Induced antibiotic resistance and staphyloxanthin as a prospective target for treatment against pathogenic antibiotic-resistant staphylococci

Abstract

The past century saw the discovery of antibiotics as an effective treatment for bacterial infections. Life-threatening infections that were previously untreatable could now be neutralized by antibiotics with few side effects. However, in recent years this once effective treatment has become less efficient as the bacteria it once treated are becoming increasingly resistant. Antibiotic resistance presents a major concern in human public health not just on a national level, but potentially at a global level. The development of bacterial resistance to antibiotics is a natural response to stress. Plants have always been an important source of medicines and treatments. In cases where bacteria have become resistant to antibiotics, there have been notable successes in re-establishing antibiotic effectiveness when the antibiotics were used in combination with antibacterial plant extracts. The aim of this study was to compare the metabolites of an initially susceptible wild-type (WT) Staphylococcus with its mutated strain which had lost its antibiotic susceptibility. The mutated antibiotic resistant strain was made by exposing the susceptible WT strain to starvation stress. Metabolites from both strains were then extracted in methanol and analysed by 1H-NMR. Multivariate analyses of the NMR spectra showed significant differences in metabolites between the WT and resistant strains. LC-MS and GC-MS analyses of methanolic bacterial extracts showed that staphyloxanthin, a carotenoid that aids in pathogenesis and protects against oxidative stress was partially identified in low concentration from the WT strain. This was confirmed by comparing mass spectra with data on the NIST (National Institute of Standards and Technology) library database. The susceptible WT strain produced two staphyloxanthin precursors, compounds very similar to the two long chain parts of staphyloxanthin, while the resistant strain did not produce any detectable staphyloxanthin or its precursors. The precursors detected by GC-MS analysis and determined from the NIST Library were similar to squalene and tetradecanoic acid. These were the long hydrocarbon chains on the staphyloxanthin structure. This comparative model of analysing a WT and its consequently resistant strain could also be used as a platform to test the effectiveness of different plant treatments against bacterial defence mechanisms like staphyloxanthin. Focusing on the mechanisms of resistance without impeding bacterial growth might reduce the rate of adaptive resistance in-turn, thereby reducing the rate of antibiotic resistance during antibiotic therapy.