The Mechanism of Action of Ginkgolic Acid (15:1) against Gram-Positive Bacteria Involves Cross Talk with Iron Homeostasis

The increasing emergence of infectious diseases associated with multidrug-resistant Gram-positive pathogens has raised the urgent need to develop novel antibiotics. GA (15:1) is a natural product derived from Ginkgo biloba and possesses a wide range of bioactivities, including antimicrobial activity.

Molecular Engineering of Polymyxin B for Imaging and Treatment of Bacterial Infections

The emergence of multi-drug resistant bacteria and the lack of novel antibiotics to combat them have led to the revival of polymyxin B, a previously abandoned antibiotic due to its potential nephrotoxicity and neurotoxicity. To facilitate its widely clinical applications, increasing effort has been devoted to molecularly engineer polymyxin B for the targeted imaging and effective treatment of bacterial infections. Herein, the molecular engineering strategies will be summarized in this mini review, with selected recent advances for illustration. Perspective of the challenges and trends in this exciting and eagerly anticipated research area will also be provided in the end. We hope this mini review will inspire researchers from diverse fields to bring forward the next wave of exploiting molecular engineering approaches to propel the “old” polymyxin B to “new” clinical significance in combating bacterial infections.

Myxopyronin B inhibits growth of a Fidaxomicin-resistant Clostridioides difficile isolate and interferes with toxin synthesis

The anaerobic, gastrointestinal pathogen Clostridioides difficile can cause severe forms of enterocolitis which is mainly mediated by the toxins it produces. The RNA polymerase inhibitor Fidaxomicin is the current gold standard for the therapy of C. difficile infections due to several beneficial features including its ability to suppress toxin synthesis in C. difficile. In contrast to the Rifamycins, Fidaxomicin binds to the RNA polymerase switch region, which is also the binding site for Myxopyronin B. Here, serial broth dilution assays were performed to test the susceptibility of C. difficile and other anaerobes to Myxopyronin B, proving that the natural product is considerably active against C. difficile and that there is no cross-resistance between Fidaxomicin and Myxopyronin B in a Fidaxomicin-resistant C. difficile strain. Moreover, mass spectrometry analysis indicated that Myxopyronin B is able to suppress early phase toxin synthesis in C. difficile to the same degree as Fidaxomicin. Conclusively, Myxopyronin B is proposed as a new lead structure for the design of novel antibiotics for the therapy of C. difficile infections.

A Healing Promotion Wound Dressing with Tailor-made Antibacterial Potency employing piezocatalytic processes in multi-functional nanocomposites

Developing novel antibiotics-free antibacterial strategy is essential for minimizing bacterial resistance. Materials not only kill bacterial but also promote tissue healing are especially challenging to achieve. Inspired by chemical conversion...

Multi-omic characterisation of Streptomyces hygroscopicus NRRL 30439: detailed assessment of its secondary metabolic potential

The emergence of multidrug-resistant pathogenic bacteria creates a demand for novel antibiotics with distinct mechanisms of action. Advances in next-generation genome sequencing promised a paradigm shift in the quest to...

Bacterial Lipoprotein Posttranslational Modifications. New Insights and Opportunities for Antibiotic and Vaccine Development

Lipoproteins are some of the most abundant proteins in bacteria. With a lipid anchor to the cell membrane, they function as enzymes, inhibitors, transporters, structural proteins, and as virulence factors. Lipoproteins activate the innate immune system and have biotechnological applications. The first lipoprotein was described by Braun and Rehn in 1969. Up until recently, however, work on lipoproteins has been sluggish, in part due to the challenges of handling proteins that are anchored to membranes by covalently linked lipids or are membrane integral. Activity in the area has quickened of late. In the past 5 years, high-resolution structures of the membrane enzymes of the canonical lipoprotein synthesis pathway have been determined, new lipoprotein types have been discovered and the enzymes responsible for their synthesis have been characterized biochemically. This has led to a flurry of activity aimed at developing novel antibiotics targeting these enzymes. In addition, surface exposed bacterial lipoproteins have been utilized as candidate vaccine antigens, and their potential to act as self-adjuvanting antigens is increasingly recognized. A summary of the latest developments in lipoproteins and their synthesis, as well as how this information is being exploited for therapeutic purposes is presented here.

Discarded old antibiotics as a new arsenal for multi-resistant isolates in diabetic foot ulcer infections: therapeutic value of parenteral colistin versus multi-resistant Pseudomonas species isolate strains: case report

Antimicrobial resistance to current novel antibiotics is posing a major threat to both human and zoonotic life. In the absence of new novel antibiotics molecules, clinicians have resorted into a desperate last resort to review and re-introduce prior discarded antibiotics as their new weaponry in the fight against multi-resistant gram negative bacteria. We reported a case of a 77 year old bed ridden diabetic and hypertensive with renal impairment diagnosed with bilateral lower limbs wet gangrene. She underwent transfemoral on her right and transtibial amputation on her left lower limb. She developed surgical site infection on her right stump and wet gangrene on her left stump. Pus swab on her right stump revealed carbapenem resistant strains of Pseudomonas aeruginosa. She was instituted on parenteral colistin and showed no bacterial growth 7 days post treatment. She suffered an ischaemic cerebral vaso-occlusive stroke during her hospital stay. CT angiography of lower lung fields showed a large filling defect in the right main pulmonary artery extending to the lower lobe branches suggestive of right-sided pulmonary embolism. Our patient succumbed from her co-morbidities. Despite our patient succumbing to her multiple co-morbidities we reported this case to highlight the isolation of carbapenem resistant strains of P. aeruginosa and the efficacy and safety of colistin as a salvage antibiotic in renal impaired patients. Colistin can be safely used as a last reserve antibiotic for multi-resistant strains of P. aeruginosa infection even in patients with renal impairment.

Streptomyces, Greek Habitats and Novel Pharmaceuticals: A Promising Challenge

Bacteria of the genus Streptomyces produce a very large number of secondary metabolites, many of which are of vital importance to modern medicine. There is great interest in the discovery of novel pharmaceutical compounds derived from strepomycetes, since novel antibiotics, anticancer and compounds for treating other conditions are urgently needed. Greece, as proven by recent research, possesses microbial reservoirs with a high diversity of Streptomyces populations, which provide a rich pool of strains with potential pharmaceutical value. This review examines the compounds of pharmaceutical interest that have been derived from Greek Streptomyces isolates. The compounds reported in the literature include antibiotics, antitumor compounds, biofilm inhibitors, antiparasitics, bacterial toxin production inhibitors and antioxidants. The streptomycete biodiversity of Greek environments remains relatively unexamined and is therefore a very promising resource for potential novel pharmaceuticals.

Cyclohexyl-griselimycin is active against Mycobacterium abscessus in mice

Cyclohexyl-griselimycin is a preclinical candidate for tuberculosis (TB). Here, we show that this oral cyclodepsipeptide is also active against the intrinsically drug resistant non-tuberculous mycobacterium Mycobacterium abscessus in vitro and in a mouse model of infection. This adds a novel advanced lead compound to the M. abscessus drug pipeline and supports a strategy of screening chemical matter generated in TB drug discovery efforts to fast track the discovery of novel antibiotics against M. abscessus .

Antibiotic and novel compounds manipulation in vitro collagen matrix cells changes extracellular matrix non-complete cell division of fibroblast cells as new dermology technology

Fibroblasts are several cells that are essential for human skin function and regulation process, the underfeed cells are a further issue of skin disorder the current study was based on isolated novel antibiotics compounds comparison of (Chloramphenicol IV) with the changes of Extracellular matrix (RC), inflammatory cells (SC) and non-complete cell division (ICD) effects on fibroblasts cell changes with the cell wall in structural and morphological changes. The new antibiotic compounds were measured and characters in (FTIR) methods with their functional group's analysis of bioactive compounds from Adhatoda vasica and Calotropis procera plants and their effective inhibition concentrations (I C50) extract's against tyrosinase conditions with their activity in vitro enzymatic process, both extracts have higher enzymatic inhibition assay was assessed. The fibroblast cells were compared with Chloramphenicol IV antibiotics with extracted compounds the cell wall was indiscretion and complete shape and structural changes were measured. The higher values of Diphenolase (22.5 μg/mL) was noted in Adhatoda vasica while an IC50 value of Monophenolase was 19.16 μg/mL, which is helpful in the treatment of fibroblast cell disorders, were higher in collagenase inhibition assay, elastase inhibition assay, hyaluronidase inhibition assay, tyrosinase inhibition assay process. It was concluded that novel antibiotics compounds from species could act an as effective role in fibroblast were used in future medicines as sources of locations and creams to control various skin diseases and skin disorder management's processes.