tetracycline and Diabetic-Foot

Treating patients with diabetic foot infection (DFI) is challenging because of high rates of antibiotic resistance. Therefore, to administer a suitable antibiotic treatment, it is necessary to know the antibiotic resistance patterns in DFIs.. To explore this question, we selected metagenomic data of 36 tissue samples from patients with DFI in the National Center for Biotechnology Information Sequence Read Archive database.. A total of 229 antibiotic-resistant gene (ARG) subtypes belonging to 20 ARG types were detected. The antibiotic resistome of 229 different genes in the tissue samples of patients with DFI comprised 24 core and 205 accessory resistance genes. Among the core antibiotic resistome, multidrug, tetracycline, macrolide-lincosamide-streptogramin, and beta-lactam resistance genes were the dominant categories. Procrustes analysis indicated that both the microbial community composition and mobile genetic elements (MGEs) were determinants of the ARGs. In the network analysis, 29 species were speculated to be potential hosts of 28 ARGs based on the co-occurrence results. Plasmids and transposons were the most common elements that co-occurred with ARGs.. Our study provided detailed information about antibiotic resistance patterns in DFI, which has practical implications for suggesting a more specific antibiotic choice.

Topics: Anti-Bacterial Agents; Diabetes Mellitus; Diabetic Foot; Drug Resistance, Microbial; Genes, Bacterial; Humans; Tetracycline

Diabetes and its concurrent complications impact a significant proportion of the population of the US and create a large financial burden on the American health care system. FDA-approved maggot debridement therapy (MDT), the application of sterile laboratory-reared Lucilia sericata (green bottle fly) larvae to wounds, is a cost-effective and successful treatment for diabetic foot ulcers and other medical conditions. Human platelet derived growth factor-BB (PDGF-BB) is a secreted dimeric peptide growth factor that binds the PDGF receptor. PDGF-BB stimulates cell proliferation and survival, promotes wound healing, and has been investigated as a possible topical treatment for non-healing wounds. Genetic engineering has allowed for expression and secretion of human growth factors and other proteins in transgenic insects. Here, we present a novel concept in MDT technology that combines the established benefits of MDT with the power of genetic engineering to promote healing. The focus of this study is to create and characterize strains of transgenic L. sericata that express and secrete PDGF-BB at detectable levels in adult hemolymph, whole larval lysate, and maggot excretions/ secretions (ES), with potential for clinical utility in wound healing.. We have engineered and confirmed transgene insertion in several strains of L. sericata that express human PDGF-BB. Using a heat-inducible promoter to control the pdgf-b gene, pdgf-b mRNA was detected via semi-quantitative PCR upon heat shock. PDGF-BB protein was also detectable in larval lysates and adult hemolymph but not larval ES. An alternative, tetracycline-repressible pdgf-b system mediated expression of pdgf-b mRNA when maggots were raised on diet that lacked tetracycline. Further, PDGF-BB protein was readily detected in whole larval lysate as well as larval ES.. Here we show robust, inducible expression and production of human PDGF-BB protein from two conditional expression systems in transgenic L. sericata larvae. The tetracycline-repressible system appears to be the most promising as PDGF-BB protein was detectable in larval ES following induction. Our system could potentially be used to deliver a variety of growth factors and anti-microbial peptides to the wound environment with the aim of enhancing wound healing, thereby improving patient outcome in a cost-effective manner.

Topics: Animals; Animals, Genetically Modified; Debridement; Diabetic Foot; Diptera; Female; Gene Expression; Humans; Larva; Male; Platelet-Derived Growth Factor; Recombinant Proteins; Tetracycline; Wound Healing