Functional interplay between the ATP binding cassette Msr(D) protein and the membrane facilitator superfamily Mef(E) transporter for macrolide resistance in Escherichia coli

Macrolides have wide clinical applications in the treatment of community-acquired respiratory tract infections, among which streptococci are the most frequent causative agents. An active efflux-based mechanism of macrolide resistance, referred to as the M phenotype in streptococcal isolates, has been associated with the presence of mef genes that encode a subset of major facilitator superfamily (MFS) transporters like Mef(E). An msr(D) gene, adjacent to and co-transcribed with mef in the presence of erythromycin, has also been implicated in drug efflux, but its role remains elusive. Msr(D) belongs to the ATP binding cassette (ABC) proteins and harbors two fused nucleotide-binding domains with no membrane-spanning domains. The present work indicates that the major resistance traits of the M phenotype in Escherichia coli may be due to Msr(D) and not to Mef(E). Fluorescence microscopy using Mef(E) tagged with GFP linked low efficacy of the chimera in conferring macrolide resistance with improper subcellular localization. The active role of Msr(D) in directing Mef(E)-GFP to the cell poles was demonstrated, as was synergistic effect in terms of levels of resistance when both proteins were expressed. A trans-dominant negative mutation within ABC Msr(D) affecting MFS Mef(E) strongly suggests that both proteins can interact in vivo, and such a physical interaction was supported in vitro. This is the first reported example of a functional interplay between an ABC component and an MFS transporter. The direct involvement of Msr(D) in the efflux of macrolides remains to be demonstrated.     

Coexistence of benign phyllodes tumor and invasive ductal carcinoma in distinct breasts: case report

This report describes a rare case of coexistence of benign phyllodes tumor, which measured 9 cm in the right breast, and invasive ductal carcinoma of 6 cm in the left breast, synchronous and independent, in a 66-year-old patient. The patient underwent a bilateral mastectomy due to the size of both lesions. Such situations are rare and usually refer to the occurrence of ductal or lobular carcinoma in situ when associated with malignant phyllodes tumors, and more often in ipsilateral breast or intra-lesional.     

Recurrent and migratory reflex sympathetic dystrophy in children

Reflex sympathetic dystrophy is a syndrome characterized by superficial pain and tenderness associated with swelling, vasomotor instability, and dystrophic changes of the skin. In children, it is rarely reported and is felt to have a more benign and self-limited course. This case illustrates that, in children, reflex sympathetic dystrophy can occur without any previous history of trauma, and may be recurrent and migratory. A review of the literature is included. An 11-year-old girl, with no history of trauma, presented in 1992 with spontaneous onset of right leg pain. She was diagnosed with reflex sympathetic dystrophy, and she was treated unsuccessfully with oral medications. Her symptoms then resolved in 2 weeks after receiving epidural anaesthesia and aggressive physical therapy. Over the next 5 years, she presented to the paediatric rehabilitation clinic three times with recurrent RSD in her bilateral arms. The first two times were refractory to conservative management and resolved with four stellate ganglion blocks. The third recurrence persisted with three stellate ganglion blocks and resolved with gabapentin.     

Erratum to: The conversion rate of tuberculosis screening tests during biological therapies in patients with rheumatoid arthritis

Clinical Rheumatology -