevalence of chronic infections presents an unmet need for the discovery of novel antibacterial agents. The aim of this study was to evaluate the biological properties of a small molecule, IITR06144, identified in a phenotypic screen against the Gram-negative model organism Escherichia coli. Methods A small-molecule library of 10 956 compounds was screened for growth inhibition against E. coli ATCC 25922 at concentration 50 μM. MICs of lead compounds were determined by the broth microdilution method. Time–kill kinetics, anti-persister activity, spontaneous frequency of resistance, biofilm inhibition and disruption were assessed by standard protocols. Resistant mutants were generated by serial passaging followed by WGS. In vitro toxicity studies were carried out via the MTT assay. In vivo toxicity and efficacy in a mouse model were also evaluated. Results IITR06144 was identified as the most promising candidate amongst 29 other potential antibacterial leads, exhibiting the lowest MIC, 0.5 mg/L. IITR06144 belongs to the nitrofuran class and exhibited broad-spectrum bactericidal activity against most MDR bacteria, including the ‘priority pathogen’, carbapenem-resistant Acinetobacter baumannii. IITR06144 retained its potency against nitrofurantoin-resistant clinical isolates. It displayed anti-persister, anti-biofilm activity and lack of spontaneous resistance development. IITR06144 demonstrated a large therapeutic index with no associated in vitro and in vivo toxicity. Conclusions In the light of excellent in vitro properties displayed by IITR06144 coupled with its considerable in vivo efficacy, further evaluation of IITR06144 as a therapeutic lead against antibiotic-resistant infections is warranted.

Infirmity and death from diseases caused by unsafe food are a continual hazard to communal health safety and socio-economic growth throughout the world. Chemical preservatives are associated with health hazards and toxicity issues. In the study reported here, 200 soil isolates from Western Himalayan region in India were screened for potential antibacterial activity against food-borne pathogens. This study led to the isolation of a bacterial strain belonging to the Genus Bacillus and was designated as RPT-0001. The associated antibacterial activity was sensitive to pronase E treatment. Bioassay-guided fractionation using reverse phase high performance liquid chromatography (RP-HPLC) led to isolation of the antibacterial peptide designated as RPT-0001. The molecular weight of RPT-0001 was determined by electro-spray ionization mass spectroscopy (ESI-MS) as 276.9 Da. RPT-0001 was inhibitory to both Gram-negative and Grampositive food-borne bacteria tested. The characteristics of RPT-0001 do not match with that of any other known antibacterial peptides produced by Bacillus sp. or related genera. Purified RPT-0001 was successfully used in synthesis of silver nanoparticles effective against food-borne pathogenic bacteria. The antibacterial peptide and silver nanoparticles synthesized utilizing it as a capping and reducing agent hold promising potential in food preservation, in packaging material and as a therapeutic agent in the treatment of foodborne infections.