Staphylococcus aureus infections of the skin and soft tissue pose a major concern to public health, largely owing to the steadily increasing prevalence of drug resistant isolates. As an alternative mode of treatment both bacteriophage endolysins and bacteriocins have been shown to possess antimicrobial efficacy against multiple species of bacteria including otherwise drug resistant strains. Despite this, the administration and exposure of such antimicrobials should be restricted until required in order to discourage the continued evolution of bacterial resistance, whilst maintaining the activity and stability of such proteinaceous structures. Utilising the increase in skin temperature during infection, the truncated bacteriophage endolysin CHAPK and the staphylococcal bacteriocin lysostaphin have been co-administered in a thermally triggered manner from Poly(N-isopropylacrylamide) (PNIPAM) nanoparticles. The thermoresponsive nature of the PNIPAM polymer has been employed in order to achieve the controlled expulsion of a synergistic enzybiotic cocktail consisting of CHAPK and lysostaphin. The point at which this occurs is modifiable, in this case corresponding to the threshold temperature associated with an infected wound. Consequently, bacterial lysis was observed at 37 °C, whilst growth was maintained at the uninfected skin temperature of 32 °C.

Antimicrobial resistance is becoming an ever-increasing threat for human health. Metal complexes and, in particular, those that incorporate bismuth offer an attractive alternative to the typically used organic compounds to which bacteria are often able to develop resistance determinants. Herein we report the synthesis, characterization, and biological evaluation of a series of homo-and heteroleptic bismuth(III) thiolates incorporating either one (BiPh 2 L), two (BiPhL 2 ), or three (BiL 3 ) sulfur-containing azole ligands where LH = tetrazolethiols or triazolethiols (thiones). Despite bismuth typically being considered a nontoxic heavy metal, we demonstrate that the environment surrounding the metal center has a clear influence on the safety of bismuth-containing complexes. In particular, heteroleptic thiolate complexes (BiPh 2 L and BiPhL 2 ) display strong antibacterial activity yet are also nonselectively cytotoxic to mammalian cells. Interestingly, the homoleptic thiolate complexes (BiL 3 ) were shown to be completely inactive toward both bacterial and mammalian cells. Further biological analysis of the complexes revealed the first insights into the biological mode of action of these particular bismuth thiolates. Scanning electron microscopy images of methicillin-resistant Staphylococcus aureus (MRSA) cells have revealed that the cell membrane is the likely target site of action for bismuth thiolates against bacterial cells. This points toward a nonspecific mode of action that is likely to contribute to the poor selectivity's demonstrated by the bismuth thiolate complexes in vitro. Uptake studies suggest that reduced cellular uptake could explain the marked difference in activity between the homo-and heteroleptic complexes.

A series of diphenyl mono-phosphinato bismuth complexes were synthesised to study the effect of ligand choice on antibacterial activity, mammalian cell toxicity, and their behaviour in Bi-nanocellulose composites for use as antibacterial materials.

As bacteria continue to develop resistance to our existing treatment options, antibiotic innovation remains overlooked. If current trends continue, then we could face the stark reality of a postantibiotic era, whereby routine bacterial infections could once again become deadly. In light of a warning signaled by the WHO, a number of new initiatives have been established in the hope of reinvigorating the antibiotic drug development pipeline. In this perspective, we aim to summarize some of these initiatives and funding options, as well as providing an insight into the predicament that we face. Using clinical trials data, company website information and the most recent press releases, a current update of the antibiotic drug development pipeline is also included.

Here, a reaction-based indicator displacement hydrogel assay (RIA) was developed for the detection of hydrogen peroxide (H 2 O 2 ) via the oxidative release of the optical reporter Alizarin Red S (ARS). In the presence of H 2 O 2 , the RIA system displayed potent biofilm inhibition for Methicillin-resistant Staphylococcus aureus (MRSA), as shown through an in vitro assay quantifying antimicrobial efficacy. This work demonstrated the potential of H 2 O 2 -responsive hydrogels containing a covalently bound diol-based drug for controlled drug release.