Metabolic shift of Staphylococcus aureus under sublethal dose of methicillin in the presence of glucose.

Traditional strategies in developing novel drugs to treat antibiotic-resistant S. aureus have not been very successful to date, therefore, there is an urgent need for creative usage of existing agents that can treat and control S. aureus infection. This study demonstrated that a combination of glucose and a sublethal dose of antibiotic can reduce the survivability of S. aureus in a glucose concentration-dependent manner. Mass spectrometry-based targeted metabolic profiling detected massive metabolic profile shift of both methicillin-susceptible and resistant S. aureus after methicillin and glucose co-treatment. The dramatic alteration of metabolites from these metabolic pathways can be detected when 10 mg/L or higher concentration of glucose were added to methicillin treated culture. Our data also indicated that multiple biochemical metabolic pathways, including pyrimidine metabolism and valine, leucine, and isoleucine degradation showed a significant difference (p < 0.01) in comparison of control groups to glucose treatment groups. Taken together, this pilot study suggested that exogenous glucose in combination with a sublethal dose of antibiotics can disturb the metabolism of both methicillin-susceptible and resistant S. aureus, and enhance the antibiotic bactericidal effect.

Comparing the impact of ultrafine particles from petrodiesel and biodiesel combustion to bacterial metabolism by targeted HPLC-MS/MS metabolic profiling.

Alterations of gut bacterial metabolism play an important role in their host metabolism, and can result in diseases such as obesity and diabetes. While many factors were discovered influencing the gut bacterial metabolism, exposure to ultrafine particles (UFPs) from engine combustions were recently proposed to be a potential risk factor for the perturbation of gut bacterial metabolism, and consequentially to obesity and diabetes development. This study focused on evaluation of how UFPs from diesel engine combustions impact gut bacterial metabolism. We hypothesize that UFPs from different type of diesel (petrodiesel vs. biodiesel) will both impact bacterial metabolism, and the degree of impact is also diesel type-dependent. Targeted metabolic profiling of 221 metabolites were applied to three model gut bacteria in vitro, Streptococcus salivarius, Lactobacillus acidophilus and Lactobacillus fermentum. UFPs from two types of fuels, petrodiesel (B0) and a biodiesel blend (B20: 20% soy biodiesel/80% B0 by volume), were exposed to the bacteria and their metabolic changes were compared. For each bacterial strain, metabolites with significantly changed abundance were observed in both perturbations, and all three strains have increased number of altered metabolites detected from B20 UFPs perturbation in comparison to B0 UFPs. Multivariate statistical analysis further confirmed that the metabolic profiles were clearly different between testing groups. Metabolic pathway analyses also demonstrated several important metabolic pathways, including pathways involves amino acids biosynthesis and sugar metabolism, were significantly impacted by UFPs exposure.

Staphylococcus aureus methicillin resistance detected by HPLC-MS/MS targeted metabolic profiling.

Recently, novel bioanalytical methods, such as NMR and mass spectrometry based metabolomics approaches, have started to show promise in providing rapid, sensitive and reproducible detection of Staphylococcus aureus antibiotic resistance. Here we performed a proof-of-concept study focused on the application of HPLC-MS/MS based targeted metabolic profiling for detecting and monitoring the bacterial metabolic profile changes in response to sub-lethal levels of methicillin exposure. One hundred seventy-seven targeted metabolites from over 20 metabolic pathways were specifically screened and one hundred and thirty metabolites from in vitro bacterial tests were confidently detected from both methicillin susceptible and methicillin resistant Staphylococcus aureus (MSSA and MRSA, respectively). The metabolic profiles can be used to distinguish the isogenic pairs of MSSA strains from MRSA strains, without or with sub-lethal levels of methicillin exposure. In addition, better separation between MSSA and MRSA strains can be achieved in the latter case using principal component analysis (PCA). Metabolite data from isogenic pairs of MSSA and MRSA strains were further compared without and with sub-lethal levels of methicillin exposure, with metabolic pathway analyses additionally performed. Both analyses suggested that the metabolic activities of MSSA strains were more susceptible to the perturbation of the sub-lethal levels of methicillin exposure compared to the MRSA strains.